REVIEW | doi:10.20944/preprints201902.0220.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Acute pancreatitis; Etiology; Biliary pancreatitis; Systematic review; Meta-analysis
Online: 25 February 2019 (08:58:59 CET)
Introduction: Cholelithiasis and consumption of alcohol are the most frequent causes of acute pancreatitis (AP), accounting for about 30 to 40% of the cases, respectively. The frequency of acute biliary pancreatitis is high in a certain population in Brazil. Objective: To estimate the global frequencies of acute biliary pancreatitis (ABP), acute alcoholic pancreatitis (AAP) and the cases considered as acute idiopathic pancreatitis (AIP) in studies published from October 2006 to December 31, 2018. Methods: A systematic review of observational studies was performed from October 2006 to December 31, 2018. A meta-analysis by the random effects model was used to calculate the frequencies of global ABP, AIP and AAP and subgroups. Results: Forty-six studies representing 2,341,007 AP cases were included in 36 countries. The overall estimate for acute biliary pancreatitis (ABP) was 41.6% (95% CI 39.2-44.1), followed by acute alcoholic pancreatitis (AAP) with 20.5% (95% CI) 16.6- 24.6) and acute idiopathic pancreatitis (AIP) in 18.3% (95% CI 15.1-27.7). Conclusion: ABP is the most prevalent etiology of AP, being two times more frequent than second-placed pancreatitis. Latin America has a frequency for ABP much higher than the rest of the world. The importance of the etiologic diagnosis is the treatment of the cause for prevention of recurrence.
ARTICLE | doi:10.20944/preprints202106.0579.v1
Subject: Life Sciences, Biochemistry Keywords: intrahepatic, biliary duct; micropatterning, cholangiocyte,; self-organogenesis
Online: 23 June 2021 (12:05:08 CEST)
Background & Aims: Globally, liver diseases account for 2 million deaths per year. For those with advanced liver disease the only curative approach is liver transplantation. However, less than 10% of those in need get a liver transplant due to limited organ availability. To circumvent this challenge, there has been a great focus in generating a bioengineered liver. Despite its essential role in liver functions, a functional biliary system has not yet been developed. In this framework, exploration of epithelial cell self-organogenesis and microengineering-driven geometrical cell confinement allow to envision the bioengineering of a functional biomimetic intrahepatic biliary tract. Approach: Three-dimensional (3D) bile ducts were built in vitro by restricting cell adhesion to two-dimensional (2D) patterns to guide cell self-organization. Tree shapes mimicking the configuration of the human biliary system were micropatterned on glass slides, restricting cell attachment to these areas. Different tree geometries and culture conditions were explored to stimulate self-organogenesis of normal rat cholangiocytes (NRCs) used as a biliary cell model, either alone or in coculture with human umbilical endothelial cells (HUVECs). Results: Pre-seeding the micropatterns with HUVECs promoted luminogenesis with higher efficiency to yield functional branched biliary tubes. Lumen formation, apico-basal polarity, and preservation of the cholangiocyte phenotype were confirmed. Moreover, intact and functional biliary structures were detached from the micropatterns for further manipulation. Conclusion: This study presents physiologically relevant 3D biliary duct networks built in vitro from 2D micropatterns. This opens opportunities for investigating bile duct organogenesis, physiopathology, and drug testing.
ARTICLE | doi:10.20944/preprints202209.0441.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: biliary atresia; complications; clavien-dindo classification; comprehensive complication index; cci
Online: 28 September 2022 (12:19:37 CEST)
Introduction Kasai procedure in children with biliary atresia (BA) is associated with several complications in the short-term. The Comprehensive Complication Index (CCI) is a validated metric in adult surgery for the analysis of complication and morbidity in surgical patients. We aimed to analyze the CCI for the first time in BA infants and to corelate its association with the outcome. Material and Methods Retrospective review of medical records of infants with type III BA undergoing Kasai procedure between January 2011 and December 2021 at our institution. All unexpected events were ranked according to the Clavien-Dindo classification and the CCI per patient was subsequently calculated. Clavien-Dindo grades, individual events, the CCI and the total event number per patient were correlated with the one- and two-year outcome post Kasai. Results 131 events were identified in 101 patients (range 0 – 11 per patient). Forty-four Grade I (33.6%), 67 Grade II (51.1%), 18 Grade III (13.7%) and two sentinel events [> Grade IV] (1.5%) were documented according to Clavien-Dindo, including one death in a cardiac-associated BA patient. None of the complications correlated significantly with a poor outcome. Sixty-three (62.4%) CCI were calculated (range 0 – 100). The mean CCI during the in-patient treatment post Kasai, was significantly higher in patients with a poorer outcome compared to patients with native liver survival at one- and two-year follow-up (22.7 21.7 vs 13.2 18.1; p=0.02). Conclusion Not the severity of complications, but the accumulation of numerous events related to Kasai procedure are associated with a poorer outcome. Therefore, the CCI is an excellent instrument for the postoperative morbidity assessment of BA patients.
CASE REPORT | doi:10.20944/preprints201911.0200.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: BRCA1; BRCA2; biliary tract cancers; ereditary BRCA cancer; somatic mutations
Online: 17 November 2019 (10:44:44 CET)
BRCA-associated hereditary breast and ovarian cancer syndrome (HBOC) implies increased absolute risk also for other malignancies such as cholangiocarcinoma (CCA). However, even if somatic mutations in CCA have been reported, there are no data on its utilization as predisposing genetic factor in a family. For the first time, we utilized CCA somatic BRCA mutation to individualize a family with HBOC. A 47-year-old woman (daughter of a patient died for CCA) accessed to our Genetic Councelling to evaluate her personal cancer risk. We performed a somatic BRCA1/2 NGS analysis on DNA extracted from formalin-fixed, paraffin-embedded CCA-tissue of her mother. After demonstration of pathogenic variant c.6468_6469delTC in BRCA2 gene mutation, the same germline pathogenic variant was found in DNA blood of one of two daugthers. So far, CCA tissue can be utilized, in addition to patient’s selection to specific therapeutic strategies, also to individualize families belonging to HBOC syndrome.
CASE REPORT | doi:10.20944/preprints202008.0217.v1
Subject: Keywords: Castleman disease; radiofrequency ablation; cholangioscopy; SpyGlass DS; biliary tract; obstructive jaundice
Online: 9 August 2020 (15:19:22 CEST)
Castleman disease (CD) rarely presents with obstructive jaundice, which poses a diagnostic and therapeutic challenge to the management of the disease. A 40-year-old man was referred to our hospital for emergent management of upper abdominal pain. An abdominal mass was removed, and the postoperative pathology showed retroperitoneum CD, which was subsequently managed by adjuvant therapy of combination chemotherapy and steroids. One month later, a biliary metal stent was placed due to the presentation of obstructive jaundice. After approximately 3 months, the patient experienced another episode of obstructive jaundice, and SpyGlass DS cholangioscopy (Boston Scientific, Natick, Mass, USA) was performed via the biliary track for biopsy, which pathologically showed biliary malignancies. Radiofrequency ablation was performed with a probe (EMcision, Montreal, Canada), and another uncovered metal stent was placed within the existing metal stent. No stent occlusion occurred during a 6-month follow-up period. In conclusion, CD rarely presents with obstructive jaundice, and a combination of radiofrequency ablation with metal stent implantation under cholangioscopy can prolong the stent patency time and the survival time of patients.
REVIEW | doi:10.20944/preprints202108.0378.v1
Subject: Medicine & Pharmacology, Other Keywords: perihilar cholangicarcinoma; advance perihilar cholangiocarcinoma, perihilar cholangiocarci-noma vascular involvement; biliary cancer.
Online: 18 August 2021 (13:22:01 CEST)
Abstract: Perihilar cholangiocarcinoma (phCC) is the most common type of cholangiocarcinoma, accounting for approximately 60 % of cases, followed by the distal and then the intrahepatic forms. There is not a staging system that allows comparation of all series and extract some conclusions to increase the long-survival rate in this dismal disease. The extension of the resection, which theoretically dependes on the type of phCC, is not closed subject. As surgery is the only known way to achieve a cure, many aggressive approachs have been adopted. Despite extended liver resections and even vascular resections, margins are positive in around one third of patients. In the past two decades, with advances in diagnostic and surgical techniques, the surgical outcomes and survival rates have gradually improved, although variability is the rule, with morbidity and mortality rates ranging from 14% to 76% and from 0% to 19%, respectively. Extended hepatectomies and portal vein resection even right hepatic artery reconstruction for the left side tumors are frequently needed. Salvage procedures when arterial reconstruction is not feasible, as well as hepatopancreatoduodenectomy, are still under evaluation too. In this article, we discuss the aggressive surgical approach to phCC focused on vascular resection. Disparate results on the surgical treatment of phCC made it impossible to reach clear-cut conclusions.
ARTICLE | doi:10.20944/preprints202008.0180.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: biliary atresia; Kasai portoenterostomy; cholangitis; portal hypertension; bile ducts dilatations; native liver survival
Online: 7 August 2020 (09:27:14 CEST)
The prospective study enrolled 144 patients after surgical treatment of biliary atresia in early infancy. We analyze the immediate effectiveness of the surgery and the age-related structure of complications in the up to 16-year follow-up. The immediate 2-year survival rate after the surgery constituted 49.5%. At the time of this writing, 17 of the patients have celebrated their 10th birthdays with good quality of life and no indications for LT. The obtained results underscore the critical importance of surgical correction of BA by Kasai surgery during the first 60 days of life and subsequent dynamic follow-up of the patients for the purpose of the early detection and timely correction of possible complications.
ARTICLE | doi:10.20944/preprints202001.0076.v2
Subject: Medicine & Pharmacology, Gastroenterology Keywords: endoscopic retrograde cholangiopancreatography; periampullary diverticulum; difficult cannulation; biliary cannulation; cannulation techniques; adverse events
Online: 17 January 2020 (04:12:23 CET)
Aim: This study aimed to investigate the association between periampullary diverticulum (PAD) and difficult biliary cannulation, as well as to evaluate the impact of different types of PAD on the cannulation success rate and adverse events. Methods: A total of 636 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) during the study period were prospectively studied and divided into two groups based on the presence or absence of PAD. In group A, 126 patients had PAD compared with 510 patients in group B without PAD. The primary outcome measurements were ERCP procedures time, selective cannulation techniques, and cannulation difficulty in addition to cannulation success rate and ERCP-related adverse events. The difficult cannulation was analyzed using logistic regression considering age, co-morbidities, the presence of PAD types, and indications as independent factors. Results: The average cohort age was 65.30±16.67 years, and 52.7% were male. Significant higher rates of choledocholithiasis, cholangitis, and biliary pancreatitis were reported in the group of PAD (p<0.05). Successful selective cannulation was achieved in 97.6% in group A and 95.3% in group B (p>0.05). The cannulation time was significantly longer in the presence of PAD (5.1 min, vs. 4.09 min, p<0.05). There was no significant difference in the rate of overall adverse events and post ERCP pancreatic PEP. Conclusion: The presence of PAD did not affect the duration or success of the ERCP procedure. Furthermore, it was associated with longer cannulation time and increase in the cannulation difficulty, especially with PAD type 1.
ARTICLE | doi:10.20944/preprints202007.0596.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-CoV-2; immunity; T cells; IL-6; GGT; hepatopathy; biliary lesion; acute kidney injury; liver disease
Online: 24 July 2020 (14:40:42 CEST)
The aim of this study was to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients which associated with mild, moderate, severe and fatal course of the disease and, through longitudinal follow-up, to understand the dynamics of COVID-19 pathophysiology. All SARS-CoV-2 positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. Severe course of COVID-19 was associated with elevation of proinflammatory markers, efflux of immature granulocytes into peripheral blood, activation of CD8 T cells, which infiltrate lungs, and transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with severe disease. In contrast, patients with fatal course of COVID-19 failed to upregulate markers of inflammation, showed dyscoordination of immune response and progressed towards acute kidney failure. COVID-19 is a disease with multi-organ affinity characterized by activation of innate and cellular adaptive immunity. Biliary lesion with elevation of GGT and organ-infiltration of IL-6 producing cells are defining characteristic for patients with fulminant disease.