PERCUTANEOUS CHOLANGIOSCOPY AND LASER BILIARY LITHOTRIPSY FOR BILIARY INTRAHEPATIC STONES MANAGEMENT: CASE REPORT.

Intrahepatic biliary stone disease is a difficult condition to treat, due to anatomical complexity of biliary tract, association with colestasis, and high recurrence rates, with potential short- and long-term complications, such as cholangitis and secondary biliary cirrhosis. Removal of biliary stones via intraductal access can be achieved endoscopically or percutaneously, with preference for cholangioscopy-guided laser lithotripsy in complex cases. The surgical approach, despite its prolonged results, is a more invasive and risky procedure. The authors present a case of cholangioscopy with percutaneous laser biliary lithotripsy as an option for the treatment of intrahepatic biliary stone disease associated with biliary stricture following biliodigestive anastomosis due to bile duct injury following cholecystectomy, a safe and effective alternative with low morbidity and satisfactory outcomes in follow-up.

[Magnetic resonance imaging features and classification of intraductal papillary neoplasm of the bile duct].

Objective: To explore the magnetic resonance imaging (MRI) features and classification of intraductal papillary neoplasm of the bile duct (IPNB). Methods: Data from 90 patients with intraductal papillary neoplasm of the bile duct confirmed pathologically between June 2010 and January 2023 were retrospectively analyzed. The image analysis included the shape and location of the tumor, whether bile ducts had dilatation and the degree of dilation, whether there was a history of liver disease, whether there was a history of schistosomiasis, whether there was cancerous transformation, whether there were concurrent bile duct stones, whether there was hepatic lobe atrophy, whether there was hilar or abdominal lymph node enlargement, whether there was invasion of the bile duct wall, whether there was invasion of surrounding blood vessels, whether the tumor appears on T1-and T2 weighted imaging (T(1)WI and T(2)WI), whether the diffusion was limited, whether there was concurrent bleeding, enhancement rate, and whether there was abdominal fluid accumulation. Intraductal papillary neoplasms of the bile duct were divided into four types according to the morphological classification standards: type I (local bile duct dilation), type II (cystic), type III (free tumor), and type IV (dilated bile duct). The differences in the clinical and MRI features of the four groups of lesions were analyzed. Statistical analysis was performed with a t-test, an analysis of variance, and an χ(2)-test according to the different data. Results: Among the 90 cases with hepatic IPNB, there were 31 cases of type I, 15 cases of type II, 16 cases of type III, and 28 cases of type IV, 41 cases of liver left lobe, 11 cases of right and left lobe liver span, 7 cases of liver right lobes, 2 cases of liver caudate lobe, and 13 cases of hepatic hilar. There were statistically significant differences between the four groups (P < 0.05) in terms of age, clinical symptoms, direct bilirubin, γ-glutamyltransferase, whether they were cancerous, whether they were combined with bile duct stones, whether the liver lobes were atrophying, whether there was limited diffusion, intrahepatic bile duct diameter, and common bile duct diameter. However, there were no statistically significant differences among the four groups in gender, location, carbohydrate antigen 19-9, history of liver disease, history of schistosomiasis, carcinoembryonic antigen, alanine aminotransferase, aspartate aminotransferase, total bilirubin, whether hemorrhage was associated, lesion enhancement rate, whether the hilar/retroperitoneal lymph node was enlarged, whether the bile duct wall was invaded, whether blood vessels were invaded, and whether abdominal fluid was accumulated (P > 0.05). Conclusion: MRI manifestations have certain features for different types of intraductal papillary neoplasm of the bile duct tumors; hence, MRI aids in the diagnosis and differential diagnosis of this disease.

Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma: A report of 3 cases and literature review. / Epstein-Barrç— æ¯’ç›¸å ³æ·‹å·´ä¸Šçš®ç˜¤æ ·è‚å† èƒ†ç®¡ç™Œ3ä¾‹å¹¶æ–‡çŒ®å¤ä¹ ï¼ˆè‹±æ–‡ï¼‰.

Hepatic lymphoepithelioma-like carcinoma (LELC) is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant lymphatic infiltration. Hepatic LELC mainly includes lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) and lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-CC). Epstein-Barr virus (EBV) infection is considered as an important factor in LELC carcinogenesis. Since 2005, Xiangya Hospital of Central South University has treated a total of 3 patients with EBV-associated LEL-CC, which all showed liver masses by CT scans. After surgical resection, the EBV encoded RNA (EBER) and CK19 expression in all 3 patients were positive, and pathological examination confirmed EBV-associated LEL-CC. Two patients had a good postoperative prognosis, while 1 patient received relevant immunotherapy and chemotherapy after surgery. Based on the analysis of existing literature, the author believes that hepatic LELC can be included in the classification of liver tumors, which will provide new ideas for the accurate diagnosis and treatment of hepatic LELC.

What is the appropriate method of pathological specimen collection for cholangiocarcinoma detection in primary sclerosing cholangitis?

BACKGROUND: In primary sclerosing cholangitis (PSC), it is important to understand the cholangiographic findings suggestive of malignancy, but it is difficult to determine whether cholangiocarcinoma is present due to modifications caused by inflammation. This study aimed to clarify the appropriate method of pathological specimen collection during endoscopic retrograde cholangiopancreatography for surveillance of PSC. METHODS: A retrospective observational study was performed on 59 patients with PSC. The endpoints were diagnostic performance for benign or malignant on bile cytology and transpapillary bile duct biopsy, cholangiographic findings of biopsied bile ducts, diameters of the strictures and upstream bile ducts, and their differences. RESULTS: The sensitivity (77.8% vs. 14.3%, P = 0.04), specificity (97.8% vs. 83.0%, P = 0.04), and accuracy (94.5% vs. 74.1%, P = 0.007) were all significantly greater for bile duct biopsy than for bile cytology. All patients with cholangiocarcinoma with bile duct stricture presented with dominant stricture (DS). The diameter of the upstream bile ducts (7.1 (4.2-7.2) mm vs. 2.1 (1.2-4.1) mm, P < 0.001) and the diameter differences (6.6 (3.1-7) mm vs. 1.5 (0.2-3.6) mm, P < 0.001) were significantly greater in the cholangiocarcinoma group than in the noncholangiocarcinoma group with DS. For diameter differences, the optimal cutoff value for the diagnosis of benign or malignant was 5.1 mm (area under the curve = 0.972). CONCLUSION: Transpapillary bile duct biopsy should be performed via localized DS with upstream dilation for the detection of cholangiocarcinoma in patients with PSC. Especially when the diameter differences are greater than 5 mm, the development of cholangiocarcinoma should be strongly suspected.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

A case report of perihilar cholangiocarcinoma in a patient with situs inversus totalis.

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.

Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct.

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Prognostic Impact of Visceral Adipose Tissue Imaging Parameters in Patients with Cholangiocarcinoma after Surgical Resection.

Visceral adiposity is known to be related to poor prognosis in patients with cholangiocarcinoma; however, the prognostic significance of the qualitative features of adipose tissue in cholangiocarcinoma has yet to be well defined. This study investigated the prognostic impact of adipose tissue imaging parameters reflecting the quantity and qualitative characteristics of subcutaneous (SAT) and visceral (VAT) adipose tissue on recurrence-free survival (RFS) and overall survival (OS) in 94 patients undergoing resection of cholangiocarcinoma. The area, mean computed tomography (CT) attenuation, and mean 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of SAT and VAT on positron emission tomography (PET)/CT for staging work-up were measured, and the relationship of these adipose tissue imaging parameters with clinicopathological factors and survival was assessed. TNM stage, histologic grade, lymphovascular invasion, and the size of cholangiocarcinoma showed positive correlations with adipose tissue imaging parameters. Multivariate survival analysis demonstrated that the visceral-to-subcutaneous adipose tissue area ratio (VSR) (p = 0.024; hazard ratio, 1.718) and mean FDG uptake of VAT (p = 0.033; hazard ratio, 9.781) were significant predictors for RFS, but all of the adipose tissue imaging parameters failed to show statistical significance for predicting OS. In addition to visceral adiposity, FDG uptake of VAT might be a promising prognostic parameter for predicting RFS in patients with cholangiocarcinoma.

Novel definition of textbook outcome in biliary system cancers and its influence on patients' survival and quality of life.

BACKGROUND: The definition of textbook outcome in biliary system cancers is a developing concept in need of expansion and investigation of its association with survival and quality of life. METHODS: In this original research, we developed a novel "all or none" textbook outcome definition which addresses the rapid recovery of post-surgical indexes, in addition to short-term mortality, hospital re-admission, prolonged stay, surgical margin and postoperative complications. Based on the fulfillment of relevant criteria, patients were divided into textbook outcome and non-textbook outcome groups and their characteristics and survival data were analyzed. A customized "quality of life" questionnaire was developed to address short-term recovery and post-discharge life quality of patients. Association with quality of life improvement was then investigated. RESULTS: A total of 129 patients were included. Textbook outcome was achieved in 25.58% of patients (37.04% of gallbladder cancer patients and 17.8% of cholangiocarcinoma patients). Compared to non-textbook outcome group, patients with textbook outcome had lower rate of pre-operative biliary drainage (p = 0.026), higher rate of normal preoperative liver function (p < 0.001) and tumor markers (p = 0.001), reduced perioperative bleeding (p = 0.006) and blood transfusion (p = 0.005), and higher rate of N0 stage cases (p = 0.008). Textbook outcome was also associated with enhanced survival, significantly in older patients (<65 years) (1-year survival rate: 100% vs. 78.57% (p = 0.108), 2-year survival rate: 87.5% vs. 44% (p = 0.046)). Finally, textbook outcome was significantly associated with enhanced basic daily performance (p < 0.001), social life performance (p = 0.033), and personal evaluation (p < 0.001), and thus improved quality of life (p < 0.001). CONCLUSIONS: The novel definition of textbook outcome was able to address the specific nature of recovery after resection of biliary system cancers. Expanding the scope of textbook outcome and addressing the influence on survival and quality of life provides a comprehensive concept able to reflect physical, psychological and functioning enhancements in patients recovery.

Medicaid expansion and palliative care for advanced-stage liver cancer.

BACKGROUND: Medicaid expansion (ME) has contributed to transforming the United States healthcare system. However, its effect on palliative care of primary liver cancers remains unknown. This study aimed to evaluate the association between ME and the receipt of palliative treatment in advanced-stage liver cancer. METHODS: Patients diagnosed with stage IV hepatocellular carcinoma or intrahepatic cholangiocarcinoma were identified from the National Cancer Database and divided into pre-expansion (2010-2013) and postexpansion (2015-2019) cohorts. Logistic regression identified predictors of palliative treatment. Difference-in-difference (DID) analysis assessed changes in palliative care use between patients living in ME states and patients living in non-ME states. RESULTS: Among 12,516 patients, 4582 (36.6%) were diagnosed before expansion, and 7934 (63.6%) were diagnosed after expansion. Overall, rates of palliative treatment increased after ME (18.1% [pre-expansion] vs 22.3% [postexpansion]; P < .001) and are more pronounced among ME states. Before expansion, only cancer type and education attainment were associated with the receipt of palliative treatment. Conversely, after expansion, race, insurance, location, cancer type, and ME status (odds ratio [OR], 1.23; 95% CI, 1.06-1.44; P = .018) were all associated with palliative care. Interestingly, the odds were higher if treatment involved receipt of pain management (OR, 2.05; 95% CI, 1.23-2.43; P = .006). Adjusted DID analysis confirmed increased rates of palliative treatment among patients living in ME states relative to non-ME states (DID, 4.4%; 95% CI, 1.2-7.7; P = .008); however, racial disparities persist (White, 5.6; 95% CI, 1.4-9.8; P = .009; minority, 2.6; 95% CI, -2.5 to 7.6; P = .333). CONCLUSION: The implementation of ME contributed to increased rates of palliative treatment for patients residing in ME states after expansion. However, racial disparities persist even after ME, resulting in inequitable access to palliative care.

Babaodan overcomes cisplatin resistance in cholangiocarcinoma via inhibiting YAP1.

CONTEXT: Cholangiocarcinoma with highly heterogeneous, aggressive, and multidrug resistance has a poor prognosis. Although babaodan (BBD) combined with cisplatin improved non-small cell lung cancer efficacy, its impact on overcoming resistance in cholangiocarcinoma remains unexplored. OBJECTIVE: This study explored the role and mechanism of BBD on cisplatin resistance in cholangiocarcinoma cells (CCAs). MATERIALS AND METHODS: Cisplatin-resistant CCAs were exposed to varying concentrations of cisplatin (25-400 µg/mL) or BBD (0.25-1.00 mg/mL) for 48 h. IC50 values, inhibition ratios, apoptosis levels, DNA damage, glutathione (GSH) levels, oxidized forms of GSH, total GSH content, and glutaminase relative activity were evaluated using the cell counting kit 8, flow cytometry, comet assay, and relevant assay kits. RESULTS: BBD-reduced the cisplatin IC50 in CCAs from 118.8 to 61.83 µg/mL, leading to increased inhibition rate, apoptosis, and DNA damage, and decreased expression of B-cell lymphoma-2, p-Yes-associated protein 1/Yes-associated protein 1, solute carrier family 1 member 5, activating transcription factor 4, and ERCC excision repair 1 in a dose-dependent manner with maximum reductions of 78.97%, 51.98%, 54.03%, 56.59%, and 63.22%, respectively; bcl2-associated X and gamma histone levels were increased by 0.43-115.77% and 22.15-53.39%. The impact of YAP1 knockdown on cisplatin-resistant CCAs resembled BBD. GSH, oxidized GSH species, total GSH content, and glutaminase activity in cisplatin-resistant CCAs with BBD treatment also decreased, while YAP1 overexpression countered BBD's effects. DISCUSSION AND CONCLUSION: This study provides a scientific basis for BBD clinical application and provides a new direction for BBD biological mechanism research.

RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated ß-catenin signaling in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary tract cancer. Our previous CCA mutation pattern study focused on genes in the post-transcription modification process, among which the alternative splicing factor RBM10 captured our attention. However, the roles of RBM10 wild type and mutations in CCA remain unclear. METHODS: RBM10 mutation spectrum in CCA was clarified using our initial data and other CCA genomic datasets from domestic and international sources. Real-time PCR and tissue microarray were used to detect RBM10 clinical association. Function assays were conducted to investigate the effects of RBM10 wild type and mutations on CCA. RNA sequencing was to investigate the changes in alternative splicing events in the mutation group compared to the wild-type group. Minigene splicing reporter and interaction assays were performed to elucidate the mechanism of mutation influence on alternative splicing events. RESULTS: RBM10 mutations were more common in Chinese CCA populations and exhibited more protein truncation variants. RBM10 exerted a tumor suppressive effect in CCA and correlated with favorable prognosis of CCA patients. The overexpression of wild-type RBM10 enhanced the ASPM exon18 exon skipping event interacting with SRSF2. The C761Y mutation in the C2H2-type zinc finger domain impaired its interaction with SRSF2, resulting in a loss-of-function mutation. Elevated ASPM203 stabilized DVL2 and enhanced ß-catenin signaling, which promoted CCA progression. CONCLUSIONS: Our results showed that RBM10C761Y-modulated ASPM203 promoted CCA progression in a Wnt/ß-catenin signaling-dependent manner. This study may enhance the understanding of the regulatory mechanisms that link mutation-altering splicing variants to CCA.

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

An Immunohistochemical Analysis of Osteopontin and S100 Calcium-binding Protein P is Useful for Subclassifying Large- and Small-duct Type Intrahepatic Cholangiocarcinomas.

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.

[A Case of Hilar Cholangiocarcinoma Arising during Long-Term Follow-Up of Hepatolithiasis].

A 91-year-old man had a history of cholecystectomy and choledochostomy for cholecystolithiasis and choledocholithiasis. Eleven years earlier, intrahepatic stones were found in the posterior bile duct, and he did not wish to undergo treatment. Over time, worsening of the intrahepatic stones and dilation of the intrahepatic bile duct were observed. At 91 years old, enhanced abdominal CT revealed wall thickening of the hilar bile duct, and MRCP showed stenosis of the hilar bile duct. Endoscopic retrograde cholangiography showed no contrast in the right intrahepatic bile duct and marked dilation of the left intrahepatic bile duct. Brush cytology confirmed adenocarcinoma, leading to a diagnosis of hilar cholangiocarcinoma. He underwent open right and caudal lobectomy with biliary reconstruction. Histopathological examination revealed a hilar cholangiocarcinoma, T3N1M0, Stage Ⅲc, mainly located at the confluence of the right and left hepatic ducts. This case suggests a potential association between hepatolithiasis and hilar cholangiocarcinoma, emphasizing the importance of regular imaging examinations for timely surgical resection. Early intervention, including liver resection, is recommended for the management of hepatolithiasis.

Caroli's disease misdiagnosed as bile duct cystadenoma: A case report.

Caroli's disease is also known as Congenital intrahepatic bile duct dilatation, and previously known as a congenital intrahepatic bile duct cyst; it is characterized by single or multiple intrahepatic cystic dilatations. In this article, we report a case of Caroli's disease (CT size 21.2 × 16.9 × 19.8 cm). Preoperative abdominal ultrasound and enhanced CT were misdiagnosed as biliary cystadenoma or hepatic echinococcosis, and finally diagnosed as Caroli's disease by postoperative histopathological examinations. Most of the disease is single or multiple cystic dilatation of small bile duct. Giant Caroli disease, cystic dilations with diameter >20 cm is very rarely seen in the clinic. The lack of experience of diagnosing giant cystic dilatation makes it difficult to make accurate diagnosis. Therefore, we analyze the causes of imaging misdiagnosis through this case report, and summarize the imaging diagnostic skills of the disease combined with relevant imaging diagnosis experience. The purpose of this study is to deepen the understanding of giant Caroli disease among imaging doctors so as to reduce the misdiagnosis of the disease in the future.

Anti-PD-1 antibody in combination with radiotherapy as first-line therapy for unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis despite treatment with standard combination chemotherapy. We aimed to evaluate the efficacy and safety of radiotherapy in combination with an anti-PD-1 antibody in unresectable iCCA without distant metastases. METHODS: In this phase II study, patients with histopathologically confirmed unresectable primary or postoperative recurrent iCCA without distant metastases were enrolled. Patients received external radiotherapy with a dose of ≥45 Gy (2-2.5 Gy per fraction), followed by anti-PD-1 immunotherapy (camrelizumab 200 mg once, every 3 weeks) initiated within 7 days after completion of radiotherapy as first-line therapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The secondary end points included safety, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: From December 2019 to March 2021, 36 patients completed radiotherapy and at least one cycle of immunotherapy and were included in efficacy and safety analyses. The median follow-up was 19.0 months (IQR 12.0-24.0), and the one-year PFS rate was 44.4% (95% CI, 30.8-64.0). The median PFS was 12.0 months (95% CI, 7.5-not estimable); the median OS was 22.0 months (95% CI, 15.0-not estimable). The ORR was 61.1% and the DCR was 86.1%. Seventeen of 36 (47.2%) patients experienced treatment-related adverse effects (AEs) of any grade. The most common AE was reactive cutaneous capillary endothelial proliferation (25.0%). Five (13.9%) patients experienced grade ≥3 treatment-related AEs, including decreased lymphocyte (5.6%), bullous dermatitis (2.8%), decreased platelet count (2.8%), and deep-vein thrombosis (2.8%). CONCLUSIONS: External radiotherapy plus camrelizumab, as first-line therapy, met its primary endpoint and showed antitumor activity and low toxicity levels in patients with unresectable iCCA without distant metastases, warranting further investigation. TRIAL REGISTRATION: NCT03898895. Registered 2 April 2019.

Interpretable machine learning-based clinical prediction model for predicting lymph node metastasis in patients with intrahepatic cholangiocarcinoma.

OBJECTIVE: Prediction of lymph node metastasis (LNM) for intrahepatic cholangiocarcinoma (ICC) is critical for the treatment regimen and prognosis. We aim to develop and validate machine learning (ML)-based predictive models for LNM in patients with ICC. METHODS: A total of 345 patients with clinicopathological characteristics confirmed ICC from Jan 2007 to Jan 2019 were enrolled. The predictors of LNM were identified by the least absolute shrinkage and selection operator (LASSO) and logistic analysis. The selected variables were used for developing prediction models for LNM by six ML algorithms, including Logistic regression (LR), Gradient boosting machine (GBM), Extreme gradient boosting (XGB), Random Forest (RF), Decision tree (DT), Multilayer perceptron (MLP). We applied 10-fold cross validation as internal validation and calculated the average of the areas under the receiver operating characteristic (ROC) curve to measure the performance of all models. A feature selection approach was applied to identify importance of predictors in each model. The heat map was used to investigate the correlation of features. Finally, we established a web calculator using the best-performing model. RESULTS: In multivariate logistic regression analysis, factors including alcoholic liver disease (ALD), smoking, boundary, diameter, and white blood cell (WBC) were identified as independent predictors for LNM in patients with ICC. In internal validation, the average values of AUC of six models ranged from 0.820 to 0.908. The XGB model was identified as the best model, the average AUC was 0.908. Finally, we established a web calculator by XGB model, which was useful for clinicians to calculate the likelihood of LNM. CONCLUSION: The proposed ML-based predicted models had a good performance to predict LNM of patients with ICC. XGB performed best. A web calculator based on the ML algorithm showed promise in assisting clinicians to predict LNM and developed individualized medical plans.

Cholangiocarcinoma: Epidemiology and Imaging-Based Review.

Cholangiocarcinoma (CCA) is a rare cancer of the bile duct epithelium, and in the last few decades its incidence rate has been increasing. It is associated with a high mortality rate due to late diagnosis and its aggressive nature. Many risk factors have been identified; some are more common in certain regions than others. CCA can be classified according to its anatomical location or macroscopic growth pattern, the latter being most helpful for imaging interpretation. Clinical features can vary from obstructive-like symptoms to nonspecific symptoms, such as weight loss and malaise. Imaging, specifically MRI/MRCP, is crucial in diagnosing CCA, staging, and treatment planning. Surgery with chemotherapy is the mainstay treatment option, and other palliative treatment options exist for those who have unresectable disease.