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We present a case of haemobilia as a primary presentation for underlying cholangiocarcinoma. A man in his 50s initially presented to emergency with Quincke's triad, RUQ pain, jaundice and UGI bleeding. The initial diagnosis of haemobilia was made on endoscopic retrograde cholangiopancreatography (ERCP) on primary presentation, but the presence of blood and the recurrent clot obstruction of the biliary tract made the underlying diagnosis extremely difficult, resulting in the patient having 4 ERCP, 1 spyglass and multiple CTs and magnetic resonance cholangiopancreatography. Eventually, the patient underwent a Whipple's procedure without tissue diagnosis, confirming cholangiocarcinoma on histopathology. This case emphasises the difficulty of diagnosis of underlying malignancy in the setting of haemobilia, the benefit of multidisciplinary meeting discussions to support significant interventions and the need to be cautious and curious when managing atypical presentations., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mass-forming intrahepatic cholangiocarcinoma (mICC) is the most frequent type of ICC. In contrast-enhanced computed tomography, mICC is visualized as a hypodense lesion with distal dilatation of intrahepatic bile ducts. The presented case illustrates the unusual manifestation of mICC in a 71-year-old male patient, where despite the extensive tumor mass and the hilar infiltration, the dilatation of intrahepatic bile ducts and cholestasis were not noted., Methods: A literature review on PubMed was performed. Primarily, 547 records were identified, and the titles and abstracts were systematically searched. Regarding the inclusion and exclusion criteria, 31 papers describing the non-cancerous liver lesions mimicking ICC were included in the further analysis., Results: In 41.9% of the analyzed non-cancerous lesions, the obstruction of the bile ducts was not noted, similar to our patient. A significant cholestasis has been found in 30.03% of analyzed patients. The invasion of the liver hilum was noted in one-third of the patients., Conclusions: Atypical radiological features in lesions suspected of ICC, such as the absence of intrahepatic bile-duct dilation, are common in benign lesions. In the case of radiologically atypical lesions suspected of ICC, the diagnostic imaging needs to be correlated with clinical data, and the diagnosis should be confirmed with a pathological examination.

Background: Biliary obstruction before liver resection is a known risk factor for post-operative complications. The aim of this study was to determine the impact of persistent hyperbilirubinemia following preoperative biliary drainage before liver resection., Methods: The ACS-NSQIP (2016-2021) database was used to extract patients with cholangiocarcinoma who underwent anatomic liver resection with preoperative biliary drainage comparing those with persistent hyperbilirubinemia (> 1.2 mg/dL) to those with resolution. Patient characteristics and outcomes were compared with bivariate analysis. Multivariable modeling evaluated factors including persistent hyperbilirubinemia to evaluate their independent effect on serious complications, liver failure, and mortality., Results: We evaluated 463 patients with 217 (46.9%) having hyperbilirubinemia (HB) despite biliary stenting. Bivariate analysis demonstrated that patients with HB had a higher rate of serious complications than those with non-HB (80.7% vs 70.3%; P = 0.010) including bile leak (40.9% vs 31.8%; P = 0.045), liver failure (26.7% vs 17.9%; P = 0.022), and bleeding (48.4% vs 36.6%; P = 0.010). Multivariable analysis demonstrated that persistent HB was independently associated with serious complications (OR 1.88, P = 0.020) and mortality (OR 2.39, P = 0.049) but not post-operative liver failure (OR 1.65, P = 0.082)., Conclusions: Failed preoperative biliary decompression is a predictive factor for post-operative complications and mortality in patients undergoing hepatectomy and may be useful for preoperative risk stratification., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We report a case of a patient with distal bile duct cancer who presented with ocular pain and eye redness due to a liver abscess. The patient developed a liver abscess while waiting for surgery. Since Klebsiella pneumoniae with high viscosity was identified and imaging studies showed systemic infection, a diagnosis of klebsiella invasive syndrome was made. In addition, infectious intraocular inflammation was also observed at the same time. In addition to antibiotic therapy, vitrectomy and percutaneous transhepatic abscess drainage successfully normalized the inflammatory response and negative blood cultures were obtained. Thirty-four days after the start of treatment, surgery was performed and the postoperative course was uneventful, and the patient was discharged from the hospital on the 39th postoperative day. Forty-six months after that surgery, there has been no evidence of recurrence of cholangiocarcinoma or recurrence of infection, but unfortunately, vision loss in the right eye remains. Some Klebsiella pneumoniae are highly pathogenic and are often reported from Southeast Asia, and ocular pain and hyperemic symptoms are important physical findings., (© 2024. Japanese Society of Gastroenterology.)

The necessity of biliary drainage before pancreaticoduodenectomy remains controversial in cases involving malignant obstructive jaundice; however, the benefits of biliary drainage have been reported in cases with severe hyperbilirubinemia. Herein, we present the case of a 61-year-old man suffering from jaundice due to distal cholangiocarcinoma. In this case, obstructive jaundice was refractory to repeat endoscopic drainage and bilirubin adsorption. Hyperbilirubinemia persisted despite successful implementation of biliary endoscopic sphincterotomy and two rounds of plastic stent placements. Stent occlusion and migration were unlikely and oral cholagogues proved ineffective. Owing to the patient's surgical candidacy and his aversion to nasobiliary drainage due to discomfort, bilirubin adsorption was introduced as an alternative therapeutic intervention. Following repeated adsorption sessions, a gradual decline in serum total bilirubin levels was observed and pancreaticoduodenectomy was scheduled. The patient successfully underwent pancreaticoduodenectomy with portal vein resection and reconstruction and D2 lymph node dissection. After the surgery, the serum bilirubin levels gradually decreased and the patient remained alive, with no recurrence at 26 months postoperatively. Therefore, this case highlights the feasibility and safety of performing pancreaticoduodenectomy in patients with severe, refractory jaundice who have not responded to repeated endoscopic interventions and have partially responded to bilirubin adsorption., (© 2024. Japanese Society of Gastroenterology.)

Competing Interests: The authors have no conflicts of interest to declare.

The etiology of hemobilia has mainly iatrogenic (>50%), followed by traumatic causes. Others are biliopathy due to portal high pressure, or neoplastic or infective biliopathy. In the case of non-clear hemobilia, direct-vision-cholangioscopy can change the management in >34% of cases. Our patient had episodes of obstructive hemobilia with secondary cholangitis without objectifying underlying pathology. When she was referred to our center, SpyGlass®-cholangioscopy identified the suspicious lesion compatible with early-stage cholangiocarcinoma despite the diagnostic delay. In conclusion, it is important to keep in mind the neoformative etiology as a potential cause of hemobilia of unclear origin, in which case, cholangioscopy (SpyGlass®) can contribute to the recognition of the signs of malignancy of the lesion and, therefore, to the diagnosis.

Introduction: Previously we demonstrated that elevated serum CYFRA 21 - 1 is a reliable diagnostic and prognostic biomarker for biliary tract cancers. This study aims to explore the diagnostic performance of bile CYFRA 21 - 1 (bCYFRA 21 - 1) in discriminating malignant biliary obstruction (MBO) caused by cholangiocarcinoma (CCA)., Methods: 77 CCA patients ((17 intrahepatic CCA (iCCA), 49 perihilar CCA (pCCA) and 11 distal CCA (dCCA)) and 43 benign patients with biliary obstruction were enrolled. Serum and bile levels of CYFRA 21 - 1, carcinoembryonic antigen (CEA) and carbohydrate antigen 19 - 9 (CA19-9) were quantified. Diagnostic performances of these biomarkers were estimated by receiver operator characteristic curves. Subgroups analysis of these tumor markers among CCA subtypes was performed., Results: High bCYFRA 21 - 1 (cut-off value of 59.25 ng/mL with sensitivity of 0.889 and specificity of 0.750) and high bile to serum ratio of CYFRA 21 - 1 (b/sCYFRA 21 - 1, cut-off value of 31.55 with sensitivity of 0.741 and specificity of 0.778) achieved better diagnostic performance than any other biomarker in discriminating MBO. Subgroup analysis revealed that bCYFRA 21 - 1 was significantly elevated in all CCA subtypes; moreover b/sCYFRA 21 - 1 was upregulated in pCCA and dCCA (the mean b/sCYFRA 21 - 1 of pCCA was highest among CCA subtypes: 57.90, IQR 29.82-112.27)., Conclusions: Both high biliary CYFRA 21 - 1 and high bile to serum ratio of CYFRA 21 - 1 were reliable diagnostic biomarkers for MBO caused by CCA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Situs inversus totalis is a rare congenital malformation in which organs are positioned in a mirror-image relationship to normal conditions. It often presents with vascular and biliary malformations. Only a few reports have pointed out the surgical difficulties in patients with situs inversus totalis, especially in those with perihilar cholangiocarcinoma. This report describes a 66-year-old male patient who underwent left hemihepatectomy (S5, 6, 7, and 8) with combined resection of the caudate lobe (S1), extrahepatic bile duct, and regional lymph nodes for perihilar cholangiocarcinoma with situs inversus totalis. Cholangiocarcinoma was mainly located in the perihilar area and progressed extensively into the bile duct. Surgery was performed after careful evaluation of the unusual anatomy. Although several vascular anomalies required delicate manipulation, the procedures were performed without major intraoperative complications. Postoperatively, bile leakage occurred, but the patient recovered with drainage treatment. The patient was discharged on the 29th postoperative day. Adjuvant chemotherapy with S-1 was administered for approximately 6 months. There was no recurrence 15 months postoperatively. Appropriate imaging studies and an understanding of unusual anatomy make surgery safe and provide suitable treatment for patients with situs inversus totalis., (© 2024. Japanese Society of Gastroenterology.)

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient., (© 2024. The Author(s).)

Background: Sarcopenia is associated with adverse prognosis of intrahepatic cholangiocarcinoma (iCCA) after surgery., Methods: 321 patients with iCCA undergoing surgery were retrospectively recruited and assigned to training and validation cohort. Skeletal muscle index (SMI) was assessed to define sarcopenia. Logistic regression and cox regression analysis were used to identify risk factors. A novel sarcopenia-based nomogram was constructed and validated by ROC curves, calibration curves, and DCA curves., Results: 260 patients were included for analysis. The median age was 63.0 years and 161 patients (61.9%) were diagnosed with sarcopenia. Patients with sarcopenia exhibited a higher rate of postoperative complications, a worse OS and RFS than patients without sarcopenia. Sarcopenia, low albumin and intraoperative blood transfusion were independent risk factors of postoperative complications, while sarcopenia and low albumin were risk factors of high CCI≥26.2. Sarcopenia, high PS score, low-undifferentiated differentiation, perineural invasion, TNM stage III-IV were risk factors of OS, and a novel nomogram based on these five factors was built to predict the 12-, 24-, and 36-months OS, with the mean AUC > 0.6., Conclusion: Sarcopenia is negatively associated with both postoperative complications and survival prognosis of iCCA undergoing hepatectomy., (© 2024 Published by Elsevier Ltd.)

Background: The risk factors of patients with intrahepatic cholangiocarcinoma (ICC) requiring conversion to open surgery have not been adequately studied. This study aimed to determine the risk factors and postoperative outcomes of conversion in patients with ICC., Methods: From May 2014 to September 2022, Unplanned conversions were compared with successful LLRs., Results: 153 patients with ICC initially underwent LLR, of which 41 (26.8%) required conversion to open surgery. Multivariate analysis for those factors that were statistically significant or confirmed by clinical studies, tumor proximity to the major vessels (OR 6.643, P < 0.001), and previous upper abdominal surgery (OR 3.140, P = 0.040) were independent predictors of unplanned conversions. Compared to successful LLRs, unplanned conversions showed longer operative times (300.0 vs. 225.0 min, P < 0.001), more blood loss (500.0 vs. 200.0 mL, P < 0.001), higher transfusion rates (46.3% vs. 11.6%, P < 0.001), longer length of stays (13.0 vs. 8.0 days, P < 0.001), and higher rates of major morbidity (39.0% vs. 11.6%, P < 0.001). However, there was no statistically significant difference in 30-day or 90-day mortality between the conversion group and the laparoscopic group., Conclusion: Conversion during LLR should be anticipated in ICC patients with prior upper abdominal surgery or tumor proximity to major vessels as features., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To evaluate the efficacy and safety of biliary stenting implantation with iodine-125 seed strand (SI) followed by hepatic artery infusion chemotherapy (HAIC) plus lenvatinib (Len) with programmed death-1 (PD-1) inhibitor for patients diagnosed with extrahepatic cholangiocarcinoma (ECC) and malignant obstructive jaundice (MOJ)., Methods: In this single-center retrospective study, the data of ECC patients with MOJ from March 2015 to January 2023 was assessed. Using probability score matching (PSM), the selection bias of patients was reduced. Primary study outcomes included overall survival (OS) and progression-free survival (PFS). The OS and PFS were performed using the Kaplan-Meier method and evaluated with the log-rank test., Results: A total of 104 patients were enrolled finally, including 52 patients treated with interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor (SI+HAIC+Len+P group) and 52 patients treated with interventional therapy (SI+HAIC) plus lenvatinib (SI+HAIC+Len group). 26 pairs of patients were matched after PSM analysis. After PSM analysis, the median OS and PFS in the SI+HAIC+Len+P group were significantly longer compared to those in the SI+HAIC+Len group (OS:16.6 vs. 12.3 months, P = 0.001; PFS:12.6 vs 8.5 months, P = 0.004). The DCR was significantly different between groups ( P = 0.039), while ORR not ( P = 0.548). The addition of PD-1 inhibitor was generally well tolerated without treatment-associated mortality., Conclusion: Interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor was effective for ECC patients accompanied by MOJ with a manageable safety profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Ke, Chen, Yang, Huang and Wu.)

Background/aims: Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA., Methods: We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA., Results: During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02; p<0.001) was associated with poor overall survival., Conclusions: Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

Cholangiocarcinoma (CCA) is a prevalent cancer in Southeast Asia, with Opisthorchis viverrini (O.viverrini) infection being the primary risk factor. Most CCA cases in this region are diagnosed at advanced stages, leading to unfavorable prognoses. The development of stage-specific biomarkers for Opisthorchis viverrini-induced cholangiocarcinoma (Ov-CCA) holds crucial significance, as it facilitates early detection and timely administration of curative interventions, effectively mitigating the high morbidity and mortality rates associated with this disease in the Great Mekong region. Biomarkers are a promising approach for early detection, prognosis, and targeted treatment of CCA. Disease-specific biomarkers facilitate early detection and enable monitoring of therapy effectiveness, allowing for any necessary corrections. This review provides an overview of the potential O. viverrini-specific molecular biomarkers and important markers for diagnosing and monitoring Ov-CCA, discussing their prognostic, predictive, and diagnostic value. Despite the limited research in this domain, several potential biomarkers have been identified, encompassing both worm-induced and host-induced factors. This review offers a thorough examination of historical and contemporary progress in identifying biomarkers through multiomics techniques, along with their potential implications for early detection and treatment.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor and usually associated with a poor oncological prognosis. The current gold standard is the surgical resection of the tumor with subsequent adjuvant therapy. However, in case of irresectability e.g. in case of liver cirrhosis, a palliative treatment regime is conducted.This report demonstrates the case of an irresectable iCCA in liver cirrhosis due to primary sclerosing cholangitis (PSC) treated by living-donor liver transplantation (LDLT) facilitated by minimal invasive donor hepatectomy. No postoperative complications were observed in the donor and the donor was released on the 6 th postoperative day. Further, after a follow-up of 1.5 years, no disease recurrence was detected in the recipient.According to the recent international literature, liver transplantation can be evaluated in case of small solitary iCCA (< 3 cm) in cirrhosis. Less evidence is provided for transplantation in advanced tumors which are surgically not resectable due to advanced liver disease or infiltration of major vessels, however some reports display adequate long-term survival after strict patient selection. The selection criteria comprise the absence of distant metastases and locoregional lymph node metastases as well as partial remission or stable disease after neoadjuvant chemotherapy. Due to no established graft allocation for iCCA in Germany, LDLT is currently the best option to realize transplantation in these patients. Developments in the last decade indicate that LDLT should preferentially be performed in minimal invasive manner (laparoscopic or robotic) as this approach is associated with less overall complications and a shorter hospitalization. The presented case illustrates the possibilities of modern surgery and the introduction of transplant oncology in the modern therapy of patients combining systemic therapy, surgical resection and transplantation to achieve optimal long-term results in patients which were initially indicated for palliative treatment., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Cholangiocarcinoma is the second most common primary liver tumour worldwide with an increasing incidence in recent decades. While the effects of fibrosis on hepatocellular carcinoma have been widely demonstrated, the impact on cholangiocarcinoma remains unclear. The aim of this study was to evaluate the impact of liver fibrosis on overall survival (OS) and disease-free survival (DFS) in patients who have undergone liver resection for cholangiocarcinoma., Methods: Eighty patients with cholangiocarcinoma who underwent curatively intended liver surgery between January 2007 and December 2020 were included in this retrospective single-centre study. Clinical and histopathological features were analysed. The primary endpoint was cause-specific survival. Secondary endpoints were DFS and identification of prognostic factors., Results: The present study shows that the median OS is significantly reduced in patients with fibrosis (p &lt; 0.001). The median OS in patients with fibrosis was three times shorter than in the group without fibrosis. In addition, a significantly shorter DFS was observed in patients with fibrosis (p &lt; 0.002). Multivariate analysis showed that fibrosis is the strongest independent factor with a negative impact on OS and DFS., Conclusion: Liver fibrosis has a significant impact on OS and DFS in patients with cholangiocarcinoma. Patients with known liver fibrosis require thorough perioperative care and postoperative follow-up., (© 2024 S. Karger AG, Basel.)

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a liver tumor with features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It consists of intermingled malignant biliary and hepatic tissue and thus a distinct entity, rather than two separate coexisting malignancies. A 59-year-old female with a history of hepatitis C and cirrhosis presented with abdominal pain and altered mental status. She developed hematemesis, and despite extensive interventions, she expired one day after her initial presentation. At autopsy, the liver was diffusely and markedly fibrotic with numerous nodules of varying size with invasion into adjacent vasculature. Microscopic examination of the nodules revealed cHCC-CC with stem cell features, lymphovascular invasion, and tumor emboli scattered throughout the right lung. The patient had end-stage liver disease due to the accumulation of damage and consequent fibrosis. This led to portal hypertension with subsequent massive gastrointestinal bleeding, hemorrhagic shock, and death. cHCC-CC is a rare, aggressive primary liver tumor with a poor prognosis. It can present with a cirrhotomemetic pattern with small nodules that can evade clinical and radiographic detection. Autopsy findings can provide valuable insights into the pathogenesis and clinical course of cHCC-CC, highlight the aggressive nature of the disease, and may inform future diagnostic and therapeutic strategies. Accurate diagnosis of this tumor is important for patient management and prognostication., (© 2024 by the Association of Clinical Scientists, Inc.)

A 74-year-old female was admitted for painless jaundice. Laboratory tests showed hyperbilirubinemia, cholestasis, normal coagulation, and Ca19-9:163U/L. The CT-scan reported dilation of the intrahepatic and extrahepatic bile ducts secondary to a 24mm tumor in the intrapancreatic common bile duct. The magnetic cholangioresonance showed multiple endoluminal polypoid lesions, suggestive of intraductal papillary neoplasm of the bile duct (IPNB). The endoscopic bile duct brushing was non-conclusive.

Background: Cholangiocarcinoma (CCA) is a highly fatal tumor, and the most favorable chance for long-term survival lies in curative resection. Periductal fibrosis (PDF), a precancerous condition associated with chronic inflammation of the bile ducts, can serve as a screening marker for CCA using hepatobiliary ultrasonography (US). However, limited studies have explored the relationship between PDF and CCA. This study aimed to investigate the association between PDF and CCA in a population at risk in Northeast Thailand., Methods: The study included participants enrolled in the Cholangiocarcinoma Screening and Care Program (CASCAP) between 2013 and 2021 who underwent US. Histological evaluations were conducted following the standard protocol of the tertiary hospital at Khon Kaen University, Thailand. PDF was defined as the presence of fibrosis in the peripheral (PDF1), segmental (PDF2), or main bile duct (PDF3), diagnosed by well-trained general practitioners or radiologists. The association between PDF and CCA was assessed using multiple logistic regression, calculating adjusted odds ratios (AORs) and 95% confidence intervals (CIs)., Results: Out of 751,061 participants, the overall prevalence of PDF was 115,267 (15.35%), with an overall CCA rate of 0.11%. The rates of CCA were 0.1%, 0.15%, and 0.27% in participants with PDF1, PDF2, and PDF3, respectively. After adjusting for gender, age at enrollment, education levels, history of O. viverrini infection, smoking, and alcohol consumption, the AORs for CCA were 0.94 (95% CI: 0.74 - 1.20), 1.4 (95% CI: 1.03 - 1.91), and 2.52 (95% CI: 1.38 - 4.58) for participants with PDF1, PDF2, and PDF3, respectively., Conclusion: Our findings demonstrate a significant association between fibrosis of the segmental and main bile ducts (PDF2 and PDF3) and CCA, with the strongest association observed in participants with PDF3. Hepatobiliary US screening could serve as a valuable tool for early detection of CCA, enabling timely curative treatment.

Background: Cholestasis should be relieved by biliary drainage prior to major liver resection. This condition is often associated with bacterial colonization of the otherwise sterile biliary system. Cholangitis reduces the regenerative capacity of the remaining liver. Therefore, targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma (pCCC)., Methods: Between December 1999 and December 2017, 251 pCCC patients were treated in our center. In total, 115 patients underwent a microbiological analysis. In addition to the characterization of the specific microorganisms and antibiotic resistance, we analyzed subgroups according to preoperative intervention., Results: Enterococci (87/254, 34%) and Enterobacteria (65/254, 26%) were the most frequently detected genera. In 43% (50/115) of patients, Enterococcus faecalis was found in the bile duct sample. Enterococcus faecium (29/115) and Escherichia coli (29/115) were detected in 25% of patients. In patients with percutaneous transhepatic biliary drainage (3/8, 38%) or stents (24/79, 30%), Enterococcus faecium was diagnosed most frequently (P < 0.05). Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012 (P < 0.05). With regard to fungal colonization, the focus was on various Candida strains, but these strains generally lacked resistance., Conclusions: pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention. Specifically, targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection. In our cohort, the combination of meropenem and vancomycin represents an effective perioperative medical approach., (Copyright © 2022. Published by Elsevier B.V.)

Background: Body composition alterations are frequent in patients with cancer or chronic liver disease, but their prognostic value remains unclear in many cancer entities., Objective: We investigated the impact of disease aetiology and body composition after surgery for intrahepatic cholangiocarcinoma (iCCA), a rare and understudied cancer entity in European and North American cohorts., Methods: Computer tomography-based assessment of body composition at the level of the third lumbar vertebra was performed in 173 patients undergoing curative-intent liver resection for iCCA at the Department of Surgery, Charité - Universitätsmedizin Berlin. Muscle mass and -composition as well as subcutaneous and visceral adipose tissue quantity were determined semi-automatically. (Secondary) sarcopenia, sarcopenic obesity, myosteatosis, visceral and subcutaneous obesity were correlated to clinicopathological data., Results: Sarcopenia was associated with post-operative morbidity (intraoperative transfusions [p = 0.027], Clavien-Dindo ≥ IIIb complications [p = 0.030], post-operative comprehensive complication index, CCI [p < 0.001]). Inferior overall survival was noted in patients with myosteatosis (33 vs. 23 months, p = 0.020). Fifty-eight patients (34%) had metabolic (dysfunction)-associated fatty liver disease (MAFLD) and had a significantly higher incidence of sarcopenic (p = 0.006), visceral (p < 0.001) and subcutaneous obesity (p < 0.001). Patients with MAFLD had longer time-to-recurrence (median: 38 vs. 12 months, p = 0.025, log-rank test). Multivariable cox regression analysis confirmed only clinical, and not body, composition parameters (age > 65, fresh frozen plasma transfusions) as independently prognostic for overall survival., Conclusion: This study evidenced a high prevalence of MAFLD in iCCA, suggesting its potential contribution to disease aetiology. Alterations of muscle mass and adipose tissue were more frequent in patients with MAFLD., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The aim of the work described here was to investigate the value of dynamic contrast enhanced ultrasound (DCE-US) and quantitative analysis in pre-operative differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) in non-cirrhotic liver., Methods: In this retrospective study, patients with histopathologically proven ICC and HCC lesions in non-cirrhotic liver were included. All patients underwent contrast-enhanced ultrasound (CEUS) examinations with an Acuson Sequoia unit (Siemens Healthineers, Mountain View, CA, USA) unit or LOGIQ E20 (GE Healthcare, Milwaukee, WI, USA) within 1 wk before surgery. SonoVue (Bracco, Milan, Italy) was used as the contrast agent. B-mode ultrasound (BMUS) features and CEUS enhancement patterns were analyzed. DCE-US analysis was performed by VueBox software (Bracco). Two regions of interest (ROIs) were set in the center of the focal liver lesions and their surrounding liver parenchyma. Time-intensity curves (TICs) were generated, and quantitative perfusion parameters were obtained and compared between the ICC and HCC groups using the Student t-test or Mann-Whitney U-test., Results: From November 2020 to February 2022, patients with histopathologically confirmed ICC (n = 30) and HCC (n = 24) lesions in non-cirrhotic liver were included. During the arterial phase (AP) of CEUS, ICC lesions exhibited heterogeneous hyperenhancement (13/30, 43.3%), heterogeneous hypo-enhancement (2/30, 6.7 %) and rim-like hyperenhancement (15/30, 50.0%), whereas all HCC lesions exhibited heterogeneous hyperenhancement (24/24, 100.0%) (p < 0.05). Subsequently, most of the ICC lesions exhibited AP wash-out (83.3%, 25/30), whereas a few cases exhibited wash-out in the portal venous phase (PVP) (15.7%, 5/30). In contrast, HCC lesions exhibited AP wash-out (41.7%, 10/24), PVP wash-out (41.7%, 10/24) and a small part of late phase wash-out (16.7%, 4/24) (p < 0.05). Compared with those of HCC lesions, TICs of ICCs revealed earlier and lower enhancement during the AP, faster decline during the PVP and reduced area under the curve. The combined area under the receiver operating characteristic curve (AUROC) of all significant parameters was 0.946, with 86.7% sensitivity, 95.8% specificity and 90.7% accuracy in differential diagnosis between ICC and HCC lesions in non-cirrhotic liver, which improved the diagnostic efficacy of CEUS (58.3% sensitivity, 90.0% specificity and 75.9% accuracy)., Conclusion: ICC and HCC lesions in non-cirrhotic liver might exhibit some overlap of CEUS features in diagnosis. DCE-US with quantitative analysis would be helpful in pre-operative differential diagnosis., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Abstract: A 99m Tc-DPD bone scintigraphy with SPECT/CT was performed in a 64-year-old woman with intrahepatic cholangiocarcinoma to exclude osseous metastases. The images demonstrated central focal tracer uptake in the left lung without any visible morphological correlate in the low-dose CT scan. For further clarification, a contrast-enhanced CT scan was carried out, which revealed a subsegmental pulmonary artery embolism in the left lower lobe. Subsequently, the patient was therapeutically anticoagulated. This case highlights the importance of clarifying focal pulmonary uptake in order not to overlook concomitant diseases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

An 84-year-old female, with history of endometrial and gallbladder adenocarcinomas, both submitted to curative surgeries, was admitted to the emergency room with obstructive jaundice. Computed tomography and subsequent magnetic resonance cholangiopancreatography revealed a common hepatic duct stenosis with intrahepatic biliary dilatation. She underwent percutaneous transhepatic cholangiography with successful biliary drainage. During the same admission, the patient experienced episodes of hematochezia. Rectosigmoidoscopy showed a 20 mm ulcer in the distal rectum and congestion of the rectal mucosa. Computed tomography revealed rectal wall circumferential thickening. Ulcer biopsies were compatible with a neoplasia of biliary origin.

Case: Immune Checkpoint Inhibitors (ICIs) have dramatically revolutionized the therapeutic approaches by which we treat a series of cancers accompanied by immune-related adverse events (irAEs). Herein, we reported an intrahepatic cholangiocarcinoma male patient with a history of ankylosing spondylitis developing pulmonary arterial hypertension (PAH) under ICI combined therapy with pembrolizumab and lenvatinib. The indirect measurement of cardiac ultrasound showed a pulmonary artery pressure (PAP) of 72mmHg after 21 three-week cycles of ICI combined therapy. The patient partially responded to the treatment of glucocorticoid and mycophenolate mofetil. The PAP decreased to 55mmHg 3 months after the ICI combined therapy was discontinued, but increased to 90mmHg after the ICI combined therapy was rechallenged. We treated him with adalimumab -an antitumor necrosis factor-alpha (ani-TNF-α) antibody- combined with glucocorticoid and immunosuppressants under lenvatinib monotherapy. The patient responded again with PAP decreasing to 67mmHg after 2 two-week cycles of adalimumab. Accordingly, we diagnosed him to have irAE-related PAH. Our findings supported the use of glucocorticoid disease-modifying antirheumatic drugs (DMARDs) as a treatment option in refractory PAH.

Context: Cholangiocarcinoma (CCA), a malignancy of the biliary tract epithelium is of increasing importance due to its rising incidence worldwide. There is a lack of data on cirrhosis in intrahepatic CCA (iCCA) and how it affects overall survival and prognosis., Objectives: The primary objective of this study was to examine if there were differences in survival outcomes between iCCA patients with concomitant cirrhosis and those without cirrhosis., Methods: The National Cancer Database (NCDB) was used to identify and study patients with iCCA from 2004 to 2017. The presence of cirrhosis was defined using CS Site-Specific Factor 2 where 000 indicated no cirrhosis and 001 indicated the presence of cirrhosis. Descriptive statistics were utilized for patient demographics, disease staging, tumor, and treatment characteristics. Kaplan-Meier (KM) method with log-rank test and a multivariate logistic regression model was used to assess if the presence of cirrhosis in iCCA was associated with survival status and long-term survival (60 or more months after diagnosis)., Results: There were 33,160 patients with CCA in NCDB (2004-2017), of which 3644 patients were diagnosed with iCCA. One thousand fifty-two patients (28.9%) had cirrhosis as defined by Ishak Fibrosis score 5-6 on biopsy and 2592 patients (71.1%) did not meet the definition for cirrhosis. Although in univariate analyses using KM/log-rank tests showed a survival advantage for non-cirrhotic patients, there was no statistically significant association found between cirrhosis and survival status (OR = 0.82, p = 0.405) or long-term survival (OR = 0.98, p = 0.933) when multivariate analysis was used. iCCA patients with cirrhosis and Stage 1 tumor had the highest median OS (132 months) vs 73.7 months in the non-cirrhotic arm, while patients with stage IV disease who had cirrhosis had half the survival time of those without. Our data thus indicates that the presence of cirrhosis is not an independent prognostic factor for survival., (© 2023. The Author(s).)

Background/aim: Recently, the Global Leadership Initiative on Malnutrition (GLIM), which includes the world's leading clinical nutrition societies, proposed the first global diagnostic criteria for malnutrition. However, the association between malnutrition diagnosed by the GLIM criteria and prognosis in patients with resected extrahepatic cholangiocarcinoma (ECC) remains unknown. This study aimed to investigate the predictive validity of the GLIM criteria for the prognosis of patients with resected ECC., Patients and Methods: Between 2000 and 2020, 166 patients who underwent curative-intent resection for ECC were retrospectively analyzed. Prognostic significance of preoperative malnutrition diagnosed by the GLIM criteria was investigated using a multivariate Cox proportional hazards model., Results: Eighty-five (51.2%) and 46 (27.7%) patients were diagnosed with moderate and severe malnutrition, respectively. Increased malnutrition severity tended to be correlated with increased lymph node metastasis rate (p-for-trend=0.0381). The severe malnutrition group had worse 1-, 3-, and 5-year overall survival rates than the normal (without malnutrition) group (82.2% vs. 91.2%, 45.6% vs. 65.1%, 29.3% vs. 61.5%, respectively, p=0.0159). In multivariate analysis, preoperative severe malnutrition was an independent predictor for poor prognosis (hazard ratio=1.68, 95% confidence interval=1.06-2.66, p=0.0282), along with intraoperative blood loss >1,000 ml, lymph node metastasis, perineural invasion, and curability., Conclusion: Severe preoperative malnutrition diagnosed by the GLIM criteria was associated with poor prognosis in patients who underwent curative-intent resection for ECC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 61-year-old Japanese woman presented with epigastric pain and jaundice. Imaging showed the presence of primary distal cholangiocarcinoma (DCC). A subtotal stomach-preserving pancreaticoduodenectomy was performed, followed by chemotherapy using S-1. However, second-line chemotherapy with gemcitabine and cis-diamminedichloroplatinum was required for the treatment of hepatic metastasis of the DCC 3 months following the surgery. Nine months after the surgery, the serum calcium and parathyroid hormone-related peptide concentrations were high, at 16.5 mg/dL and 28.7 pmol/L, respectively, which suggested the presence of humoral hypercalcemia of malignancy (HHM) secondary to the DCC. Moreover, marked leukocytosis, with a white blood cell count of 40,400/μL, was also present. The patient died 11 months after the diagnosis of DCC. Because hypercalcemia of malignancy is associated with a poor prognosis, and HHM and leukocytosis caused by DCC are very rare, we have presented the present case in detail and provide a review of the existing literature.

Rationale: Wellens syndrome is a comprehensive electrocardiographic (ECG) diagnosis that combines medical history with characteristic ECG changes. These changes, characterized by biphasic T-wave inversions or symmetric and deep T-wave inversions in the anterior precordial leads, often indicate that the left anterior descending coronary artery is at a high risk of severe stenosis. Chemotherapy-related cardiovascular toxicity refers to damage to the cardiovascular system caused by chemotherapeutic drugs, which is unpredictable and may occur during or after chemotherapy., Patient Concerns: In this case report, a 41-year-old male patient with cholangiocarcinoma received sequential adjuvant chemotherapy with gemcitabine/nanoparticle albumin-bound paclitaxel and gemcitabine/cisplatin. This patient presented with recurrent brief chest pain episodes after the third dose of gemcitabine/cisplatin, and the characteristic T-wave morphological changes were captured in routine ECG monitoring prior to the 6th dose., Diagnoses: Acute coronary syndrome due to chemotherapy-related cardiovascular toxicity was diagnosed on the basis of characteristic ECG changes., Interventions: The patient underwent coronary angiography, which revealed diffuse stenosis of up to 95% in the middle segment of the left anterior descending coronary artery. Stents were implanted in the stenotic segment for vascular reconstruction., Outcomes: The patient's chest pain was completely resolved, and electrocardiography returned to normal., Lessons: Cardiovascular toxicity during chemotherapy in patients with cancer may be life threatening. This rare case highlights the importance of identifying the characteristic ECG pattern of the Wellens syndrome by monitoring electrocardiography during chemotherapy. Immediate and accurate identification of the morphological ECG features of Wellens syndrome with a slight elevation of the ST-segment is related to patient prognosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pemigatinib is a fibroblast growth factor receptor inhibitor (FGFRi) approved for the treatment of patients with previously treated biliary tract cancer with FGFR2 fusion. Although infrequent, ocular toxicity manifested as serous retinal detachment (SRD) has been observed and is regarded as a serious side effect. We herein report the case of a 54-year-old woman with unresectable cholangiocarcinoma-initiated pemigatinib after failure of gemcitabine plus S-1 (GS). Although the patient experienced repeated SRD after pemigatinib, dose interruption and dose reduction of pemigatinib from 13.5 mg to 9 mg, and from 9 mg to 4.5 mg led to complete recovery of SRD, and continued tumor shrinkage.

Background: Laparoscopic liver resection (LLR) is controversial in treating intrahepatic cholangiocarcinoma (ICC). Therefore, this study aimed to evaluate the safety and feasibility of LLR for the treatment of ICC and explored the independent factors affecting the long-term prognosis of ICC., Methods: We included 170 patients undergoing hepatectomy for ICC from December 2010 to December 2021 and divided them into LLR group and open liver resection (OLR) group. We used propensity score matching (PSM) analysis to reduce the impact of data bias and confounding variables and then compared the short-term and long-term prognosis of LLR and OLR in treating ICC; Cox proportional hazards regression model was adopted to explore the independent factors affecting the long-term prognosis of ICC., Results: A total of 105 patients (70 in the LLR group and 35 in the OLR group) were included after 2:1 PSM analysis. There was no difference in demographic characteristics and preoperative indexes between the two groups. The perioperative results of the OLR group were worse than those of the LLR group, that is, the intraoperative blood transfusion rate (24 (68.6) vs 21 (30.0)), blood loss (500 (200-1500) vs 200 (100-525)), and the morbidity of major postoperative complications (9 (25.7) vs 6 (8.5)) in the OLR group were worse than those in LLR group. LLR could enable patients to obtain an equivalent long-term prognosis compared to OLR. The Cox proportional hazards regression model exhibited that no matter before or after PSM, preoperative serum CA12-5 and postoperative hospital stay were independent factors affecting overall survival, while only lymph node metastasis independently influenced recurrence-free survival., Conclusions: Compared with ICC treated by OLR, the LLR group obtained superior perioperative period outcomes. In the long run, LLR could enable ICC patients to receive an equivalent long-term prognosis compared to OLR. In addition, ICC patients with preoperative abnormal CA12-5, lymph node metastasis, and more extended postoperative hospital stay might suffer from a worse long-term prognosis. However, these conclusions still need multicenter extensive sample prospective research to demonstrate., (© 2023. The Author(s).)

Background: The appropriate method of preoperative endoscopic biliary drainage (EBD) for cholangiocarcinoma with hilar biliary obstruction remains controversial. The inside-stent technique is a method of placing plastic stents entirely inside the bile duct. Several studies of patients with unresectable stage have reported longer stent patency compared with conventional endoscopic biliary stenting (EBS). Inside-stent techniques have been introduced as a bridge-to-surgery option and as an alternative to conventional EBS., Aims: We aimed to evaluate the clinical outcomes of inside stent use and conventional EBS., Methods: During this retrospective multicenter study, we reviewed consecutive patients with cholangiocarcinoma who underwent radical surgery after conventional EBS or inside-stent insertion. Adverse event (AE) rates after EBD and post-surgical AEs were compared. A multivariable analysis was performed to identify factors affecting cholangitis after EBD., Results: Conventional EBS and inside-stent procedures were performed for 56 and 73 patients, respectively. Patient backgrounds were similar between groups, except for percutaneous transhepatic portal vein embolization. The waiting time before surgery was similar between groups (28.5 days vs. 30 days). There were no significant differences in the cholangitis rate (21.4% vs. 26.0%; P = 0.68) and all AEs (25.0% vs. 30.1%; P = 0.56) between groups. The post-surgical AE rate was similar between the groups. The multivariable analysis found that preprocedural cholangitis was a risk factor for cholangitis after EBD (odds ratio: 5.67; 95% confidence interval: 1.61-19.9)., Conclusions: The outcomes of inside-stent techniques and conventional EBS for the management of preoperative EBD are comparable for patients with cholangiocarcinoma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metabolic syndrome (MetS) is a common condition closely associated with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Recent meta-analyses show that MetS can be prodromal to intrahepatic cholangiocarcinoma (iCCA) development, a liver tumor with features of biliary differentiation characterized by dense extracellular matrix (ECM) deposition. Since ECM remodeling is a key event in the vascular complications of MetS, we aimed at evaluating whether MetS patients with iCCA present qualitative and quantitative changes in the ECM able to incite biliary tumorigenesis. In 22 iCCAs with MetS undergoing surgical resection, we found a significantly increased deposition of osteopontin (OPN), tenascin C (TnC), and periostin (POSTN) compared to the matched peritumoral areas. Moreover, OPN deposition in MetS iCCAs was also significantly increased when compared to iCCA samples without MetS (non-MetS iCCAs, n = 44). OPN, TnC, and POSTN significantly stimulated cell motility and the cancer-stem-cell-like phenotype in HuCCT-1 (human iCCA cell line). In MetS iCCAs, fibrosis distribution and components differed quantitatively and qualitatively from non-MetS iCCAs. We therefore propose overexpression of OPN as a distinctive trait of MetS iCCA. Since OPN stimulates malignant properties of iCCA cells, it may provide an interesting predictive biomarker and a putative therapeutic target in MetS patients with iCCA.

Background and Aims: Differentiation of benign and malignant biliary tract strictures on brush material remains highly challenging but is essential for adequate clinical management of patients with primary sclerosing cholangitis (PSC). In this case-control study, biliary brush cytology samples from PSC patients with cholangiocarcinoma (PSC-CCA) were compared with samples from PSC patients without CCA (PSC-control subjects) using next-generation sequencing (NGS)., Methods: Cells on archived slides were dissected for DNA extraction. NGS was performed using a gene panel containing 242 hotspots in 14 genes. Repeated brush samples from the same patient were analyzed to study the consistency of NGS results. In PSC-CCA cases that underwent surgical resection, molecular aberrations in brush samples were compared with NGS data from subsequent resection specimens., Results: Forty patients (20 PSC-CCA and 20 PSC-control subjects) were included. The gene panel detected 22 mutations in 15 of 20 PSC-CCA brush samples, including mutations in TP53 (8 brush samples), K-ras (5), G-nas (3), ERBB2 (1), APC (1), PIK3CA (1), and SMAD4 (1). One G-nas and 3 K-ras mutations were found in 3 of 20 PSC-control brush samples. The sensitivity of the NGS panel was 75% (95% confidence interval, 62%-80%) and specificity 85% (95% confidence interval, 64%-95%). Repeated brush samples showed identical mutations in 6 of 9 cases. Three repeated brush samples demonstrated additional mutations as compared with the first brush sample. In 6 of 7 patients, mutations in brush samples were identical to mutations in subsequent resection specimens., Conclusions: NGS mutation analysis of PSC brush cytology detects oncogenic mutations with high sensitivity and specificity and seems to constitute a valuable adjunct to cytologic assessment of brush samples., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Cholangiocarcinoma (CCA), a fatal bile duct cancer, has a high incidence in Western Siberia, Russian Federation. In addition, Opisthorchis felineus, a bile duct-dwelling trematode liver fluke is highly endemic. Closely related species have been shown to be cancerogenic agents in Asia. We therefore examined the association between O felineus infection and CCA in Western Siberia., Methods: We conducted a hospital-based, individually matched case-control study between January 2017 and August 2020 in Tomsk Oblast and Khanty-Mansiysk Autonomous Okrug, Yugra, Russian Federation. Histologically confirmed CCA patients (cases) were compared with matched age, sex, and place of residence hospital controls. The examination of study participants included the diagnosis of current and past O felineus infection, abdominal ultrasonographical assessment, physical examination, and interview on exposures to potential risk factors., Results: We identified 40 patients with CCA and 160 controls. Exposures to O felineus infection was strongly associated with CCA (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4-10.8; P = .008). Also, cases reported more often that they were currently or in the past were infected by O felineus compared with controls (OR, 4.03; 95% CI, 1.7-9.5; P = .001). Furthermore, cases reported river fish consumption and fishing habits significantly more often than controls (OR, 5.5; 95% CI, 1.5-19.8; P = .009 and OR, 3.3; 95% CI, 1.4-7.7; P = .005)., Conclusions: The study results revealed a strong significantly increased risk for CCA development in O felineus-infected individuals. Elaboration of the guidelines on screening programs for early CCA diagnosis, prevention, and treatment is socially important in endemic regions., Competing Interests: Potential conflicts of interest. P. O. reports a grant from University of Geneva to plan and implement a collaborative course in epidemiology between Swiss TPH and the Siberian State Medical University outside of the submitted work. All other authors have no conflicts of interest to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The treatment of choice for a resectable hilar cholangiocarcinoma is hepatectomy. Alternative treatment for unresectable cases includes liver transplantation;however, curative surgery is hindered by a distal cholangiocarcinoma extension into the intrapancreatic duct. Herein, we present a case of simultaneous living donor liver transplantation and pancreaticoduodenectomy for an extensive cholangiocarcinoma that is associated with primary sclerosing cholangitis, involving the perihilar and intrapancreatic duct. The treatment strategy involved neoadjuvant chemotherapy and radiation therapy, an exploratory laparoscopy and laparotomy for accurate staging, en-bloc whole bile duct and hepatoduodenal ligament resection, portal vein reconstruction with an interposition graft, and arterial reconstruction with the middle colic artery. The patient was discharged 122 days postoperatively although she suffered from postoperative ascites and delayed gastric emptying. Simultaneous living donor liver transplantation and pancreatoduodenectomy should be considered as treatment options for advanced cholangiocarcinoma.

An 87-year-old man visited his previous doctor because of jaundice, abdominal pain, and disturbance of consciousness. He was diagnosed with cholangitis and panperitonitis and was referred to our hospital. Emergency laparotomy revealed biliary peritonitis. However, the bile leak point was unclear. Two days after surgery, endoscopic retrograde cholangiopancreatography was performed and revealed hilar bile duct stenosis, slight dilation of the intrahepatic bile duct, and bile leakage from the peripheral left intrahepatic bile duct to the abdominal free space. Endoscopic nasobiliary drainage was performed, and bile leakage decreased. He was discharged from our hospital with improvement from jaundice and peritonitis. Intrahepatic bile duct rupture with neoplastic obstruction of the bile duct is extremely rare. To date, only two cases of intrahepatic bile duct rupture with intrahepatic cholangiocarcinoma have been published.

Purpose: The concept of osteosarcopenia, which is concomitant osteopenia and sarcopenia, has been proposed as a prognostic indicator for cancer patients. The aim of this study was to evaluate the prognostic significance of osteosarcopenia in patients with intrahepatic cholangiocarcinoma (IHCC)., Methods: The subjects of this retrospective study were 41 patients who underwent hepatic resection for IHCC. Osteopenia was assessed with pixel density in the mid-vertebral core of the 11th thoracic vertebra and sarcopenia was assessed by the psoas muscle areas at the third lumbar vertebra. Osteosarcopenia was defined as the concomitant occurrence of osteopenia and sarcopenia. We analyzed the association of osteosarcopenia with disease-free and overall survival and evaluated clinicopathologic variables in relation to the osteosarcopenia., Results: Eighteen (44%) of the 41 patients had osteosarcopenia. Multivariate analysis identified osteosarcopenia (hazard ratio 3.38, 95% confidence interval: 1.49-7.68, p < 0.01) as an independent predictor of disease-free survival, and age ≥ 65 years (p = 0.03) and osteosarcopenia (hazard ratio 6.46, 95% confidence interval: 1.76-23.71, p < 0.01) as independent predictors of overall survival., Conclusions: Preoperative osteosarcopenia may be a predictor of adverse prognosis for patients undergoing hepatic resection for IHCC, suggesting that preoperative management to maintain muscle and bone intensity could improve the prognosis., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Introduction: Wernicke's encephalopathy, a disorder caused by thiamin deficiency, is characterized by a classical triad of encephalopathy, ataxia, and ophthalmoplegia. Although alcoholism is the most common predisposing factor, it can also be associated with nonalcoholic states (hyperemesis gravidarum, intestinal obstruction, bariatric surgery, and others). This work presents a case of nonalcoholic Wernicke-Korsakoff syndrome diagnosed in a cholangiocellular carcinoma patient and literature review., Case Report: A 65-year-old male patient with a history of cholangiocellular carcinoma (Klatskin tumor) was treated with radiotherapy at the operation site after Roux-en-Y hepaticojejunostomy. During follow-up, the patient developed gastric outlet obstruction and was diagnosed with peritoneal carcinomatosis after a palliative gastrojejunostomy. As the patient could not tolerate oral nutrition during hospitalization, total parenteral nutrition was administered. After 10 days of admission, the patient showed decreased response to verbal stimuli as well as bilateral horizontal nystagmus, lethargy, and disorientation. Furthermore, the patient displayed confabulation. Clinical and imaging findings were consistent with Wernicke's encephalopathy. Therefore, treatment with intravenous thiamin replacement was initiated. The patient's encephalopathy regressed on the second day after treatment, and he recovered the place-person-time orientation. In the following month, the abnormal imaging findings were almost entirely resolved., Conclusion: In order to prevent irreversible brain damage induced by chronic thiamin deficiency, thiamin replacement therapy with parenteral nutrition solutions should be included as a treatment for hospitalized cancer patients unable to receive enteral nutrition for a long time., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

We present a rare case of combined hepatocellular carcinoma-cholangiocarcinoma in a woman with a history of univentricular congenital heart disease requiring multiple corrective operations including Fontan procedure. During workup for elevated alpha fetal protein, a right hepatic lobe lesion was identified with biopsy showing poorly differentiated hepatocellular carcinoma. She underwent successful segment 5 liver resection. Final pathology demonstrated combined hepatocellular carcinoma-cholangiocarcinoma. She was treated with gemcitabine/oxaliplatin adjuvant chemotherapy and had no evidence of recurrent disease at her 12-month follow-up. To our knowledge, this is the first case reported in of successful treatment of this rare malignancy in the setting of Fontan-associated liver disease and highlights the importance of a robust screening protocol in this patient population. Semiannual screening for the development of primary liver malignancy should start by 10 years post-Fontan and continue until heart-liver transplantation may be performed. It is important to note that cirrhosis is not a pre-requisite for the development of hepatocellular carcinoma or cholangiocarcinoma in these patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cholangiocarcinoma (CCA) is a primary hepatic tumor, frequently found in patients with liver cirrhosis and biliary tract diseases. Its varieties include isolated CCA or "combined hepatocellular-cholangiocarcinoma" (cHCC-CCA). The latter is uncommon, with poorly defined diagnostic criteria and natural history., Aim: To characterize patients with cirrhosis with a pathological diagnosis of CCA and cHCC-CCA., Material and Methods: Forty-nine liver biopsies with a pathological diagnosis of CCA were reviewed. The clinical records of patients were reviewed to fetch demographic variables, etiology of cirrhosis and clinical presentation., Results: Eight of the 49 patients had cirrhosis (16% of CCA biopsies reviewed). Their median age was 64 (27-71) years and five were females. Four patients had CCA, three patients cHCC-CCA and one had a bifocal tumor. Patients in the CCA group were more commonly symptomatic. Alpha-fetoprotein and CA 19-9 levels were elevated in one of eight and four of six patients, respectively. Within 12 months from diagnosis, five of eight patients died., Conclusions: In most of these cases, the diagnosis of cHCC-CCA and CCA was made in the liver explant study without previous imaging diagnosis. This reinforces the usefulness of the histological study, in specific cases, prior to liver transplantation and emphasizes the importance of systematic explant exploration in these cases.

Background and Aims: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population., Methods: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers., Results: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival., Conclusion: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant., (© 2022. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.