Aims: To report on the clinico-pathological features of a series of 12 intra-oral mucoepidermoid carcinomas showing exclusive intra-cystic growth. Methods and methods: All mucoepidermoid carcinomas diagnosed in the period 1990-2012 were retrieved, the original histological preparations were reviewed to confirm the diagnosis, and from selected cases, showing exclusive intra-cystic neoplastic component, additional sections were cut at 3 subsequent 200m intervals and stained with Hematoxylin-Eosin, PAS and Alcian Blue, to possibly identify tumor invasion of the adjacent tissues, which could have been overlooked in the original histological preparations. Also, pertinent findings collected from the clinical charts and follow-up data were analyzed. Results: We identified 14 intraoral mucoepidermoid carcinomas treated by conservative surgery and with a minimum follow up of 5 years. The neosplasm were located in the hard palate (9 cases), the soft palate (2), the cheeck (2) and the retromolar trigone (1). In all instances histological examination was revealed the presence of a single cystic space, containing clusters of columnar, intermediate, epidermoid, clear and mucous-producing cells, the latter exhibiting distinct intra-cytoplasmic mucin production, as confirmed by PAS and Alcian Blue stains. The cysts were entirely circumscribed by fibrous connective tissue and no solid areas or infiltrating tumour clusters were detected. Conservative surgical resection was performed in all cases and no recurrences or nodal metastases were observed during the follow up period. Conclusions: Mucoepidermoid carcinomas showing prominent (>20%) intra-cystic proliferation currently are considered low-grade tumours. In addition, we also unveil the possibility that mucoepidermoid carcinomas, at least in their early growth phase, may display an exclusive intra-cystic fashion and might be considered as in situ carcinomas, unable to infiltrate adjacent tissues or metastasize.

The keratinocyte carcinomas, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

The human scalp is a common site of skin cancer in humans, with non-melanoma skin cancer being exceedingly common. In this review, two dermatologists with extensive experience in cutaneous oncology will discuss unique features of the epidemiology of cancer of the scalp. Clinical observations on these common skin cancers lead to insight into the pathogenesis and potential prevention and treatment of cutaneous scalp neoplasia. Our hypothesis is that the presence of hair protects against the development of skin cancer, but not by serving as a physical shield, but rather by providing a continuous IL-17 biased immunosurveillance. Loss of hair allow release from immunosurveillance, resulting in expansion of neoplastic cells towards skin cancer. Both hair follicles and metabolic changes in stroma allow permissiveness for tumor promotion.

The classification of kidney tumors has undergone a remarkable evolution since the early 19th century, reflecting advances in medical science and technology. This historical overview traces the development of renal tumor classification, beginning with early clinical observations and macroscopic descriptions to the integration of molecular diagnostics in contemporary classifications. The establishment of international organizations like the World Health Organization (WHO) facilitated collaboration and standardization in tumor classification, leading to refined classifications and standardized nomenclature. Advancements in histological and molecular studies, particularly genetic analyses, revolutionized the understanding of renal cell carcinomas, enabling precise categorization based on molecular characteristics. The journey from rudimentary classifications to sophisticated systems based on detailed histological, immunohistochemical, and molecular criteria underscores the continuous evolution of kidney tumor classification. This article provides a comprehensive overview of this evolution, highlighting the contributions of scholars and the impact of technological advancements on our understanding and management of kidney tumors.

Anaplastic thyroid cancer (ATC) is considered to be one of the most virulent, treatment refractory, malignancies. Recent molecular insights into the biology of thyroid cancer have transformed ATC management and BRAF/MEK targeted therapy is now incorporated into guideline based multidisciplinary care. We report visceral perforation in the setting of an extreme response to such therapy in a patient with a mixed papillary thyroid carcinoma and ATC. Molecularly targeted therapy afforded a dramatic, but life-threatening, response to treatment. This report highlights the complexities of care for the patient and treating clinicians.

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment, and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines, and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with the practical expertise in the oncological field. The article also includes two emblematic clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements of tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity.

In the most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when they present with classic infiltrative growth pattern. However, subset of IDC can occur in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it’s much easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Here, we reported a 55 year-old female who was noted to have microcalcification at the 11:00 o’clock of the right posterior breast on routine mammographic examination in 09/2023. Biopsy of the calcification area in 10/2023 reported high grade DCIS (ER+ PR-). Histologic examination of subsequent mastectomy specimen showed two separate DCIS-looking areas (Figure 1A-D and Figure 2). Immunohistochemical (IHC) staining showed that myoepithelial markers, smooth muscle myosin heavy chain (SMMHC), p63, CK5/6 and S100, were retained at the periphery of all the expanded acini in one area (Figure 1E-H). Unexpectedly and surprisingly, myoepithelial markers were completely lost at the periphery of part of the DCIS-looking acini in another area (Figure 3A-H), immunohistochemically compatible with the diagnosis of invasive ductal carcinoma admixed with DCIS. Knowing that invasive ductal carcinoma of the breast can present as DCIS-looking morphology, especially given the condition that the diagnosis of DCIS was rendered on the previous biopsy, will enhance awareness of pathologists to recognize DCIS-looking invasive ductal carcinoma. In turn, this will prevent misdiagnosis and under-treatment of patients with invasive ductal carcinoma of the breast.

Mitochondrial production of 2-hydroxyglutarate (R-2HG) can be catalyzed by wild-type isocitrate dehydrogenase 2 (IDH2) and alcohol dehydrogenase, iron-containing 1 (ADHFE1). We investigated whether biochemical background and substrate concentration in breast cancer cells promote 2HG production. To estimate its role in 2HG production, we analyzed 2HG levels and its enantiomers in breast cancer cells using analytical approaches for metabolomics. By manipulation of mitochondrial substrate fluxes, including glutaminolysis, using genetic and pharmacological approaches we demonstrated the existence of an active competition between 2HG producing enzymes, i.e. IDH2 and ADHFE1. Moreover, we show that distinct fractions of IDH2 enzyme molecules operate in distinct oxido-reductive modes, providing NADPH and producing 2HG simultaneously. We have also detected 2HG release into breast cancer patient´s urine undergoing adjuvant therapy and detected a correlation with stages of breast carcinoma development. In summary, we provide a background for vital mitochondrial production of 2HG in breast cancer cells with outcomes towards cancer biology and possible future diagnosis of breast carcinoma.

: Plant-derived terpenes have aroused considerable interest as chemotherapeutic agents for a variety of diseases. This study aimed at the isolation and purification of the scarce terpenes psiadin, plectranthone and saudinolide from their respective plants, followed by the determination of antiproliferative activity, against hepatic cancer cell lines (HepG2, Hep3B), and the potential molecular mechanisms. Time- and dose-dependent cytotoxicity, evaluated using MTT and colony-forming assays, were exhibited by psiadin and plectranthone against the cancer cells. Flow cytometry showed that these two terpenes blocked cell cycle progression and induced mitochondrial-mediated apoptosis, particularly through increased cytochrome c and disruption of mitochondrial membrane potential. Additionally, they initiated the generation of reactive oxygen species as well as inhibiting NF-B. Psiadin lowered several essential cyclins and cyclin-dependent kinases and reduced RB activation. It was concluded that psiadin, in particular, has a significant therapeutic potential with the biggest advantage of differentiating between cancer and normal cells which is acutely lacking in current cytotoxic drugs. Its precise mode of action needs further investigation but appears predominantly to cause cell cycle arrest by interfering with cyclin production. It will be important to determine, in future studies, whether these terpenes will similarly inhibit other cancer cell lines and retain its activity against tumors in vivo.

Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied fifteen patients affected by HCC undergoing LR and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and 5 with healthy liver) were used as controls. After LR, HCC patients were followed-up for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p<0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p=0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+) were not associated with HCC, neither could predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.

Background and Objectives: Renal cell carcinomas and upper tract urothelial carcinomas are types of malignancies that originate in the kidneys. Each of these examples shows an increasing trend in the frequency and the mortality rate. This study aims to comprehensively define carcinomas by analysing clinical, paraclinical, and histological aspects to predict aggressiveness and mortality. Materials and Methods: We conducted a retrospective investigation on a group of patients suspected with kidney cancers. Results: We identified 188 cases. We observed a higher mortality rate and older age in individuals with urothelial carcinomas. Anemia, acute kidney injury, hematuria and perineural invasion were the main risk factors that predicted their mortality. Tumour size in renal cell carcinomas correlates with the presence of necrosis and sarcomatoid areas. Factors that indicate a higher rate of death are older age, exceeding of the renal capsule, the lesion that includes the entire kidney, lymphovascular invasion, acute kidney injury, and anemia. Conclusions: Even if they originate at the renal level, and the clinical-paraclinical picture is similar, the histopathological characteristics make the difference. In addition, to these are added the previously mentioned common parameters that can represent important prognostic factors. In conclusion, the characteristics commonly identified in one type of cancer may act as risk factors for the other tumor. The detected data include threshold values and risk factors, making a significant contribution to the existing literature.

The metastatic disease is a complex and sequential process that involves the migration of tumor cells from the primary site to distant areas. This metastatic pathway is not always predictable. Therefore, this paper presents three rare cases of unusual metastases, due to their primary site: two metastases of a clear cell renal cell carcinoma, one gingival and one nasal, as well as a mandibular metastasis of a hepatocellular carcinoma. In all cases, an incisional biopsy was performed in order to sign out the diagnosis. After microscopical examination of morphological Hematoxylin and Eosin stained slides, for all cases, immunohistochemical reactions were performed to support the primary tumor site. Two cases had a previous histopathological diagnosis of a primary tumor, while for the third case, the metastatic lesion represented the first manifestation of the neoplastic disease, with an unfavorable prognosis.

Recent data has shown a continued rise in the worldwide annual incidence and mortality rates of head and neck cancers. The present standard for diagnosis and monitoring for disease recurrence or progression involves clinical examination, imaging, and invasive biopsy techniques of lesions suspected of being malignant. In addition to limitations relating to cost, time, and patient discomfort, these methodologies have inherent inaccuracies for detecting recurrence. In view of these limitations, the analysis of patient bodily fluid samples via liquid biopsy proposes a cost-effective and convenient alternative, which provides insight on the biogenetic and biomolecular underpinnings of oncologic disease processes. Liquid biopsy’s monitoring for biomarkers of head and neck cancer, including circulating tumor DNA, circulating tumor cells, and circulating cell-free RNA, has shown clinical utility in the screening, diagnosis, prognostication, and monitoring of patients with various forms of head and neck cancer. The present review will provide an update on the current literature examining the use of liquid biopsy in head and neck cancer care and the clinical applicability of potential biomarkers, with a focus on viral and non-viral circulating tumor DNA. Possible future avenues for research to address specific shortcomings of liquid biopsy will be discussed.

Background: We investigated the significance of the para-aortic node (PALN) and other regional node metastases (RLN), reflecting malignant histological findings or poor patient prognosis, in patients with biliary duct cancers (BDC) and pancreatic carcinomas (PC) who underwent radical resections at two institutes. Methods: Conventional clinicopathological factors, including metastasis to the PALN and RLN, and surgical outcomes or long-term prognosis in 181 PC and 116 BDC patients between 1994 and 2022 were examined. Results: In patients with PC, cancer metastasis was observed in the RLN and PALN in 54% and 9% of patients, respectively. In patients with BDC, cancer metastasis was observed in the RLN and PALN in 39% and 9% of patients, respectively. Disease-free survival (DFS) and overall survival (OS) in patients with BDC and PALN metastasis were significantly lower than those without PALN metastasis; however, several patients survived over three years. Multivariate analysis revealed that, in patients with BDC, PALN metastasis was an independently related factor of OS, and RLN was an independently related factor for DFS, respectively (p

Background: Metastatic tumors to the oro-facial tissues are rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5th–7th decades, but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patient with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon-rectum in males, or uterus, breast, lung, and ovary in females. In the oro-facial tissues the sites mostly involved are the oral mucosa, gingiva/jawbones, tongue, and the salivary glands. Methods: A systemic Review of the literature on the oro-facial metastases from Renal Cell Carcinoma has been conducted by searching the most used databases, also focusing the attention on the Clear Cell histological variant, representing the most frequent one. Results: Among the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found (148 in males, 70.1%; 63 in females, 29.8%), with an average age of 59.8 years. In almost 40% of cases, metastasis represented the first clinical manifestation of the primary tumor and 122 were histologically diagnosed as ccRCCs (57.8%). The tongue was involved in most of the cases (26% - 55 cases), followed by mandible (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxilla (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Among the 122 ccRCCs (84 were males, 68.8 %; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most involved site (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14 cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases), lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). The clinical presentation in soft tissues was represented by a fast-growing exophytic mass, sometimes accompanied by pain. Instead inn bone appeared as radiolucent lesions, with ill-defined borders and cortical erosion. Conclusions: Our data focus the attention on the incidence of Renal cancer Metastases in the oro-facial tissues. Their early identification surely represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico-facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key for better outcomes. Therefore, general guidelines about clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentists.

Background: We aimed to create a model of radiological and pathological criteria able to predict the upgrade rate of low-grade ductal carcinoma in situ (DCIS) to invasive carcinoma, in patients undergoing vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. Methods: 3100 VABBs were retrospectively reviewed among which we reported 295 low-grade DCIS who subsequently underwent surgery. The association between patients’ features and the upgrade rate to invasive breast cancer (IBC) was evaluated by univariate analysis. Finally, we developed a predictive multivariable model based on the features which were significantly associated with the univariate analysis outcome. Results: the upgrade rate to invasive carcinoma was 10.8 %. At univariate analysis, the risk of upgrade was significantly lower in the absence of post- biopsy residual lesion (p<0.001), age > 50 (p=0.029), and in presence of low-grade DCIS only in specimens with microcalcifications (p=0.002). According to the final multivariable model, the predicted probability of diagnostic underestimation for a patient with all the three favourable features selected at univariate analysis was 1% (95% CI: 0.3%-4%). Conclusions: An easy to use predictive model of radiological and pathological criteria is able to identify patients with low-grade carcinoma in situ with low risk of upstaging to infiltrating carcinomas.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, and most of them recur within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment and prognosis in patients with HNSCC are associated, investigations are insufficient. In this study, patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n = 500). A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing early recurrence (ER) (recurrence within 2–6 months) and late recurrence (LR) (recurrence after 7 months), respectively. There were two independent risk factors for poor prognosis in the multivariate analyses: ER (hazard ratio [HR] = 3.200, 95% confidence interval [CI] = 1.570–6.521, p = 0.001) and no radiotherapy (HR = 0.374, 95% CI = 0.191–0.733, p = 0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in patients. During the selection of treatment for patients with recurrence, the recurrent area, initial treatment content, and strategy of changing salvage therapy depending on the recurrence status should be considered.

This report elucidates a case of papillary carcinoma of the Thyroglossal Duct Cyst in a 19-year-old female. The swelling at presentation was suprahyoid, fixed and non-mobile with deglutition or tongue protrusion. Papillary carcinoma was diagnosed post-op through histopathological examination and a follow-up total thyroidectomy was planned. As the origin of TGDC papillary carcinoma is highly debated, no evidence-based guidelines yet exist as to the best line of treatment, however, Sistrunk’s procedure followed by total/near total thyroidectomy is widely considered the standard management practice in such cases.

In this study, novel biomarkers in Blood Mononuclear Cells (PBMCs) of Hepatocellular Carcinoma (HCC) patients were identified through microarray data analysis. The problem that prompted the study was the lack of reliable biomarkers for early diagnosis and monitoring of HCC. The purpose of this study was to discover potential biomarkers in PBMCs of HCC patients that can be used for early diagnosis and monitoring of the disease. The main hypothesis was that there are genes that are overexpressed in PBMC of HCC patients compared to healthy individuals. The results showed that genes HBB, WBP2, HBA2, and HBA1 were overexpressed in PBMCs of HCC patients. Additionally, nine genes were found to be upregulated in HCC patients and had a relation between KEGG pathways of RA, suggesting a link between the two diseases. These genes are TLR4, IL1B, CXCL5, IL11, HLA-DQA1, HLA-DRA, LBT, ATP6V1B2 and ATP6V1C1. The Gene ontology analysis revealed biological processes used in the process of how these genes play a role in development of HCC. In conclusion, this study identified potential biomarkers in PBMC of HCC patients that can aid in early diagnosis and monitoring of the disease. The findings of this study have important implications for improving the clinical management of HCC patients.

Background: Hepatocellular carcinoma (HCC) is a global health problem associated with chronic liver disease. The pathogenesis of chronic liver disease varies according to the underlying etiological factor, although in most cases it develops from a liver cirrhosis. The worsening progression of liver disease is accompanied by pathological angiogenesis, which is a prerequisite that favors the development of HCC. The aim of this study is to evaluate the clinical utility of circulating angiogenic markers VEGF, Ang-1, Ang-2, the Angiopoietin receptor (Tie1/2), HGF and PECAM-1 to screen early onset patients and to follow the evolution of HCC. Materials and Methods: We enrolled 62 patients; 33 out of 62 subjects were diagnosed for HCC and 29/62 for liver cirrhosis of different etiology without signs of neoplasia. Patients underwent venous blood sampling before and after treatments for VEGF, Ang-1, Ang-2, Tie1, Tie2, HGF and PECAM-1 measurement. Results: Ang-1 and Ang-2 are detectable not only in patients already suffering from HCC but also in cirrhotic patients without signs of cancer. Patients with HCC show higher HGF concentrations than patients with cirrhosis. A significant reduction in serum levels of Ang-2, Ang-2/Ang-1 and Ca 19-9 after DAAs therapy was observed. Moreover, VEGF levels were increased after treatment of HCC. Conclusion: The preliminary study here presented confirms that the mechanism of tumor angiogenesis is very complex and involves a very large number of factors. The integration of different methodologies and multi-marker algorithms is likely to emerge for the early diagnosis of HCC and the monitoring of the risk of relapse.

Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing. However, the detailed mechanisms of NK cell dysfunction in tumor microenvironment of HCC remain largely unknown. A better understanding of the mechanisms of NK cell dysfunction in HCC will help in the NK cell-mediated eradication of cancer cells and prolong patient survival. In this review, we describe the various mechanisms underlying NK cell dysfunction in HCC. Further, we summarize current advances in the approaches to enhance endogenous NK cell function and in adoptive NK cell therapies, to cure this difficult-to-treat cancer.

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are highly prevalent and a significant cause of morbidity. Image-guided su-perficial radiation therapy (IGSRT) uses integrated high-resolution dermal ultrasound to improve lesion visualization, but it is unknown whether efficacy varies by histology. This large retro-spective cohort study was conducted to determine the effect of tumor histology on freedom from recurrence in 20,069 biopsy-proven NMSC lesions treated with IGSRT, including 9,928 BCC (49.5%), 5,294 SCC (26.4%), 4,648 SCCIS (23.2%), and 199 lesions with ≥2 NMSCs (1.0%). Freedom from recurrence at 2, 4, and 6 years was 99.60%, 99.45%, and 99.45% in BCC; 99.58%, 99.49%, and 99.49% in SCC; and 99.96%, 99.80%, and 99.80% in SCCIS. Freedom from recurrence at 2, 4, and 6 years following IGSRT did not differ significantly comparing BCC vs. non-BCC or SCC vs. non-SCC but were slightly lower among SCCIS vs. non-SCCIS (p = 0.002). There were no significant differences in freedom from recurrence when stratifying lesions by histologic subtype. This study demonstrates that there is no significant effect of histology on freedom from recurrence in IGSRT-treated NMSC except in SSCIS. These findings support IGSRT as a first-line therapeutic option for NMSC regardless of histology.

Novel ZNF proteins such as ZNF671 that are located on chromosome 19q13 are known to be hypermethylated at a high frequency in HNSCC as well as in other epithelial solid tumors. Their function is largely unknown. Here, we show that ZNF671 is epigenetically silenced in HNSCC primary tumors compared to matched adjacent normal tissue. Moreover, low expression of ZNF671 is significantly associated with decreased survival in HNSCC patients. Over-expression of ZNF671 in UM-SCC-1 oral cancer cells resulted in a significant reduction in tumor cell mobility and invasion compared to the empty-vector control cells. Transcriptomic analysis showed that ZNF671 re-expression resulted in a significant decrease in the expression of a major oncogenic long non-coding RNA LINC00665. Together, these results suggest that epigenetic silencing of ZNF671 may activate multiple oncogenic signaling pathways via the resulting up-regulation of LINC00665.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

Introduction: In recent years, generative Artificial Intelligence models, such as ChatGPT, have been increasingly utilized in healthcare. Despite acknowledging the high potential of AI models in terms of quick access to sources and formulating a response to a clinical question, the results obtained using these models still require validation through comparison with established clinical guidelines. This study compares the responses of the AI model to eight clinical questions with the Italian Association of Medical Oncology (AIOM) guidelines for ovarian cancer. Materials and Methods: The authors used the Delphi method to evaluate responses from ChatGPT and the AIOM guidelines. An expert panel of healthcare professionals assessed responses based on clarity, consistency, comprehensiveness, usability, and quality using a 5-point Likert scale. The GRADE methodology assessed the evidence quality and the recommendations' strength. Results: A survey involving 14 physicians revealed that the AIOM guidelines consistently scored higher averages compared to the AI models with a statistically significant difference. Post-hoc tests showed that AIOM guidelines significantly differed from all AI models, with no significant difference among the AI models. Conclusions: While AI models can provide rapid responses, they must match established clinical guidelines regarding clarity, consistency, comprehensiveness, usability, and quality. These findings underscore the importance of relying on expert-developed guidelines in clinical decision-making and highlight potential areas for AI model improvement.

Bone is the second most frequent site of metastases from differentiated thyroid carcinoma (DTC). Bone metastases (BM) occurs in about 10% of all patients with DTC. They are more frequently observed in follicular thyroid carcinoma (FTC) (7-28%), than in thyroid papillary carcinoma (PTC) (1-7%) [1,2] and are associated to unfavorable clinical out-comes, mainly related to skeletal related events (SREs), such as pathologic fractures, bone pain, spinal cord compressions and hypercalcemia, which impair the quality of life and reduce life expectancy. BM from DTC require multimodal and comprehensive treatment, including radioiodine therapy (RAI), palliative treatment, surgical treatment, external beam radiation and target drug therapy. RAI is the first line treatment, but about two thirds of DTC patients with distant metastases are not definitively cured. This treatment is considered less effective in BM particularly in case of large metastases. The different response to RAI treatment alone or associated to BM focal treatment depends to RAI avidity of lesions [3]. We report the rare case of an excellent response to RAI of a metachronous bone metastasis of skull from FTC, in a 72 yrs old woman, diagnosed 15 years after the first treatment, followed by a complete regression of radioiodine up-taking area with persistence of excellent response to the treatment six years after it. This case confirms that the complete BM response to RAI treatment depends to the degree of dedifferentiation of cancers cells and enforce the concept of a long- life follow-up of FTC patients.

The study explored the correlation between serum biomarkers and hepatocellular carcinoma detection in various fishing groups, utilizing a descriptive and experimental approach in Bangladesh. The study identified fishers often consume tobacco, polluted drinking water, and lack sufficient sunlight, all of which are extremely detrimental to their health. Fishermen who mostly fish at night and spend little time on the water during the daytime hours do not get enough sunlight, nor do they get enough vitamin D. An increased risk of liver cancer was found to be directly and strongly correlated with insufficient serum levels of vitamin D. In addition, a negligent lifestyle, a lack of awareness about hepatitis, and inadequate nutritional assistance have significantly increased their risk. Our results contribute to the information on HCC assessment and evaluation by clarifying the relevance of serum vitamin D, alpha-fetoprotein (AFP), creatinine (Cr), and hemoglobin A1C (HbA1c) in distinguishing between categories and sexes. According to the study, the combination of AFP, Vitamin-D, and Cr (AFP+Vit-D+Cr) has a high predictive value, which improves diagnosis and offers a reliable instrument for identifying liver cancer.

This study aimed to establish a predictive model for neoadjuvant chemoradiotherapy (nCRT) response in patients with locally advanced rectal carcinoma (LARC) using clinicopathological (CP) features along with radiomics from pretreatment Magnetic Resonance Imaging (MRI) 3D T2W contrast sequence scans. The study also assessed the impact of radiomic dimensionality on predictive performance. Seventy-five patients were prospectively enrolled with clinicopathologically confirmed LARC who underwent nCRT before surgery. Tumor properties were assessed by calculating 2142 shape, first-order, and second-order radiomics features. Least absolute shrinkage and selection operator (LASSO) and multivariate regression were used for feature selection. Two predictive models were constructed, one using 72 CP and 107 radiomics features, and the other using 72 CP and 1862 radiomics features. The models revealed moderately advantageous impact of increased dimensionality, while their predictive performance was in the range generally considered excellent, with respective AUCs of 0.86 and 0.90. A CP-only model (AUC=0.80) served as the benchmark for predictive performance without radiomics. The predictive models developed in this study using pretreatment MRI data, radiomics features, and clinicopathological parameters could potentially be used to routinely predict chemoradiotherapy responders, enabling clinicians to personalize treatment strategies for rectal carcinoma.

Background – Endobronchial squamous cell carcinoma is one of the most common types of tumors with such a location. Patients often present in advanced stages of the disease, which leads to a targeted therapeutic attitude of pneumonectomy, most of the time. Practicing a lung parenchyma-preserving surgery led us to do this review. Material and Methods - We used three search platforms SCIENCE, MEDLINE and PubMed, in order to identify studies presenting case reports, studies and reviews on endobronchial squamous cell carcinoma. We identified clinical and paraclinical features of endobronchial squamous cell carcinoma. All selected articles were in English and contained clinical criteria of endobronchial squamous cell carcinoma, autofluorescence bronchoscopy in endobronchial squamous cell carcinoma, imaging features of endobronchial squamous cell carcinoma, blood tumor markers specific for lung squamous cell carcinoma, histopathological features of endobronchial squamous cell carcinoma. Results - 73 articles were analyzed, from which 47 articles were selected as bibliographic references. We have presented the criteria found for endobronchial squamous cell carcinoma in order to highlight the main characteristics and high reliability technologies for the detection of this type of cancer. Conclusions – The current literature review highlights the clinical and paraclinical characteristics of endobronchial squamous cell carcinoma. It aims to open new horizons for research and early detection, frequent practice of lung parenchymal preservation surgery.

Primary carcinomas of the lung are vastly represented by the conventional types of adenocarcinomas or squamous cell carcinomas. However, there are other types of non-small cell carcinomas that although uncommon represent a meaningful group that often pose a problem not only in diagnosis but also in classification. Spindle and giant cell carcinomas although uncommon primary lung carcinomas are well known to occur. Important to highlight is that current criteria are rather ambiguous and likely not up to date, which renders the classification of these tumors somewhat more obscure. In addition, with the daily use of immunohistochemical stains, the classification of these tumors may also pose a different problem in the proper allocation of these tumors. Proper classification is highly important in the selection process that takes place using such material for molecular analysis. Current molecular characteristics of these tumors is limited and lacks more in-depth studies and analysis that can provide specific targets for the treatment of patients with these tumors. The current review attempts to highlight the shortcomings in the current classification and definitions of these neoplasms as well as the more current view regarding these tumors when the use of immunohistochemical stains is employed.

Mesothelin is a protein that is expressed in the mesothelial cell lining in the pleura, peritoneum, and pericardium. The gene of mesothelin encodes a precursor protein that is processed to yield mesothelin, which is attached to the cell membrane by a glycophosphatidylinositol linkage and a shred fragment named the megakaryocytic-potentiating factor. The biological functions of this substance in normal cells are still unknown. Experimental studies on knockout mice suggest that this substance does not play an important role in development and reproduction. In contrast, it has been observed that mesothelin is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered a tumour marker or an antigenic target for many malignancies. Many molecular studies also have demonstrated that mesothelin is overexpressed in serous ovarian carcinomas and may bind to ovarian cancer antigen Ca-125, favouring the spread of the tumour in the abdominal cavity. 3 Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses as well as its impact on the prognosis in serous ovarian carcinomas. We also briefly discuss the latest progress of mesothelin-targeting therapies for this aggressive and lethal neoplasm.

Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.

Hepatocellular carcinoma (HCC) is a liver cancer that originates from hepatocytes. It is a primary health issue and one of the most common malignant tumors. The US FDA approved Sorafenib as the first-line anti-cancer drug for advanced HCC patients. A few patients with advanced HCC may benefit from Sorafenib treatment, but most of the patients eventually develop resistance to Sorafenib, which leads to its poor prognosis. Long-noncoding RNAs (lncRNA) have been found to play a critical role in tumorigenesis and the development of HCC, as well as various cancers. It also plays a vital role in tumor drug resistance, while the mechanisms of LncRNAs in HCC sorafenib resistance have not been characterized yet. In this review article, we summarized the molecular mechanisms, such as the involvement of transporters, receptors, cell death regulation, and other factors impacting sorafenib resistance in HCC.

Contrast-enhanced ultrasonography (CEUS) is useful for evaluation of the hemodynamics of hepatic tumors and surrounding he-patic parenchyma in real time. CEUS with intravenous contrast administration is well established for evaluation of hepatocellular carcinoma (HCC). On the other hand, intra-arterial (transcatheter) CEUS (IAUS) is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. IAUS was performed by administration of Sonazoid® through the microcatheter and imaging of the area of the target lesion with a dedicated, contrast-specific technique. Sonazoid® (0.5 ml diluted with 49.5 ml of distilled water) was used as the contrast medium in IAUS. The diluted Sonazoid® was introduced into the feeding artery by in-termittent injection of 0.3-1.0 ml through a microcatheter placed in the artery and flushing with saline at the same flow rate. We report the three cases in which IAUS was useful in transarterial chemoembolization (TACE) for HCC. Two cases were performed TACE for hepatic metastasis. In any cases, plain computed tomography (CT) after TACE showed accumulation of Lipiodol® only in the metastases. One case was suspected having HCC rupture and urgent abdominal angiography was performed. IAUS was performed frequently to reduce the amount of iodinated contrast agent as much as possible because of renal failure. Concomitant use of IAUS enabled reduction of the amount of contrast agent.

Chondroitin sulfate (CS) proteoglycan 4 (CSPG4) is a cell surface proteoglycan that is currently under investigation as a marker of cancer malignancy, and as a potential target of anticancer drug treatment. CSPG4 acts as a driver of tumourigenesis by regulating turnover of the extracellular matrix (ECM) to promote tumour cell invasion, migration as well as inflammation and angiogenesis. While CSPG4 has been widely studied in certain malignancies, such as melanoma, evidence is emerging from global gene expression studies, which suggests a role for CSPG4 in squamous cell carcinoma (SCC). While relatively treatable, lack of widely agreed upon diagnostic markers for SCCs is problematic, especially for clinicians managing certain patients, including those who are aged or infirm, as well as those with underlying conditions such as epidermolysis bullosa (EB), for which a delayed diagnosis is likely lethal. In this review, we have discussed the structure of CSPG4, and quantitatively analysed CSPG4 expression in the tissues and pathologies where it has been identified. The aim of this review has been to collate the information available from functional studies and recent transcriptome analysis to determine the usefulness of CSPG4 expression as a diagnostic marker and therapeutic target in management of malignant SCC.

Salivary gland tumors are relatively rare neoplasms, comprising approximately 3-6% of all head and neck tumors. Parotid gland carcinoma (PGC) represents approximately 70-80% of all salivary gland malignancies. Treatment strategies depend on tumor histology, stage, and molecular characteristics, with surgical resection and adjuvant radiotherapy being the mainstays of treatment for localized disease. Conversely, in advanced stages therapeutic approaches, including chemotherapy and targeted agents, are more challenging. We present a case report of a 60-year-old patient with hepatic and nodal metastases of parotid gland’s carcinoma, with the aim of highlighting the management and treatment outcomes.

The increasing incidence of hepatocellular carcinoma (HCC) together with the poor effectiveness of the available therapeutic treatments, make an early diagnosis and an effective screening of utmost relevance. Liquid biopsy represents a potential novel approach for early HCC detection and monitoring. The identification of blood markers has many desirable features among which the absence of any significant risk for the patients, the possibility to be used as screening tool and to perform multiple tests thus allowing a real-time monitoring of HCC evolution. Unfortunately, the available blood markers of HCC have several limitations mostly related to specificity and sensitivity. In this context, the employment of non-coding RNAs (ncRNAs) may represent an interesting and novel diagnostic approach. ncRNAs which includes among others, micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), regulate human gene expression via the interaction with their target mRNA. Notably, their expression can be altered in HCC thus reflecting the diseased status. In this review, we discuss some noticeable works, which describe the use of miRNAs, lncRNAs and circRNA as HCC biomarkers. Despite some open aspects related to ncRNA use, the presented works strongly support the potential effectiveness of these molecules as diagnostic/prognostic markers for HCC.

Background Hepatic resection offers promising outcomes for patients with hepatocellular carcinoma (HCC) but can be constrained by factors like patient suitability. Continuous advancements in laparoscopic and robotic technologies have made minimally invasive hepatectomies (MIH) viable alternatives to open hepatectomies with benefits in recovery and complications. Materials and Methods We completed a retrospective review on 138 HCC patients at the Hume-Lee Transplant Center that underwent OH or MIH between 2010 and 2020. Univariate and multivariate analyses were completed on demographic, clinical, and tumor-specific data were collected to assess the impact of these variables on overall and disease-free survival at 1-, 3-, and 5-years. Preoperative metrics like length of hospital stay (LOS) and operation duration were also evaluated. Results Of the 109 OH and 29 MIH patients, MIH patients demonstrated shorter LOS and operative times. However, overall survival (OS) and disease-free survival (DFS) were similar between groups, with no significant variations in 1-, 3-, and 5-year survival rates. Ages > 60 years and lack of preoperative transcatheter arterial chemoembolization (TACE) were significant predictors of inferior OS and DFS in multivariate analyses. Conclusions MIH is an efficient substitute to OH with comparable survival even in older patients. The reduced LOS and operation time enhances its feasibility, and older patients previously denied for curative resection may qualify for MIH. Preoperative TACE also enhances survival outcomes, emphasizing its general role in managing resectable HCCs. Both robotic and laparoscopic hepatectomies offer acceptable short- and long-term clinical outcomes, highlighting MIH as the standard choice for HCC patients.

Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than pancreatic ductal adenocarcinoma. We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022. Patient information was extracted from our institutional database with the approval of Institutional Review Board. We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, 1 had borderline resectable disease, and 1 had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (1 patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases which had BostonGene tests was found to have NTRK1 fusion. RNA and TME analysis by BostonGene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74 and MMP1 and higher CDH6 compared with PDAC.

Liver cancer is the fourth leading cause of cancer-related death worldwide. In Mexico, there is a high burden of liver cancer mortality in rural states, which affects both women and men equally. Thus, we aimed to describe the demographic and clinical characteristics of hepatocellular cancer (HCC) by sex in Mexico. Demographic and clinical information were extracted retrospectively from the medical records of patients with HCC initially treated (2015-2022) at participating institutions of a national survey across the country. The male-to-female ratio was calculated at the national and regional levels and the results were stratified by sex. Among 697 HCC patients, the age at diagnosis was 65.4±11.9y and 20% were diagnosed at ≥75y. The male-to-female ratio was 1.4:1, ranging from 1:1 in the northwestern and southwestern regions to 2.1:1 in the western region. The proportion of cirrhosis was similar between sexes; however, the etiologies for cirrhosis differed: cryptogenic cirrhosis was higher in women and alcohol consumption was higher in men. Men had a higher proportion of advanced HCC, poor/undifferentiated tumors, and ≥4 nodules than women. HCC in the Mexican population affects men and women at a 1.4:1 male-to-female ratio. This unique proportion by sex could be explained by the differences in the prevalence of risk factors across our heterogeneous country.

Metabolic Associated Steatohepatitis Liver Disease (MASLD) currently impacts a quarter of the global population and its prevalence is expected to increase in the future. As a result, the incidence of hepatocellular carcinoma associated with MASLD is also on the rise. Notably, hepatocellular carcinoma in this group does not always develop alongside liver cirrhosis, often leading to a more advanced stage at diagnosis. The challenge lies in accurately identifying patients who are at a higher risk of hepatocellular carcinoma to tailor screening processes effectively. Additionally, several therapeutic approaches are being explored to prevent hepatocellular carcinoma, although there are yet no universally accepted guidelines

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is highly invasive and easily recurs. For HCC, chemotherapy shows a limited effect. The gold standard for HCC treatment includes curative surgical resection or liver transplantation. However, the recur-rence rate at 5 years after liver resection is estimated at approximately 70% and even at 5 years after liver transplantation, it is 20%. Therefore, improving survival outcomes after curative surgi-cal resection of liver cancer is crucial. This review highlights the importance of identifying risk factors for HCC recurrence following radical surgical resection and adjuvant therapy options that may reduce the recurrence risk and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization and radiotherapy), adjuvant systemic therapy (e.g., small molecule targeted therapy and immunotherapy), and other adjuvant therapies (e.g., chem-otherapy). However, further research is needed to refine the use of these therapies and optimize their effectiveness in preventing HCC recurrence.

To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus. At a median (interquartile range) follow-up of 4.4 (3.8) years after transplantation, everolimus patients showed a reduced risk of recurrence versus tacrolimus (7.7% versus 16.9%; RR=0.45; P=0.002). At multivariable analysis, microvascular infiltration (HR=1.22; P<0.04) and a higher tumor grading (HR=1.27; P<0.04) were associated with higher recurrence rate while being within Milan criteria at transplant (HR=0.56; P<0.001), a successful pre-transplant downstaging (HR=0.63; P=0.01) and use of everolimus (HR=0.46; P<0.001) had a positive impact on the risk of post-transplant recurrence. EVR patients with earlier drug introduction (30 days; P<0.001), longer treatment duration (P<0.001), and higher drug exposure (5.9ng/mL; P<0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction of the relative risk of hepatocellular carcinoma recurrence, especially for advanced-stage patients and those with earlier drug administration, higher drug exposure, and longer time on treatment. These data advocate for early everolimus introduction after liver transplantation to reduce the attrition rate consequent to chronic immunosuppression.

We present our preliminary experience with transarterial radioembolization (TARE) with Yt-trium-90, and investigate the influence of additional treatments, injected activity, mean dose to the tumor on overall survival (OS). Our database was interrogated to retrieve patients who had undergone TARE with Yttrium-90 (90Y) glass or resin microspheres. The following information were searched: 1) type of pathology; 2) sex; 3) age; 4) administered activity; 5) mean dose to the tumor; 6) additional treatments; 7) OS. The OS of the different groups of patients were compared (p<0.05). A bivariate correlation (p<0.05) was used to investigate the association between injected activity and OS, and between mean dose to the tumor on OS. Thirty-nine patients were retrieved (Sex: 27 M, 12 F; mean age: 61.26 ± 14.95 years): 23 with hepatocellular carcinoma (HCC) and 16 with colorectal cancer (CRC) liver metastasis. Globally, patients with HCC demonstrated a sig-nificantly longer OS than those with CRC liver metastasis (22.66±19.11 vs. 10.41±8.75 months; p=0.022). Among patients with CRC liver metastasis, those receiving TARE and additional treatment demonstrated a longer OS than patients receiving only TARE (23.50±19.76 months vs. 8.54±5.31; p=0.018), there was a direct correlation between injected activity and OS (R=0.55, p=0.034) and between mean activity reaching the tumor and OS (R=0.812; p=0.008). Patients with HCC receiving TARE achieved a longer OS than those with CRC liver metastasis. Additional treatments, increasing injected activity and higher mean dose to the tumor seem beneficial for outcome, especially in patients with CRC liver metastases.

The frequency of concurrent thyroid cancer in patients with primary hyperparathyroidism (pHPT) varies. While the pathological association between thyroid and parathyroid disorders is frequently noted, the co-occurrence of parathyroid adenoma and papillary thyroid cancer is exceptionally rare. Furthermore, the occurrence of an ectopic parathyroid adenoma in the retropharyngeal space is exceedingly rare. Ectopic parathyroid glands present considerable complexities in both diagnosis and surgical management, especially within the realm of surgical intervention. The potential inability to accurately identify and excise ectopic parathyroid adenomas during the initial surgery may lead to an increased morbidity and recurrence, requiring high-risk reoperations. Therfore, the evaluation of anatomical variations through the utilization of relevant diagnostic tools plays a crucial role in guiding decisions pertaining to clinical manifestations, diagnostic methods, surgical interventions, and operative strategies for parathyroid tumors. We present the case of a 51-year-old female patient with papillary thyroid carcinoma in the right thyroid lobe and an ectopic parathyroid adenoma in the retropharyngeal space confirmed through surgical intervention. This case sheds light on the unusual occurrence of an ectopic parathyroid adenoma in the retropharyngeal region within a thyroid cancer patient, providing valuable insights within the realm of thyroid malignancies.

Lipid dysregulation is critically involved in hepatocellular carcinoma (HCC). Further, male predi-lection and Ras pathway hyperactivation are distinct characteristics of HCC. However, mecha-nisms underlying their connections remain unknown. The aim of the present study was to perform a comprehensive lipidomics analysis of a Hras12V transgenic mice (Ras-Tg) model of HCC induced by hepatocyte-specific Ras pathway activation and characterized by male predilection and a dis-rupted lipid metabolism. A total of 3437 lipids were identified in HCC (T) and peri-tumor tissues (P) of Ras-Tg mice and liver tissues of wild-type mice (W) of both sexes. Longitudinal comparisons of W, P, and T yielded 359 differentially expressed lipids (DELs) in male mice and 306 DELs in female mice. Generally, glycerolipid accumulation, glycerophospholipid reduction and monounsaturated fatty acid synthesis improvement were more frequent in T compared to P. The expression change pattern analysis revealed common and characteristic DELs positively/negatively associated with HCC or the Ras oncogene. Further lipid metabolism pathway investigations revealed that disordered lipid and fatty acid biosynthesis contributed to glycerolipid accumulation and glycerophospholipid re-duction in T. Comparisons between P and W suggests that different responses to the Ras oncogene in mice of different sexes, as well as higher amounts of aberrantly regulated lipids in males, may contribute to male-biased hepatocarcinogenesis. However, lateral comparisons between sexes showed a converging trend during hepatocarcinogenesis, explaining the poor efficacy for gen-der-specific therapies. In conclusion, the common and characteristic DELs and lipid metabolism pathways in HCC initiated by the Ras oncogene from sexually dimorphic hepatocytes provide novel insights into the clinical diagnosis and management of HCC.

Introduction: Bone fractures may be the result of high force impact or stress, or a minimal trauma injury as a result of certain medical conditions that weaken the bones, such as osteoporosis, osteopenia, bone cancer, or osteogenesis imperfecta, where the fracture is then properly termed a pathologic fracture. Bone cancer can be primarily or secondary to metastasis. Case presentation: We report a rare case of left humerus fracture in a 59-year-old male patient due to metastatic renal cell carcinoma. Our patient had no important past medical history. He suffered from two months of left arm pain, moderate disability and fever at night. Analgesics consumption resulted in minimal relieve. Trauma history was negative. X-ray of the left arm showed an osteolytic lesion with humerus fracture. Abdominal computed tomography with contrast showed right renal mass.Radical right nephrectomy was performed in addition to alignment nailing of the left humerus fracture with biopsy. Pathology report documented clear cell carcinoma with metastatic bone. The treatment was completed by chemotherapyDiscussion: Secondary bone tumors are metastatic lesions which have spread from other organs, most commonly carcinomas of the breast, lung, and prostate, and rarely from kidney. In some cases, bone metastasis could be the first symptoms of renal cell carcinoma. Conclusion: suspected pathological bone fractures should be investigated completely. It may hide a tumor as a cause.

Background and aim We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). Methods A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. Results The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0–21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: ≤20 mm group (n=483), 20–30 mm group (n=107), and ≥30 mm group (n=17) (p<0.001). The cumulative local tumor recurrence rate was similar by difficult-to-treat status (p=0.169). In the multivariable analysis, tumor size (per 1 mm) (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03–1.11; p<0.001) and ablative margin (per 1 mm) (HR, 0.81; 95% CI, 0.70–0.92; p=0.002) were significantly associated with local tumor recurrence. Only tumor size (per 1 mm) (odds ratio, 1.08; 95% CI, 1.02–1.15; p=0.015) was significantly associated with complications. Conclusions MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab was 21.1 months (range, 18.8 months-not reached) and 10.5 months (range, 8.2‒12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.3 months-not reached) and 4.0 months (range, 2.5‒6.4 months), respectively. The objective response rates based on response evaluation criteria in solid tumors (RECIST) criteria version 1.1 and modified RECIST were 33.3% and 54.2%, respectively. On multivariate analysis, Child-Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02‒0.76, p = 0.02) and intrahepatic tumor occupancy rate &lt;50% (hazard ratio &lt;0.01, 95% CI 0.003‒0.35, p &lt;0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths and remains a major burden on health-care systems worldwide. The incidence of HCC continues to rise globally, despite preventative efforts being made. Aims: This study aimed to investigate epidemiological changes observed in the aetiology and survival outcomes of HCC patients at Klinikum Klagenfurt am Wörthersee between 2012 and 2023. Methods: This was a retrospective, single-centre cohort observational study. Two time-periods (2012-2017 and 2018-2023) were created to enable comparison between the respective intervals. Results: More patients were diagnosed with HCC during the second time-period, proving that the incidence of HCC is rising or the referral patterns changing. The median age of diagnosis was 72.5 years (SD 8.6). Patients were on average 2 years younger in the second time-period compared to the first (p = 0.042). Alcohol remained the leading underlying aetiology of HCC and no statistically significant change was seen over time (p = 0.353). Nevertheless, a clear upward trend in the number of NASH cases was evident over time (n = 15, n = 28 respectively). Nearly half of the patient population did not have a raised AFP at the time of diagnosis. The survival time for HCC patients remained similar between time-periods, with a median overall survival time of 20.5 months (95% CI 16.8-24.2, p = 0.841), despite improvements in management strategies and the availability of new systemic treatments but more advanced stage HCC was documented in the second period. An increasing number of HCC patients without liver cirrhosis were identified during the second time-period (n = 22, n= 47 respectively, p = 0.005). NASH was the most common underlying aetiology in patients without liver cirrhosis (50%), compared to alcohol use in being the primary cause in cirrhotic patients (p < 0.001). Conclusion: HCC continues to be an important health concern in our society. The number of HCC patients without liver cirrhosis is steadily increasing, with NAFLD/ NASH, due to underlying life-style diseases playing an important aetiological role. Continued efforts should be made to prevent HCC and to screen at-risk population groups. Preventative strategies and screening techniques should be adjusted in light of the changing epidemiological landscape of HCC.

This paper presents the case of a 75-year-old female with an extensive lesion located in the hard palate. Intraoral examination revealed an exophytic white lesion that extended from the entire left maxillary alveolar ridge to the palate beyond the midline. A thorough clinical, radiological, and histopathological examination confirmed the diagnosis of oral verrucous carcinoma.

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare low-grade, neuroendocrine-differentiated, cutaneous adnexal tumour, officially recognized by the World Health Organization (WHO) Skin Tumours Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between the sixth and seventh decade, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-coloured, 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus and Web of Science (WoS), using the following keywords: "Endocrine mucin-producing sweat gland carcinoma" and/or "EMPSGC" and/or "skin" AND "cutaneous neoplasms", and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 248 patients were recorded with the majority, 146 females (58,8%) and 102 males (41,1%). The vast majority of the lesions were in the elides (peri-ocular region) and only a minority of cases involved the cheeks, supra-auricular, retro-auricular and occipital region, with very rare cases in the scalp, to which the present is also added (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC and much remains to be done in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by high resistance to conventional chemotherapy, late diagnosis, and high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and play paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors, dependent on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.

ATC is a rare cancer with a slightly growing incidence and a poor prognosis determined by the delay of treatment, usually revealed by an enlarging goiter with compressive symptoms and, more rarely, by inflammatory and thyrotoxic symptoms, a clinic entity called malignant pseudothyroiditis (MPT) mimicking subacute thyroiditis (SAT). With the advent of COVID-19 pandemic, many cases of COVID-19 related SAT were described with the usual clinical presentation enriched by the COVID-19 symptoms, leading to the emergence of atypic clinical pictures. We present the case of a 60-year-old patient who developed, one month after a COVID 19 acute infection, a clinical presentation of SAT with atypical ultrasound features leading to the diagnosis of MPT; histological atypia was misleading, finally making precise diagnosis was difficult. To our best knowledge, this is the first ever reported case of MPT mimicking COVID-19 SAT. We reviewed thirty five cases published to date and discuss the mechanisms underlying MPT physiopathogenesis and the ultrasound and histological features. We point out the similarities between MPT and SAT and the role of ultrasound at clinical presentation workup. Finally there are two key points to remind: First, to perform neck ultrasound in any painful goiter and, in case of atypia, perform a US guided core-needle biopsy, a complementary CT-scan and quickly refer the patient to an expert center. Second, always think that COVID-19 infection is a recent entity and be aware that it can influence the clinical presentation of any disease.

The influence of preoperative examination of oral squamous cell carcinoma (OSCC) mucosal surrounding by VELscope (Visually Enhanced Lesion Scope) on the radicality of surgical treatment of OSCC was the goal of this study.It is the first analysis of its kind with a total number of 122 patients suffering from OSCC with homogenous distribution of different tumor stages randomized into a study and a control group and enrolled in our study after meeting the inclusion criteria. The preoperative checkup by VELscope accompanied by the marking of the range of a loss of fluorescence in the study group was performed before the surgery. We have developed a unique mucosal tattoo marking technique for this purpose. The pathohistological results after surgical treatment, i.e. the margin status, were then compared. We achieved the pathological free margin (pFM) in 55 patients, the pathological close margin (pCM) in 6 cases and we encountered no case of the pathological positive margin (pPM) in the mucosal layer in the study group. In comparison, the control group results revealed pPM in 7 cases, pCM in 14 cases and pFM in 40 of all cases in the mucosal layer. This study proved that the preoperative autofluorescence evaluation of a tumor mucosal surrounding can enhance the ability to reach the pFM resection.

The epithelial cell adhesion molecule (EpCAM) is a cell surface glycoprotein, which is widely expressed on normal and cancer cells. EpCAM is involved in cell adhesion, proliferation, survival, stemness, and tumorigenesis. Therefore, EpCAM is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti-EpCAM monoclonal antibodies (mAbs) using the Cell-Based Immunization and Screening (CBIS) method. We characterized them using flow cytometry, western blotting, and immunohistochemistry. One of the established recombinant anti-EpCAM mAbs, recEpMab-37 (mouse IgG1, kappa), reacted with EpCAM-overexpressed Chinese hamster ovary-K1 cells (CHO/EpCAM) or a colorectal carcinoma cell line (Caco-2). In contrast, recEpMab-37 did not react with EpCAM-knocked out Caco-2 cells. The KD of recEpMab-37 for CHO/EpCAM and Caco-2 was 2.0 × 10-8 M and 3.2 × 10-8 M, respectively. In western blot analysis, recEpMab-37 detected EpCAM of CHO/EpCAM and Caco-2 cells. Furthermore, recEpMab-37 could stain formalin-fixed paraffin-embedded colorectal carcinoma tissues by immunohistochemistry. Taken together, recEpMab-37, established by CBIS method, is useful for detecting EpCAM in various applications.

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, currently predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

Introduction Image Guided Superficial Radiation Therapy (IGSRT) is a novel technology which combines traditional superficial radiation therapy (SRT) with high resolution dermal ultrasound (HRDUS) to treat non-melanoma skin cancers (NMSC). Since development, IGSRT use has expanded dramatically in outpatient clinics. We review the IGSRT literature and state of the art operating principles in US dermatologic practices. Materials and Methods A literature search of electronic databases (Medline, Pubmed, Cochrane Library, Science Direct) combined with various authors’ published and unpublished documents, procedures and clinical experience with IGSRT were synthesized for this paper. Results Studies have demonstrated IGSRT consistently delivers high cure rates( >99%) with low complications for early stage (stage 0, I, or II) squamous cell and basal cell carcinomas. Control rates are statistically superior to non-image guided SRT and external beam radiation (XRT) as well as Mohs Micrographic Surgery(MMS). This improvement is attributed to in-vivo dermal tumor visualization via HRDUS and using an interdisciplinary approach to deliver care. IGSRT use in the dermatologic clinic for early stage NMSCs has become common practice and continues to expand. Conclusion While the safety and cosmetic benefits of SRT/XRT has been long documented, IGSRT represents a significant leap forward in efficacy (statistically significant) by adding in-vivo dermal tumor imaging. Results rival and appear on one study to surpass tumor control obtained with MMS. A contributing factor to the success may be the availability and use of an interdisciplinary team approach that includes dermatologists, radiation therapists, radiation oncologists and medical physicists. The high tumor control rates, minimal side effects, favorable cosmesis and ability to treat multiple lesions per session using IGSRT is establishing this modality as a standard first line therapy for early stage NMSCs in dermatology clinics. IGSRT may represent the most effective option for the non-surgical treatment of early stage NMSC to date.

Standard Non-Melanoma Skin Cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in case of advanced tumors. Exosomes, integral to carcinogenesis, are found in NMSC, releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived exosomes remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. A systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived exosomes, their molecular cargo and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend exosome mechanisms and explore their potential in cancer diagnosis and treatment.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but sometimes experience difficulty in making the diagnosis. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 41 (98%) of 42 SCLCs and 40 (90%) of 44 LCNECs. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining &gt;10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC.

Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer, comprising a disproportionate share of thyroid cancer-related mortalities despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for MTC patients. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. AI-driven precision oncology can significantly enhance the diagnostic work-up, staging, risk stratification, management, and follow-up care of MTC patients by processing vast amounts of complex data quickly and accurately. AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in MTC management enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being for all at all ages. By leveraging AI and holomics, we can strive towards making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. In conclusion, the integration of holomics and AI in the management of medullary thyroid carcinoma represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of MTC treatment and care.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide and a major global health burden. The treatment of HCC has experienced a paradigm shift in the last few years, following the discovery of immunotherapy. However, despite the profound success of immunotherapy in other cancer types, their response in HCC remains unsatisfactory. Some of the reasons that can explain this poor response include the immunosuppressive microenvironment of HCC, the absence of reliable biomarkers for response, and drug resistance. Previous preclinical and clinical studies have highlighted the role of combination therapy in overcoming some of these hurdles. In this article, we discuss the benefit of combining immune checkpoint inhibitors (ICIs) with stereotactic body radiation therapy (SBRT) in HCC and shed light on promising clinical trials.

Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC=1.00, P=0.001) from healthy controls in plasma EVs and HCC from HCA (AUC=0.950, P=0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA, and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC.

The IMbrave150 trial established atezolizumab with bevacizumab (A+B) as standard care for hepatocellular carcinoma (HCC), recommending an esophagogastroduodenoscopy (EGD) within 6 months of treatment initiation to prevent bleeding from esophagogastric varices. The necessity of mandatory EGD for all patients remains unclear. We retrospectively analyzed 112 HCC patients treated with A+B at five Canadian cancer centers from July 1, 2020, to August 31, 2022. A+B was the first-line therapy for 90% of patients, with median overall survival at 20.3 months and progression-free survival at 9.6 months. There was no survival difference between patients with bleeding and those without. Before A+B, 71%(79) of patients underwent an EGD within 6 months, revealing varices in 41%(32) and requiring intervention in 19%(15). The overall bleeding rate was 15%(17), with GI-specific bleeding occurring in 83%(5) of the EGD group and 17%(1) of the non-EGD group (p=0.24). Non-GI bleeding was observed in 10%(11) of patients. Outcomes for HCC patients treated with A+B in Canada were comparable to IMbrave150. Our study showed twice the rate of varices detection and treatment compared to IMbrave150, reflecting real-world treatment of high-risk populations. There was no increased GI bleeding in patients without pre-treatment EGD, supporting a selective EGD approach.

Papillary thyroid carcinoma (PTC) presents a significant health concern, particularly among Hispanic women in the United States, who exhibit a disproportionately higher chance of developing an advanced disease when compared to the non-Hispanic population. Emerging evidence suggests coagulation factor X, encoded by F10 gene, has a potential role in inhibiting cancer cell migration. However, comprehensive investigations into the differential expression patterns of F10 in Hispanic versus non-Hispanic females remain limited. RNA-sequencing data was acquired from the TCGA database for white female patients, 166 non-Hispanic and 25 Hispanic. A statistically significant (p &lt; 0.05) 2.06-fold increase in F10 expression levels was detected in disease-free tumors compared to recurrent PTC tumors. Furthermore, an increase in F10 gene expression levels was also observed corresponding to approximately a 1.74-fold increase in non-Hispanic patients compared to Hispanic patients. The probability of tumor recurrence was 1.82 times higher in the cohort with low expression of F10 compared to the high expression cohort, correlating with the lower disease-free rates observed in Hispanic patients’ cohort when compared to non-Hispanics. This finding underscores the relevance of ethnic disparities in molecular profiles for understanding cancer susceptibility. Identifying F10 as a potential prognostic biomarker highlights avenues for targeted interventions and contributes to improving diagnostic and treatment strategies for diverse patient populations.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

Objective: Local ablation therapies (radiofrequency ablation (RFA), and microwave ablation (MWA)) are important as curative treatment option in patient with early-stage hepatocellular carcinoma (HCC) and option for intrahepatic tumor volume reduction in those with unresectable HCC. Various techniques; contrast-enhanced ultrasound (CEUS), real-time virtual sonography (RVS), artificial pleural and ascites fluid infusion, and body position change (BPC) have been used to accurately and safely perform local ablation therapies. However, there have been few reports on the usefulness of BPC. Therefore, this study focused on the usefulness of BPC during local ablation therapies in patients with HCC. Methods: We evaluated the technical success rates, treatment time, and prognosis of 283 nodules treated with local ablation therapies. Furthermore, we defined nodules adjacent to large vessels or extrahepatic organs, or poorly visible nodules using US as HCC in high-risk locations. High-risk locations HCC were classified into phase 1 (before active use of BPC, January 2018 to December 2019) and phase 2 (after active use of BPC, January 2020 to January 2022). Results: One hundred seventy-six nodules (62%) were classified as high-risk location group. Compared to non-high risk HCC, treatment-assist techniques, such as BPC (61 vs. 24 %, p<0.001), artificial pleural fluid infusion (24 vs. 5.6%, p<0.001), artificial ascites infusion (50 vs. 11%, p<0.001), fusion imaging (28 vs. 8.4%, p<0.001) and CEUS (26 vs. 4.7%, p<0.001) were performed more frequently for high-risk HCC. The technical success rates were 96% (271/283 nodules), 96% (167/173 nodules) and 95% (102/107 nodules), for all nodules, the high-risk location group and the non-high risk location group, respectively. In the high-risk location group, the technical success rates of the group without BPC were lower than that with BPC (91 vs. 99%, p=0.015). Only BPC was a related factor for the technical success rate for high-risk locations HCC (OR 10 (1.2-86), p=0.034). In contrast, no differences were found in the treatment time, the local tumor progression rates, intrahepatic distant recurrence rates, and overall survival between the group with BPC and that without BPC in the high-risk location HCC. Conclusion: BPC during local ablation therapies in patients with HCC in high-risk locations was safe and efficient. Body position should be adjusted for HCC in high-risk locations to maintain good US visibility and ensure safe puncture route in patients undergoing local ablation therapies.

Hepatocellular carcinoma (HCC) is characterized by uncontrolled cellular proliferation driven by aberrant signal transduction. Cells respond to potential carcinogenic signals by inducing cellular senescence (CS) as a defense mechanism. However, assessing CS levels in various tumors is challenging due to heterogeneity and the lack of universal CS markers. This study integrates single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from HCC samples to analyze gene expression profiles. HCC-specific senescence-related pathways are identified, and genes from these pathways distinguish molecular subtypes associated with senescence in HCC. These subtypes exhibit significant variations in biological and clinical attributes. A specific CS risk model is developed, revealing associations between CS scores and prognosis, clinical staging, immune infiltration, immunotherapy response, and drug sensitivity. The key gene G6PD is identified as a potential senescence-related target in liver cancer. Molecular experiments confirm the effective suppression of HepG2 cell proliferation, invasion, and migration upon G6PD knockdown. In summary, this analysis enhances our understanding of HCC-specific senescence molecular features and introduces a novel senescence-related biomarker, offering promising implications for future research.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by qRT-PCR, and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabil-ities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions on migration characteristics. Sclerostin expres-sion was evaluated in clinical cases by immunohistochemistry at the OSCC jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The re-sults presented are the first data suggesting a possible involvement of sclerostin in the bone inva-sion process of OSCC, which needs to be further investigated

(1) Background: China holds the highest esophageal squamous cell carcinoma (ESCC) incidence areas in the world, with some areas of incidence over 100 per 100,000. Despite extensive public health efforts, its etiology is still poorly understood. This study aims to review and summarize past research into potential etiologic factors for ESCC in China. (2) Methods: Relevant observational and intervention studies were systematically extracted from four databases using key terms, reviewed using Rayyan software, and summarized into Excel tables. (3) Results: Among the 207 studies included in this review, 130 studies were focused on genetic etiologic factors, followed by 22 studies focused on dietary-related factors, 18 studies focused on HPV-related factors, and 37 studies focused on other factors. (4) Conclusions: ESCC in China involves a variety of factors including genetic variations, gene-environment interactions, dietary factors like alcohol, tobacco use, pickled vegetables, and salted meat, dietary behavior such as hot food/drink consumption, infections like HPV, poor oral health, gastric atrophy, and socioeconomic factors. Public health measures should prioritize genetic screening for relevant polymorphisms, conduct comprehensive investigations into environmental, dietary, and HPV influences, enhance oral health education, and consider socioeconomic factors overall as integral strategies to reduce ESCC in high-risk areas of China.

This study aims to explore the utilization of deep learning models, specifically the innovative Multi-Modal Contextual Fusion Convolutional Neural Network (MSHA), for the detection and diagnosis of Adrenocortical Carcinoma (ACC) using computed tomography (CT) images. The objective is to develop an accurate and reliable model that can assist in the effective detection and classification of ACC. The study utilizes a dataset comprising contrast-enhanced CT images from 53 confirmed ACC patients. The MSHA model is employed, which incorporates a combination of mixed-scale dense convolution, self-attention mechanism, hierarchical feature fusion, and attention-based contextual information techniques. Evaluation metrics are used to assess the performance of the MSHA model, and a comparison is made with other established models, including ResNet50, VGG16, VGG19, and InceptionV3. The evaluation of the MSHA model demonstrates high performance, with an accuracy of 96.65% and precision, sensitivity, specificity, and F1 score of 96.0%. These results highlight the MSHA model's capability in accurately detecting and classifying ACC. Furthermore, compared to other models, the MSHA model outperforms ResNet50, VGG16, VGG19, and InceptionV3, indicating its superior performance in ACC detection and diagnosis. The findings of this study suggest that the MSHA model holds significant potential in assisting healthcare professionals with the detection and diagnosis of ACC. With its advanced features and contextual fusion techniques, the MSHA model achieves high accuracy and performance. The results highlight the clinical significance of this novel model and its potential to improve patient management and outcomes in the detection and diagnosis of ACC using CT images.

Despite recent advancements, therapies remain ineffective against advanced oral squamous cell carcinoma (OSCC), resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Yet, the exact mechanisms driving CAP-induced cancer cell death are not fully understood. This study revealed a significant reduction in the viability of OSCC cell lines, inactivation of AKT and ERK, and the downregulation of the miR-21, miR-31, miR-134, miR-146a and miR-211 expression followed the CAP treatment. Pretreatment with ZVAD, 3-MA, and Fer-1 synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways by CAP. Activation of AKT and ERK, alongside combined treatments using death inhibitors and miRNA mimics, counteracted the cell mortality associated with CAP. CAP-induced downregulation of miR-21, miR-31, miR-187 and miR-211 expression was rescued by AKT and ERK activation. Additionally, CAP treatments notably inhibited the growth of SAS cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study indicates that CAP jet treatment diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TNM-stages. Locoregional control rates have been impressive even from the 2D-radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there had been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally-advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT.

Liver is the sixth most common site of primary malignant tumors, and the third leading cause of cancer death worldwide. Hepatocellular carcinoma is the most common primary liver malignancy and lungs, abdominal lymph nodes and adrenal glands are the most common sites of its metastasis. We present a rare case of an isolated metastasis of a hepatocellular carcinoma in the left mandibular ramus, with regards to its clinical and radiological presentation and with regards to possible routes of the metastatic spread.

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer, thus it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome's role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy.

Hepatocellular Carcinoma (HCC) continues to pose a substantial global health challenge due to its high incidence and limited therapeutic options. In recent years, the Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has emerged as a critical signaling cascade in HCC pathogenesis. The review commences with an overview of the JAK/STAT pathway, delving into the dynamic interplay between the JAK/STAT pathway and its numerous upstream activators, such as cytokines and growth factors enriched in pathogenic livers afflicted with chronic inflammation and cirrhosis. This paper also elucidates how the persistent activation of JAK/STAT signaling leads to diverse oncogenic processes during hepatocarcinogenesis, including uncontrolled cell proliferation, evasion of apoptosis, and immune escape. In the context of therapeutic implications, this review summarizes recent advancements in targeting the JAK/STAT pathway for HCC treatment. Preclinical and clinical studies investigating inhibitors and modulators of JAK/STAT signaling are discussed, highlighting their potential in suppressing the deadly disease. The insights presented herein underscore the necessity for continued research into targeting the JAK/STAT signaling pathway as a promising avenue for HCC therapy.

Keywords: Y RNA; Canine hepatocellular carcinoma, canine hepatocellular adenoma

This study aimed to evaluate the diagnostic and prognostic roles of GATA3 immunohistochemistry in urothelial carcinoma (UC) through a meta-analysis. We investigated GATA3 immunohistochemical expression rates and performed a subgroup analysis based on tumor site, study location, and histological subtypes. The overall survival rates of patients with GATA3-positive and negative UC were compared. The estimated GATA3 expression rate was 0.748 (95% confidence interval [CI]: 0.704–0.787). GATA3 expression rates in the urinary bladder and urinary tract were 0.775 (95% CI: 0.727–0.818) and 0.614 (95% CI: 0.426–0.774), respectively. The GATA expression rates of noninvasive and invasive UCs were 0.965 (95% CI: 0.938–0.980) and 0.644 (95% CI: 0.581–0.702), respectively. In invasive UCs, there was a significant difference in GATA3 expression between non-muscular invasion and muscular invasion subgroups (0.937, 95% CI: 0.883–0.967 vs. 0.753, 95% CI: 0.645–0.836). GATA3 expression was the highest in the microcytic subtype among the histologic subtypes (0.952, 95% CI: 0.724–0.993). There was a significant correlation between GATA3 expression and better prognosis (hazard ratio: 0.402, 95% CI: 0.311–0.521). Taken together, GATA3 expression significantly correlated with low-stage and better prognosis in UC. GATA3 expression is highly variable across histological subtypes and it is careful interpreting GATA3 expression.

The burden of hepatocellular carcinoma (HCC) continues to pose a significant global health problem. Several systemic therapies have recently been shown to improve survival for patients with unresectable disease. However, evidence is limited to support the use of neoadjuvant or adjuvant systemic therapies in patients with resectable disease, despite the high risk of recurrence. Neoadjuvant and adjuvant systemic therapies are being investigated for their potential to reduce recurrence after resection and improve overall survival. Our review identified various early-phase clinical trials showing impressive preliminary signals of pathologic complete response in resectable disease and others suggesting neoadjuvant therapies, particularly when combined with adjuvant strategies, may convert unresectable disease to resectable and cause significant tumor necrosis, potentially decreasing recurrence rates. The role of adjuvant therapies alone may also have a role in the management of these patients, particularly in reducing recurrence rates. Heterogeneity in trial design, therapies used, patient selection, and a scarcity of randomized phase III trials necessitate the cautious implementation of these treatment strategies. Future research is required to identify predictive biomarkers, optimize the timing and type of therapeutic combinations, and minimize treatment-related adverse effects, thereby personalizing and enhancing treatment strategies for patients with resectable and borderline resectable HCC.

No abstract available

A wide variety of renal neoplasms can have cystic areas. It happens for different reasons: some tumors have an intrinsic cystic architecture, others have a pseudocystic degeneration of necrotic foci or they have cystically dilated renal tubules constrained by stromal neoplastic cells. Clear cell renal cell carcinoma (CCRCC), either solid or cystic, is the most frequent type of renal cancer. While pseudocysts are found in high-grade aggressive CCRCC, cystic growth is associated to low-grade indolent cases. The latter also form through a cyst-dependent molecular pathway and they are more frequent in patients suffering from VHL disease. The differential diagnosis with multilocular cystic renal neoplasm of low malignant potential and clear cell papillary renal cell tumor can be especially hard and it requires a focused macroscopical and microscopical pathological analysis. As every class of renal tumors include cystic forms, a knowledge of criteria for a differential diagnosis is mandatory.

We present a case of neglected atypical high grade prostatic stromal sarcoma (PSS) at the transitional zone , invading the peripheral zone, prostatic capsule & peri prostatic fat reaching to pelvic side wall, it showed T2WI hyperintense signal (compared to typical cases of PSS showing T2WI hypointense signal) corresponding to developing on top of pre-existing nodular hyperplasia. Careful reviewing of prostatic central / transitional zone lesions is mandatory especially at T2WI, diffusion & contrast images to exclude malignancy which can be easily missed due to multiple signal patterns described. Most common tumors at transitional zone is stromal sarcoma which could be typical showing T2 hypointense signal or atypical showing T2 hyperintense signal intensity.

Recently, a database of human piRNAs has been created, which allows studying the binding of many piRNAs to mRNAs of genes involved in many diseases, including cancer. In the present work, we investigated what piRNAs can interact with candidate esophageal squamous cell carcinoma (ESCC) genes. The binding of 480 thousand piRNAs with mRNAs of 66 candidate ESCC genes was studied. Bioinformatic studies found that piRNAs bind only to the mRNAs of nine candidate genes: AURKA, BMP7, GCOM1, ERCC1, MTHFR, SASH1, SIX4, SULT1A1, and TP53. It has been shown that piRNAs can bind to mRNA by overlapping nucleotide sequences in limited 3'UTR and 5'UTR regions called clusters of binding sites (BSs). The existence of clusters of piRNA BSs significantly reduces the proportion of nucleotide sequences of these sites in the mRNA of target genes. Competition between piRNAs occurs for binding to the mRNA of target genes. Individual piRNAs and groups of piRNAs that have separate BSs and clusters of BSs in the mRNAs of two or more candidate genes have been identified in the mRNAs of these genes. This organization of piRNAs BSs indicates the interdependence of the expression of candidate genes through piRNAs. Significant differences in the ability of genes to interact with piRNAs avoid the side effects of piRNAs on genes with the lack of binding of such piRNAs. Individual piRNAs and sets of piRNAs are proposed and recommended for the diagnosis and therapy of ESCC.

Renal Cell Carcinoma (RCC) is generally represented by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT to correctly identify RCC lung metastases using histology as standard of truth. Records of 350 patients affected by RCC and with CT evidence of at least one lung nodule, were retrospectively analyzed. Inclusion criteria were: a) histologically proven RCC; b) [18F]FDG-PET/CT performed prior to lung surgery; c) lung surgery with histological analysis of surgical specimens; d) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven (n=67) patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57/107 of cases, while 50/107 lesions were related to others lung malignancies. Applying a cut-off of SUVmax ≥2, the sensitivity and the specificity of [18F]FDG-PET/CT for detect RCC lung metastases were 33.3% (95% CI: 21.4% - 47.1%) and 26% (95%CI: 14.6% - 40.3%), respectively. The analysis demonstrated sub-optimal diagnostic accuracy of [18F]FDG-PET/CT to discriminate between RCC lung metastases versus other malignancies. However, semiquantitative analysis including also volumetric parameters (MTV and TLG) can support [18F]FDG-PET/CT image interpretation.

Penile squamous cell carcinoma (SCC) is a rare disease. Treatment options for advanced penile cancer are often limited and prognosis remains poor. We reported a 52-year-old male recurrent and metastatic penile SCC patient with high PD-L1 expression(90%) and TMB(14.4 muts/Mb). He had undergone penectomy, bilateral inguinal lymph node dissection and excision of the abdominal wall mass during two surgeries. Despite cisplatin-based concurrent chemoradiotherapy and sequential chemotherapy with docetaxel plus cisplatin were then carried out, the carcinoma still had progressed. The patient then obtained progression free survival exceeding 32 months with continuous sintilimab, although new onset of ICI-induced diabetes after 24 cycles of sintilimab and required sustained insulin treatment. He didn’t have positive type 1 diabetes associated autoantibodies, but had susceptible HLA genotype DR3-DQ2 haplotype. This is the first patient with radiation and multichemorefractory penile SCC obtained remarkable anti-tumor effect of partial regression exceeding 32 months during continuous sintilimab.

The prevalence of obesity or metabolic syndrome is increasing worldwide (“Globally metabodemic”). Approximately 25% of adult general population is suffering from nonalcoholic fatty liver disease (NAFLD) which has become serious health problem. Hepatic fibrosis is the most significant determinant of all cause and liver -related mortality in NAFLD. Noninvasive test (NIT) should be urgently required to evaluate hepatic fibrosis in NAFLD. Fibrosis-4 (FIB-4) index is the 1st triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness especially for general physicians or endocrinologists, although FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the 2nd step after triaging by FIB-4 index. The leading cause of mortality in NAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. NAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation (SLKT). FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocullar carcinoma (HCC) but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, FIB- 4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of FIB-4 index as 1st step NIT in management of NAFLD.

Beginning with the discovery of the BRCA ovarian cancer susceptibility genes and subsequent detailed examination of risk reduction salpingo-oophorectomy (RRSO) specimens, a new paradigm of ovarian carcinogenesis has unfolded with attention to the distal fallopian tube. The primary focus has been an early cancer in the fallopian tube which is seen in virtually all incidentally discovered high-grade serous cancers in asymptomatic women. This high-frequency of tubal involvement in early serous cancer - serous tubal intraepithelial carcinoma or STIC - has galvanized attention to this organ as a primary source of this disease. However, an enduring mystery has been the relatively low frequency of STIC in fallopian tubes of women with advanced malignancy. This paradox, a high-frequency of tubal involvement early and a low-frequency late in the disease process has spurred interest in other potential sources, such as the ovarian surface or secondary Mullerian system. However, because essentially all high-grade serous carcinomas are linked by TP53 mutations, and because fallopian tubes frequently contain early serous proliferations (ESPs) with these mutations, attention has turned to the possibility that nonmalignant but TP53 mutated tubal epithelium could be responsible for an eventual malignancy. Recent data have shown evidence of lineage continuity between ESPs and concurrent serous carcinomas prompting the concept of "precursor escape". This creates a 2nd component of the paradigm by which cells from early lesions can escape the fallopian tube and undergo future malignant transformation later, emerging suddenly as widespread malignancy. This dualistic model thus explains the paradox and opens new questions pertaining to the challenge of both early detection and prevention of this lethal malignancy.

Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in chemical, but not bacterial, constituents of these products. In this study, we explore the composition and function of the bacteriome in ST products from 4 countries using q-PCR and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4E+6) and highest in Yemeni shammah (6.6E+11). A total of 491 species-level taxa, many of which are potentially novel, belonging to 178 genera and 11 phyla were identified. Species richness and diversity were highest for Swedish snus and lowest for Yemeni shammah. Bacillus, Paenibacillus, and Oceanobacillus spp. were the most abundant in American snuff; species of Pseudomonas, Massilia, Propionibacterium, Puniceispirillum and Gloeothece predominated in Swedish snus. In Sudanese toombak, Facklamia, Desemzia, Atopostipes and Lysinibacillus spp. accounted for the majority of the bacteriome. Yemeni shammah exclusively contained Bacillus spp. PICRUSt functional prediction showed that genes encoding cadmium/zinc and nickel transport systems were enriched in the presumptively “high carcinogenicity” products. The bacteriome of ST products thus differed qualitatively, quantitatively and functionally. The relevance of these differences, particularly with respect to nickel and cadmium, to oral carcinogenesis warrants further investigation.

Epidermal Growth Factor Receptor (EGFR) expression is an important aspect in the non-small cell lung cancer (NSCLC) diagnosis and treatment. Therefore, it becomes important to identify factors that may influence EGFR level. There are reports suggesting that one of the positive EGFR gene transcription regulators may be Special AT-rich Binding Protein 1 (SATB1), but so far these ob-servations have not been confirmed in NSCLC. The main aim of the present study was to investigate the possible links between the EGFR and SATB1 expression on both protein and mRNA levels in NSCLC clinical samples, and to correlate the obtained results with the clinical-pathological data of the patients. Additionally, we analysed the relationships between the expression levels of EGFR and the known tumour promoters, in-cluding Ki67 proliferative antigen and EMT-promoting transcription factors - SLUG, SNAIL, and Twist1. We demonstrated that EGFR expression in NSCLC was positively correlated both with the SATB1 level and with the expression of EMT-promoting proteins. Moreover, we were the first to analyse EGFR expression exclusively in NSCLC cancer cells without the interference caused by respiratory epithelium and tumour stroma. Our analysis revealed that the prognostic significance of EGFR expression was dependent on tumour histology and differed significantly between the AC and LSCC samples.

Background/Objectives: Basal cell carcinoma (BCC), the most prevalent form of human cancer, is traditionally treated by surgical and alternative destructive or topical chemical means, each with its advantages, challenges and drawbacks. We describe our experience treating BCCs with a topical concentrate of proteolytic enzymes enriched in bromelain (CPEEB) sourced from pineapple stems. CPEEB has strong proteolytic, antitumor-proapoptotic and inflammation modulation activities, and is approved for debridement of deep burns and starting phase 3 for chronic wounds. Methods: In the first proof of concept (POC) study (published), six BCCs on 3 individuals were treated with 5-6 daily CPEEB 10% topical applications under a Zinc Oxide based occlusive dressing for 9-12 hours each during a period of up to 10 days. These patients were followed for up to 4 years. In an additional 2 POC studies, 16 patients with one BCC each were treated every other day for a total of 7 applications of topical CPEEB 5% under a variety of occlusive dressings. The wounds were followed for up to 2 months before undergoing diagnostic excisional biopsy. Results: In the first study, clinical assessment of the BCCs and 2 excisional biopsies after 6 months suggested that all lesions were eradicated with spontaneous healing within ~2 weeks without clinical or histological recurrence for over 4 years. In the 2 subsequent studies, 16 histologically diagnosed superficial and nodular BCCs were treated using 4 application techniques. Excisional histology after 2 months confirmed BCC eradication in 7 of the patients. In 9 patients, with compromised occlusive dressings, histological eradication was incomplete. Treatment was well tolerated by all patients with the expected local skin reactions that completely healed within 2-3 weeks. Conclusions: Topical CPEEB 10% and 5% resulted complete eradication of the BCC when appropriately applied. CPEEB was well tolerated in all patients and all treated sites’ erosions healed without scars in <3 weeks. Further research is necessary to corroborate the results, refine the application technique and complete the regulatory process.

Introduction: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTC), papillary thyroid carcinoma (PTC) is the most common. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis, in order to obtain a personalized and more effective treatment of patients. Aims: This study aims to evaluated 1) miRNAs expression in a series of DTC, and the association with the presence of selected genetic mutations, in order to improve diagnosis and predict biologic behavior of DTC/PTC. 2) the reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. Material and methods: This series includes 176 samples (98 cytology samples and 78 formalin-fixed paraffin embedded (FFPE) tissues) obtained from 106 patients submitted to surgery, being 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and the results were analyzed using the 2- ΔΔCT method, using miR16 as an endogenous control. The discriminative ability of miRNAs expression regarding PTC diagnosis was evaluated using the area under the Receiver Operating Characteristic Curve (AUC). The association of miRNAs expression, clinicopatological features and genetic alterations (BRAF, RAS and TERTp) was evaluated in PTCs. Results/Discussion: All the analyzed miRNAs showed a tendency to be over expressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant than in benign tumors. In histology, corresponding discriminative abilities regarding PTC diagnosis were: miR-146b (AUC0.94, 95%CI 0.87-1), miR-221 (AUC0.79, 95%CI 0.68-0.9), miR-222 (AUC0.76, 95%CI 0.63-0.89) and miR-15a (AUC0.85, 95%CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); mi-R221 se=68.4, sp=90; miR222 se=73, sp=70, and mi-R15a se=72, sp=80. MicroRNAs were associated with aggressive clinicopathological features and tumor progression in PTCs (p &lt; 0.05), particularly for miR-222. Our data reveals a significant association between higher expression levels of miR-146b, miR-221 and miR-222, with the presence of BRAF mutation (p&lt;0.001), and miR-146b (p=0.016) and miR-221 (p=0.010) with the presence of RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Although this study has a relatively small sample size, over expression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs showed a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations results could be useful for an accurate diagnosis of DTCs/PTCs in FNAC.

(1) Background: Considering highly selected patients with ductal carcinoma in situ (DCIS), active surveillance is a valid alternative to surgery. Our study is aimed at showing the reliability of post-biopsy complete lesion removal, documented by mammogram, as additional criterion to select these patients. (2) Methods: 2173 Vacuum Assisted Breast Biopsies (VABB) documented as DCIS have been reviewed. Surgery has been performed in all cases. We retrospectively collected the reports of post-VABB complete lesion removal and the histological results of the biopsy and surgery. We calculated the rate of upgrade of DCIS identified on VABB upon excision for patients with post-biopsy complete lesion removal and for those showing residual lesion. (3) Results: We observed 2173 cases of DCIS: 408 classified as low grade; 1262 as intermediate grade; 503 as high grade. The overall upgrading rate to invasive carcinoma was 15.2% (330/2173). The upgrade rate was significantly lower (8.2%) when considering patients showing mammographically documented complete removal of the lesion. (4) Conclusion: The absence of mammographically documented residual lesion following VABB is associated to a lower upgrading rate of DCIS to invasive carcinoma on surgical excision and should be considered when deciding the proper management DCIS diagnosis.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

Background: Ovarian clear cell carcinoma (OCCC) is a type of ovarian cancer with a poor prognosis if detected in the progressive stage since there is less effective chemotherapy. Recent advancements in molecular-targeted drugs have not substantially affected OCCC treatment. Therefore, we explored the potential of targeting MDM2 in OCCC cells. Methods: We used TOV-21G and KOC7c cells as the ARID1A mutant-type, and RMG-I and ES2 cells as the ARID1A wild-type. Then, we performed small interfering library screening, Western blotting, real-time polymerase chain reaction analysis, cell proliferation assay, cell cycle analysis, time-lapse cell proliferation assessment, and DNA damage assessment. Next, to generate murine intraperitoneal tumors, 7.5 × 106 TOV-21G cells in 200 μL of phosphate-buffered saline were injected subcutaneously into the intraperitoneum in 5–6-week-old athymic nude mice. Results: Using various cell lines with ARID1A mutations or without mutation, the results showed that the interference of MDM2 effectively reduced cell proliferation in ARID1A-mutant cells but not in ARID1A wild-type cells. Additionally, interference with ARID1A against ARID1A wild strains reproduced susceptibility to MDM2 interference. In vivo experiments demonstrated that nutlin-3, an MDM2 inhibitor, significantly suppressed tumor growth in the ovarian cancer mouse model. Conclusion: These findings suggest that targeting MDM2 may be a viable strategy for the treat-ment of ARID1A-mutated OCCC, offering a new therapeutic approach for this challenging type of cancer.

Background. Sarcopenia is characterized by progressive loss of muscle mass and function. It is often associated with frailty, a syndrome linked to physical disability and shortened survival in various diseases, including cancer patients. Low serum alanine aminotransferase (ALT) values, representing low muscle mass (sarcopenia), is a routine blood test that was shown to be associated with increased frailty and subsequently shortened survival in several cancers. In the current study, we aimed to test the association between low ALT and shorter survival in renal cell carcinoma (RCC) patients and survivors. Methods. This was a retrospective analysis of RCC patients and survivors, both in and out-patients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. Results. We identified records of 3,012 patients diagnosed with RCC. The final cohort included 1,830 eligible patients (mean age 65.6 ± 13.3 years, 68% were men) of whom only 179 underwent surgical treatment. Out of the eligible cohort, 811 patients (44.3% ( had ALT < 17 IU/L. The mean ALT value of patients within the low ALT group was 11.79 IU/L while the mean value in the higher ALT level group was 24.44 IU/L (p < 0.001). Patients in the lower ALT group were older (67.9 vs. 63.7 years; p < 0.001) and had lower BMI (26.6 vs. 28; p < 0.001). In addition, patients with low ALT had lower hemoglobin values (12.14 vs. 12.91 g/dL; p < 0.001), higher serum creatinine (1.49 vs. 1.14; p < 0.001) and higher platelets to lymphocytes ratio (178 vs. 156; p < 0.001). In a univariate analysis, low ALT levels were associated with a 72% increase in mortality (95% CI 1.46-2.02, P < 0.001). In a multivariate model controlled for age, male gender, hemoglobin, platelets, LDH, neutrophil to lymphocytes ratio and platelets to lymphocytes ratio, low ALT levels were associated with a 27% increase in mortality (HR = 1.27, 95% CI 1.08 – 1.51; p = 0.005]. Conclusion. Low ALT values, indicative of sarcopenia and frailty, are associated with shortened survival of RCC patients and survivors and could potentially be applied for optimizing individual treatment decisions.

Biosensors have emerged as a promising tool for early detection of oral squamous cell carcinoma (OSCC) due to their rapid, sensitive, and specific detection of cancer biomarkers. Saliva is a non-invasive and easy-to-obtain biofluid that contains various biomarkers of OSCC, including carcinoembryonic antigen (CEA). In this study, an electrochemical biosensor for the detection of CEA in Saliva has been developed towards the diagnosis and early screening of OSCC. This biosensor utilized CEA-sensitive aptamer as sensitive elements. Fluorine-doped Tin Oxide (FTO) chip with surface modification of zinc oxide nanorod was employed as transducer. Electrochemical measurements were carried out to detect the responsive signals originated from the specific binding between aptamers and CEAs. The measurement results indicated that this biosensor was responsive to different concentrations of CEA ranging from 1 ng/mL to 80 ng/mL in a linear relationship. The limit of detection (LOD) was 0.75 ng/mL. This biosensor also showed very good specificity and regenerative capability. Stability testing over a 12-day period showed excellent performance of this biosensor. All the results demonstrated that this biosensor have great potential to be used for the detection of CEA in the saliva of OSCC patients. This biosensor provides a promising method for the rapid detection of CEA with convenience, which have great potential to be used as a new method for clinical diagnosis and early screening of OSCC.

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to investigate the comparison among pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were perfomred to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). Results: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 x 109/ L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, an higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS ( p = 0.034) and OS ( p= 0.048). Conclusions: Our study suggests that PIV and SII are two very similar markers that may serve as an independent and significant predictor of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.

Over the few decades, cancer-associated mortalities and morbidities were continuously increased worldwide despite sophisticated technological advancements. Pharmaceutical interventions associated with drugs exhibit a high degree of side effects and toxicities in addition to very high costs. Subsequently, to reduce or to vanish the side effects and high costs, researchers are now exploring natural bioactive compounds such as quercetin in its nanoformulations along with biologics as cargo delivery vehicles. Quercetin along with mesenchymal stromal lineage-derived extracellular vesicles (EVs) possesses an anti-cancer potential that can be explored to treat hepatocellular carcinoma (HCC). Exerting enhanced effect, nano quercetin synergistically with EVs triggers the anti-cancer mechanisms by regulating and dysregulating several signalling mechanisms including NF-κB, p53, JAK/STAT, MAPK, Wnt/β-catenin and PI3K/AKT, in addition to PBX3/ERK1/2/CDK2, and miRNAs modulation. In addition, findings regarding the potential checkpoints of anti-cancer signalling pathways were investigated that offer opportunities to develop engineered EVs incorporated with nano quercetin for the development of novel therapeutics to treat HCC in future. In this present mechanistic review, we abridged the regulation of such signalling mechanisms synergetic approach of nano quercetin and EVs. The regulatory role of EVs in the manifestation of innumerable miRNAs has also been tailed with special context to HCC.