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Disseminated carcinomatosis of the bone marrow (DCBM) is often accompanied by disseminated intravascular coagulation (DIC) and has a poor prognosis. DCBM develops most frequently in gastric cancer and is rarely associated with intrahepatic cholangiocarcinoma. A 41-year-old man was incidentally found to have DIC on his regular visit for ulcerative colitis and was diagnosed with DCBM with intrahepatic cholangiocarcinoma. He received intensive care, including chemotherapy, but died suddenly from hyperkalemia, possibly due to tumor lysis syndrome (TLS). The autopsy showed the periductal infiltrating type of intrahepatic cholangiocarcinoma and tumor necrosis, possibly due to chemotherapy, indicating the effectiveness of chemotherapy for DCBM with intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.

Cholangiocarcinoma (CCA) represents the second most common primary liver malignancy after hepatocellular carcinoma and has risen in incidence globally in the past decades. Intrahepatic cholangiocarcinoma (iCCA) comprises 20% of all CCAs, with the rest being extrahepatic (including perihilar [pCCA] and distal CCA). Though long representing an absolute contraindication for liver transplantation (LT), recent analyses of outcomes of LT for iCCA have suggested that iCCA may be a potentially feasible option for highly selected patients. This has been motivated both by successes seen in outcomes of LT for other malignancies such as HCC and perihilar CCA and by several retrospective reviews demonstrating favorable results with LT for a selected group of iCCA patients with small lesions. LT for iCCA is primarily relevant within two clinical scenarios. The first includes patients with very early disease (single tumor ≤2 cm) with cirrhosis and are not candidates for liver resection (LR). The second scenario is patients with locally advanced iCCA, but where the extent of LR would be too extensive to be feasible. Preliminary single-center reports have described LT in a selected group of patients with locally advanced tumors which have responded to neoadjuvant therapy and have a period of disease stability. Currently, there are three prospective trials underway that will help clarify the role of LT in iCCA. This review seeks to explore the available studies involving LT for iCCA, the challenges of ongoing trials, and opportunities for the future.

Objective: The aim of this study was to explore the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC). Methods: Clinical and pathological data were collected from 147 ICC patients who attended two tertiary centers over the past 5 years. The patients were classified into two groups: the LND group (group A) and the no-performance LND (NLND) group (group B). Clinical and pathological parameters were compared between the two groups to analyze the impact of LND on the long-term survival time of ICC patients. Results: Of the 147 patients, 54.4% (80) received LND and 42.5% (34/80) of these were found to have lymph node metastasis (LNM). LND did not increase postoperative complications (27.5%, P = 0.354), but postoperative hospital stays were longer (12.2 ± 6.3 d, P = 0.005) in group A compared with group B (20.9%, 9.5 ± 3.5 d). The 5-year survival rates of groups A and B are almost similar (21% vs 29%, P = 0.905). The overall survival rate of cN0 (diagnosis obtained by imaging) is better than pN1 (diagnosis obtained by histopathology), but lower than pN0 (all P

Background: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent liver cancer. The overall survival of iCCA and other biliary tract cancers (BTC) remains poor. Recently, the ABC-06 trial reported the superiority of FOLFOX vs clinical observation as a second-line treatment. Still, the survival benefit was less than expected. We hypothesized that the pattern of progression of iCCA can drive post-progression survival (PPS), similar to hepatocellular carcinoma. Methods: Multicentre retrospective evaluation of consecutive iCCA patients who progressed after frontline systemic treatment with gemcitabine as monotherapy or in combination with platinum. Radiological assessment of progression was evaluated according to RECIST 1.1. The progression pattern was divided according to the presence/absence of new extrahepatic lesions (NEH). Results: We included 206 patients from 5 centres. The median OS was 14.1months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were previous surgery 0.699 [0.509-0.961], performance status >2.445 [1.788-3.344], permanent first-line discontinuation 16.072 [5.102-50.633], registration of ascites 2.226 [1.448-3.420] or bilirubin >3mg/dl 3.004 [1.935-4.664] during the follow-up, and disease progression 2.523 [1.261-5.050]. The appearance of NEH independently predicted OS 2.18 [1.55-3.06] in patients with radiological progression. Amongst 138 patients eligible for second-line treatment, PPS was 16.8 and 5.9months in cases without and with NEH, respectively (P=.001). Progression owing to NEH lesions was an independent predictor of PPS 1.873 [1.333-2.662], together with performance status, time to progression to the frontline treatment, bilirubin >3mg/dl and ascites. Conclusions: PPS of iCCA is influenced by progression pattern, with important implications for second-line trial design and analysis.

BACKGROUND: Accurate diagnosis of intrahepatic cholangiocarcinoma (ICC) caused by intrahepatic lithiasis (IHL) is crucial for timely and effective surgical intervention. The aim of the present study was to develop a nomogram to identify ICC associated with IHL (IHL-ICC). METHODS: The study included 2,269 patients with IHL, who received pathological diagnosis after hepatectomy or diagnostic biopsy. Machine learning algorithms including Lasso regression and random forest were used to identify important features out of the available features. Univariate and multivariate logistic regression analyses were used to reconfirm the features and develop the nomogram. The nomogram was externally validated in two independent cohorts. RESULTS: The seven potential predictors were revealed for IHL-ICC, including age, abdominal pain, vomiting, comprehensive radiological diagnosis, alkaline phosphatase (ALK), carcinoembryonic antigen (CEA), and cancer antigen (CA) 19-9. The optimal cutoff value was 2.05 µg/L for serum CEA and 133.65 U/mL for serum CA 19-9. The accuracy of the nomogram in predicting ICC was 82.6%. The area under the curve (AUC) of nomogram in training cohort was 0.867. The AUC for the validation set was 0.881 from The Second Affiliated Hospital of Wenzhou Medical University, and 0.938 from The First Affiliated Hospital of Fujian Medical University. CONCLUSIONS: The nomogram holds promise as a novel and accurate tool to predict IHL-ICC, which can identify lesions in IHL in time for hepatectomy or avoid unnecessary surgical resection.

Large hepatic tumors can invade the retrohepatic inferior vena cava (IVC). Resecting the involved IVC wall is necessary to achieve complete tumor resection. We present detailed surgical procedures of IVC resection and patch venoplasty under the standard and modified total hepatic vascular exclusion (THVE) techniques applied to two patients who underwent aggressive surgery for hepatic tumors. The first case was a 55-year-old male with advanced intrahepatic cholangiocarcinoma. The extent of resection was extended right hepatectomy with caudate lobe resection, right adrenalectomy, and portal vein segmental resection-anastomosis. The invasion site at the IVC was excised and repaired with an expanded polytetrafluoroethylene patch under modified THVE. This patient recovered uneventfully. At postoperative 10 months, second primary cancer occurred in the duodenum. The patient underwent pancreaticoduodenectomy but passed away at post-surgery 6 weeks due to pneumonia-associated sepsis. The second case was a 35-year-old female with giant cavernous hemangioma. As separating the right liver from the IVC was infeasible through conventional dissection techniques, standard THVE was performed. The short hepatic vein was too large to repair directly without risk of IVC stenosis. Thus, a cryopreserve iliac vein allograft patch was applied to repair the defect. The patient recovered uneventfully from the operation. The patient is currently doing well for 6 years. However, progressive hemangiomatosis occurred. In conclusion, standard and modified THVE techniques are proposed as useful techniques to achieve complete tumor resection in patients with large liver tumors invading the retrohepatic IVC.

OBJECTIVES This study valued MR delayed enhancement pattern in predicting postoperative prognosis of intrahepatic mass-forming cholangiocarcinoma (IMCC). METHODS From 2011 to 2015, 231 patients of IMCC underwent DCE-MRI preoperatively. Enhancement patterns and MRI characteristics were evaluated. Recurrence and mortality data were compared among IMCCs with different enhancement patterns. Prognostic factor analysis was performed using preoperative and postoperative clinical-pathologic factors, as well as imaging findings. RESULTS Fifty-six (24.2%), 142 (61.5%) and 33 (14.3%) tumors showed hypo, peripheral rim and diffuse hyper enhancement in AP. Fifty-six (24.2%), 81 (35.1%) and 94 (40.7%) tumors showed hypo, heterogeneous and uniform enhancement in DP. Patients with arterial diffuse hyper enhancement or delayed uniform enhancement IMCCs had lower preoperative CA19-9 levels, smaller tumor sizes and minor operations than the rest patients (p

Background/aims Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated. Methods Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancer-related genes. Results From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR and PTPRT were most frequently mutated (three cases each) including an FGFR-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found. Conclusions iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR and ARID1A variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.

Intrahepatic cholangiocarcinoma (ICC) is one of the rarest and most aggressive types of cancer. The symptoms of ICC patients can be vague, leading to late diagnosis and dismal prognosis. In this review, we investigated the treatment options for ICC, as well as ways to overcome challenges in identifying and treating this disease. Imaging remains the gold standard to diagnose ICC. Patients are staged based on the tumor, nodes and metastases (TNM) staging system. Patients eligible for surgical resection should undergo surgery with curative intent with the goal of microscopically disease-free margins (R0 resection) along with lymphadenectomy. Minimal invasive surgery (MIS) and liver transplantation have recently been offered as possible ways to improve disease outcomes. ICC recurrence is relatively common and, thus, most patients will need to be treated with systemic therapy. Several clinical trials have recently investigated the use of neoadjuvant (NT) and adjuvant therapies for ICC. NT may offer an opportunity to downsize larger tumors and provide patients, initially ineligible for surgery, with an opportunity for resection. NT may also treat occult micro-metastatic disease, as well as define tumor biology prior to surgical resection, thereby decreasing the risk for early postoperative recurrence. Adjuvant systemic therapy may improve outcomes of patients with ICC following surgery. Ongoing clinical trials are investigating new targeted therapies that hold the hope of improving long-term outcomes of patients with ICC.

To evaluate the efficacy of percutaneous biopsy for diagnosing intrahepatic cholangiocarcinoma (IHCCA). Retrospective review of biopsy and pathology databases from 2006 to 2019 yielded 112 patients (54F/58 M; mean age, 62.9 years; 27 cirrhotic) with IHCCA who underwent percutaneous biopsy. Data regarding the lesion, biopsy procedure technique, and diagnostic yield were collected. If biopsy was non-diagnostic or discordant with imaging, details of repeat biopsy or resection/explant were gathered. A control group of 100 consecutive patients (56F/44 M; mean age, 63 years, 5 cirrhotic) with focal liver lesions > 1 cm was similarly assessed. Mean IHCCA lesion size was 6.1 ± 3.6 cm, with dominant lesion sampled in 78% (vs. satellite in 22%). 95% (n = 106) were US guided and 96% were core biopsies (n = 108), typically 18G (n = 102, 91%), median 2 passes. 18 patients (16%) had discordant/ambiguous pathology results requiring repeat biopsy, with two patients requiring 3–4 total attempts. A 4.4% minor complication rate was seen. Mean time from initial biopsy to final diagnosis was 60 ± 120 days. Control group had mean lesion size of 2.9 ± 2.5 cm and showed a non-diagnostic rate of 3.3%, both significantly lower than that seen with CCA, with average time to diagnosis of 21 ± 28.8 days (p = 0.002, p = 0.001). IHCCA is associated with lower diagnostic yield at initial percutaneous biopsy, despite larger target lesion size. If a suspicious lesion yields a biopsy result discordant with imaging, the radiologist should recommend prompt repeat biopsy to prevent delay in diagnosis.

The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. High invasion and metastasis are one of the main causes of death in patients. The selection of reasonable and effective molecular markers to evaluate the prognosis of patients with ICC has important clinical guiding significance. In this study, the expression of Tspan protein in ICC and normal tissues was compared, the correlation between Tspan expression and pathological features of patients was analyzed by the logistic regression model using multivariate analysis, and the relationship between Tspan8 expression and prognosis of ICC patients was analyzed by the Kaplan–Meier survival curve. The results showed that Tspan8 is highly positive in ICC tissues, TNM stage, degree of tumor differentiation, lymph node metastasis, and Tspan8 protein expression were independently correlated, and the overexpression of Tspan was associated with the prognosis of ICC invasion and metastasis. This provides a new idea for clinical treatment.

BACKGROUND The duration of surveillance after curative resection of colorectal cancer (CRC) is generally 5 years. The overall incidence of recurrence more than 5 years after surgery for CRC in Japan has been reported to be 0.6%. Moreover, it is rare for CRC to have metachronous liver metastasis more than 10 years after surgery. Here, we present a case of liver metastasis detected 11 years after the curative resection of rectal cancer. CASE SUMMARY A 72-year-old man was referred to our hospital after a liver tumor was detected by abdominal ultrasonography at another hospital. He had undergone surgery for rectal cancer 11 years previously. Contrast-enhanced computed tomography (CT) showed a tumor with a diameter of approximately 8 cm in the posterior segment, which was weakly and gradually enhanced. 18F-fluorodeoxyglucose-positron emission tomography/CT showed an abnormally high uptake on the tumorous lesion, which showed that the tumor appeared to spread convexly along the intrahepatic bile ducts. Intrahepatic cholangiocarcinoma was therefore diagnosed, and he had an extended right posterior sectionectomy and regional lymph node dissection. Histopathological examination showed that the tumor was a moderately differentiated adenocarcinoma and showed the same pathological characteristics as the rectal cancer. Immunohistological examination showed that the cancer cells of both the liver tumor and rectal cancer were positive for cytokeratin (CK) 20 and weakly positive for CK 7. These findings were consistent with the liver metastasis from the rectal cancer. CONCLUSION It is possible that a liver tumor is metastatic in a patient with a previous history of CRC, even if it was more than 10 years earlier.

Background We compared the outcomes of laparoscopic hepatectomy (LH) vs. open hepatectomy (OH) for intrahepatic cholangiocarcinoma (iCCA). Methods A systematic review of the MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed using PRISMA guidelines (end-of-search date: 08-June-2020). Individual patient data on overall survival (OS) and recurrence-free survival (RFS) were extracted. Random-effects meta-analyses, and one- and two-stage survival analyses were conducted. Results Eight retrospective cohort studies comparing LH (n = 544) vs. OH (n = 2256) were identified. LH demonstrated lower overall complication (Risk ratio [RR] = 0.64, 95% confidence interval [CI]: 0.46–0.90; p = 0.01), surgical lymphadenectomy (RR = 0.74, 95% CI: 0.58–0.93; p = 0.01) and margin-positive resection (RR = 0.78, 95% CI: 0.62–0.99; p = 0.04) rates, and higher recurrence-free rate (RR = 1.24, 95% CI: 1.01–1.51; p = 0.04) vs. OH. In Cox regression, no difference was observed regarding OS (Hazard Ratio [HR] = 1.11, 95% CI: 0.65–1.91; p = 0.70) and RFS (HR = 1.19, 95% CI: 0.74–1.90; p = 0.47). Conclusion The use of LH should be considered when feasible in well-selected iCCA patients by hepatobiliary surgeons with experience in minimally-invasive surgery.

Summary Inhibin-positive hepatic carcinoma is a rare primary liver neoplasm that resembles sex cord–stromal tumor and thyroid follicular tumors. The term “cholangioblastic variant of intrahepatic cholangiocarcinoma” has been proposed. This study describes the clinicopathologic, immunophenotypic, and molecular features of a small series (n = 6) of this rare tumor. Albumin in situ hybridization (ISH) and capture-based next-generation sequencing (NGS) were also performed. All tumors occurred in young women (mean age 32.5 years, range 19–44 years) as a solitary large mass (mean 15.8 cm, range 6.9–23.5 cm). All tumors showed a highly distinctive morphology with sheets and large nests of tumor cells alternating with tubular and cystic areas imparting a sex cord–like or thyroid follicle–like morphology. Cytologic atypia was mild, and mitotic activity was low. All cases were positive for inhibin, as well as pancytokeratin, CK7, CK19, and albumin ISH. Synaptophysin and chromogranin showed focal or patchy staining, whereas INSM1 was negative. Markers for hepatocellular differentiation, thyroid origin, and sex cord–stromal tumor were negative. There were no recurrent genomic changes based on capture-based NGS of ∼500 cancer genes. Recurrence and/or metastasis was seen in three (50%) cases (follow-up time range for all cases: 5 months to 2 years). In conclusion, this series describes the distinctive morphology, immunophenotypic features, and diffuse albumin staining in six cases of a rare inhibin-positive primary liver carcinoma that runs an aggressive course similar to intrahepatic cholangiocarcinoma. Genomic changes typical of cholangiocarcinoma or hepatocellular carcinoma were not identified, and there were no recurrent genetic abnormalities. We propose the term “solid-tubulocystic variant of intrahepatic cholangiocarcinoma” to reflect the spectrum of morphologic patterns observed in this tumor.

Background While a certain degree of tumor infiltration of the portal vein is common in patients with perihilar cholangiocarcinoma (pCCA) scheduled for surgery, complete tumor-associated portal vein occlusion (PVO) is less frequently observed. Here, we analyzed the impact of PVO on perioperative and oncological outcomes in pCCA patients. Methods Between 2010 and 2019, 127 patients with pCCA underwent surgery in curative intent at our department of which 17.3% (22/127) presented with PVO. Extensive group comparisons were conducted and the association of cancer-specific (CSS) and disease-free survival (DFS) with PVO and other clinico-pathological characteristics were assessed using Cox regression models. Results Patients without PVO showed a median CSS of 65 months (3-year-CSS = 64%, 5-year-CSS = 53%) compared to 31 months (3-year-CSS = 43%, 5-year-CSS = 17%) in patients with PVO (p = 0.025 log rank). Patients with PVO did also display significant perioperative mortality (22.7%, 5/22) compared to patients without PVO (14.3%, 15/105, p = 0.323). Further, PVO (CSS: HR = 5.25, p = 0.001; DFS: HR = 5.53, p = 0.001) was identified as independent predictors of oncological outcome. Conclusions PVO has been identified as an important prognostic marker playing a role in inferior oncological outcome in patients with pCCA. As PVO is also associated with notable perioperative mortality, surgical therapy should be considered carefully in pCCA patients.

Background The aim of this study was to investigate the prognostic value of arginase-1 (Arg-1) and glypican-3 (GPC-3) in patients with intrahepatic cholangiocarcinoma (ICC). Methods Two hundred and thirty-seven patients with ICC were included in this study. All patients had undergone radical surgery and had complete clinical information. Immunohistochemistry was used to assess the levels of Arg-1 and GPC-3 in ICC tissues. Univariate and multivariate analyses were conducted to identify independent risk factors in ICC. The relationship between Arg-1 and GPC-3 levels and patient survival was determined using the Kaplan-Meier method. Results High Arg-1 and GPC-3 expression levels were associated with poor prognosis in patients with ICC, and they could be as new prognostic biomarkers in ICC. Conclusion Arg-1 and GPC-3 can serve as independent prognostic biomarkers in ICC.

Tumor-infiltrating lymphocytes (TILs) are a prognostic factor or an indicator of chemotherapy response for various malignancies. The aim of this study was to investigate the prognostic impact of TILs in resected intrahepatic cholangiocarcinoma (IHCC). We also investigated the usefulness of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) to predict TILs. We enrolled 23 patients with IHCC who underwent initial hepatic resection in Tokushima University Hospital from 2006 to 2017. We evaluated stromal TILs in the tumor marginal area and central area in surgical specimens. Patients were divided into low vs high stromal TILs groups. We analyzed the patients’ clinicopathological factors, including prognosis, according to the degree of stromal TILs. We also analyzed the correlation between stromal TILs and the minimum ADC value. Stromal TILs in the marginal area reflected overall survival more accurately than that in the central area. Additionally, marginal low TILs was significantly associated with lymph node metastasis and portal vein invasion. Both overall- and disease-free survival rates in the marginal low TILs group were significantly worse than those in the marginal high TILs group (P

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. Chemotherapy remains the main therapeutic strategy for advanced ICC patients, but chemosensitivity varies individually. Here, we applied cytometry by time-of-flight (CyTOF) to establish the immune profile of peripheral blood mononuclear cells (PBMCs) on the single-cell level at indicated time points before, during, and after chemotherapy. Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters. Tissue microarrays (TMAs) were used for prognostic evaluation. A total of 20 ICC patients treated with gemcitabine (GEM) were enrolled in our study, including eight cases with good response (R) and 12 cases with non-response (NR). Tremendous changes in PBMC composition, including an increased level of CD4/CD8 double-positive T cells (DPT), were observed after chemotherapy. Patients with higher level of CD4+CD45RO+CXCR3+ T cells before treatment had a favorable response to chemotherapy. Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy, which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.

Background Intrahepatic cholangiocarcinoma (iCCA) is a contraindication to liver transplantation in most centers worldwide. Therefore, only a few such cases have been performed in each individual center, and the need for a systematic review and meta-analysis to cumulatively pool these results is apparent. Methods A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (end-of-search date: May 29, 2020). Meta-analyses of proportions were conducted to pool the overall survival (OS), recurrence-free survival (RFS), and overall recurrence rates using the random-effects model. Meta-regression was used to examine cirrhosis and incidental diagnosis as confounders on OS and RFS. Results Eighteen studies comprising 355 patients and a registry study of 385 patients were included. The pooled 1-, 3-, and 5-y OS rates were 75% (95% CI, 64%-84%), 56% (95% CI, 46%-67%), and 42% (95% CI, 29%-55%), respectively. The pooled 1-, 3-, and 5-y RFS rates were 70% (95% CI, 63%-75%), 49% (95% CI, 41%-57%), and 38% (95% CI, 27%-50%), respectively. Cirrhosis was positively associated with RFS, while incidental diagnosis was not. Neither cirrhosis nor incidental diagnosis was associated with OS. The pooled overall recurrence rate was 43% (95% CI, 33%-53%) over a mean follow-up of 40.6 ± 37.7 mo. Patients with very early (single ≤2 cm) iCCA exhibited superior pooled 5-y RFS (67%; 95% CI, 47%-86%) versus advanced iCCA (34%; 95% CI, 23%-46%). Conclusions Cirrhotics with very early iCCA or carefully selected patients with advanced iCCA after neoadjuvant therapy may benefit from liver transplantation under research protocols.

Background Bile duct adenomas (BDA) may be precursor lesions of small duct-type, including mass-forming type intrahepatic cholangiocarcinoma (ICC). Case report A 68-year-old woman was transferred to our facility for the treatment of a liver tumor, possibly metastasized from a pancreatic neuroendocrine tumor. Finally, two liver tumors were resected and histopathologically diagnosed as "BDA" and "ICC with a BDA-like component". In the BDA-like component, the MUC6 positive rate was notably lower and the Ki-67 positive rate was higher than the other BDAs and ICC component, respectively. The doubling time of the tumor volume in BDA was very long but was shortened (1,510 and 719 days). Distinct enlargement of the tumor and appearance of enhancement through diagnostic imaging was useful in diagnosing the transformation from a BDA to an ICC. Conclusion An "adenoma-carcinoma sequence" may exist in the transformation process from a BDA to an ICC.

Purpose To investigate safety, response, and survival after ablative glass microsphere 90Y radioembolization for unresectable intrahepatic cholangiocarcinoma. Materials and methods A retrospective review of 37 radioembolizations in 28 patients treated with single compartment dose of ≥190 Gy encompassing >75% of the largest tumor was performed. Tumors were assessed for stage, morphology, and arterial supply. Response per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), freedom from progression (FFP), progression-free survival (PFS), overall survival (OS), biochemical hepatic function, performance status, and adverse events were investigated. Results The median highest dose per patient was 256.8 Gy (195.7-807.8). Objective response at 3 months was 94.1% (complete 44.1% and partial 50%). Median OS was not reached and the 30-month OS rate was 59%, with a median follow-up of 13.4 months (5.4-39.4). FFP in the radiated field and overall FFP at 30 months were 67% and 40%, respectively. Favorable arterial supply was associated with improved OS (p = 0.018). Unfavorable arterial supply was associated with worse OS [HR 5.7 (95% CI 1.1-28.9, p = 0.034)], and PFS [HR 5.9 (95% CI 1.9-18.4, p = 0.002)]. Patients with mass-forming tumors had a survival benefit (p = 0.002). Laboratory values and performance status did not significantly change 3 months after radioembolization. Grade 3 and 4 adverse events occurred in 2 (7.1%) patients. Conclusions Radioembolization of unresectable intrahepatic cholangiocarcinoma with ablative intent has a high response rate, promising survival, and is well tolerated.

Different histopathological manifestations of focal liver lesions show varying common and uncommon imaging findings and some pathologies may show similar appearance despite of different histopathology. It is necessary to characterise focal liver lesions accurately as not only benign and malignant lesions are managed differently, but also certain benign lesions have differing management. These lesions are increasingly being detected due to rapid growth of use of cross-sectional imaging as well as improvement in image quality and new imaging techniques. Contrast enhanced magnetic resonance imaging (MRI) is considered the gold standard technique in characterising focal liver lesions. Addition of gadoxetic acid has been shown to significantly increase diagnostic accuracy in the detection and characterization of liver abnormalities. Classic imaging characteristics of common liver lesions, including their behaviour on gadoxetic acid enhanced MRI, have been described in literature over recent years. It is important to be familiar with the typical aspects of these lesions as well as know the uncommon and overlapping imaging features to reach an accurate diagnosis. In this article, we will review the well-described characteristic imaging findings of common and rare focal liver lesions and present several challenging cases encountered in the clinical setting, namely hepatocellular adenoma, focal nodular hyperplasia, hepatic angiomyolipoma, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours as well as a pleomorphic liposarcoma of the liver.

Cholangiocarcinoma (CCA) is a primary malignancy of the bile ducts with three anatomically and molecularly distinct entities: Intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA. As a result of phenotypic and anatomic differences they differ significantly with respect to management. For each type of CCA there have been significant changes in management over the last several years which will be discussed in this review. Although resection remains the standard of care for all types of CCA, liver transplantation has been established as curative treatment for selected patients with pCCA and is being evaluated for iCCA with early success. With respect to systemic therapy capecitabine is now first line adjuvant therapy for all biliary tract malignancies after curative intent resection. Progress in exploiting the pathologic mutations and molecular abnormalities has also yielded regulatory approval of targeted therapy for CCA in patients with acquired alterations in the fibroblast growth factor receptor. There is also increased consensus in managing malignant biliary obstruction associated with CCA where pre-operative biliary stenting is not beneficial while self-expanding metal stents have been shown to be superior to plastic stents in patients who are not surgical candidates.

BACKGROUND AND AIMS Intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) are the most common primary liver cancers (PLCs). Differences in their clinical features and outcomes are open for investigation in a large-scale study. We aim to investigate the differences in clinical features and outcomes between iCCA and HCC. APPROACH AND RESULTS The Surveillance, Epidemiology, and End Results Program 18 Database (2000-2017) was used to extract demographic and clinical features of HCC and iCCA patients. Logistic regression analysis was performed to identify factors associated with iCCA diagnosis versus HCC. Cox regression analysis was used to assess factors affecting overall survival (OS). There were 13,611 iCCA and 96,151 HCC patients. Half of iCCA (50.7%) and three quarters of HCC (76.3%) patients were male. Diagnosis in recent year, age (

Background Hepatectomy is the only potentially curable treatment for intrahepatic cholangiocarcinoma (IHCC) and colorectal liver metastasis (CRLM). This study aimed to explore the difference in intraoperative outcomes and postoperative complications between IHCC and CRLM in different surgical methods including major hepatectomy and minor hepatectomy. Methods We included 319 patients with IHCC or CRLM who underwent hepatectomy at our hospital. According to major hepatectomy and minor hepatectomy, eligible patients were divided into two groups. In each group, the clinicopathological characteristics of IHCC and CRLM patients were compared, then propensity score matching (PSM) was performed based on the results. Intraoperative outcomes and postoperative complications were compared between IHCC and CRLM before and after PSM. Intraoperative variables, including intraoperative blood transfusion, duration of operation, and intraoperative blood loss, were used to evaluate the intraoperative conditions of patients. The postoperative complications were measured according to the Clavien-Dindo classification. Grade III to V complications were defined as major complications. Results The major hepatectomy group included 118 patients with IHCC and 93 patients with CRLM. IHCC patients presented a longer operation time and a higher postoperative complication rate than CRLM patients. The infection-related complication rate of the CRLM patients was significantly higher than the IHCC patients. In multivariate analysis, major hepatectomy for IHCC was independently associated with the presence of postoperative complications. The minor hepatectomy group included 146 IHCC patients and 62 CRLM patients. Compared with CRLM patients, IHCC patients presented a longer operation time. There was no significant difference in the intra-operative blood loss, postoperative complication rate, the major complications rate, and the minor complications rate between the IHCC patients and CRLM patients. Conclusions This study revealed major hepatectomy for IHCC led to significantly higher morbidity of postoperative complications than CRLM patients. For minor hepatectomy, there was no difference in postoperative complications between IHCC and CRLM. More attention should be paid to improving the preoperative planning and surgical management of hepatic malignancies especially in the setting of IHCC.

Maffucci syndrome is characterized by multiple hemangiomas and enchondromas. Somatic mutations in IDH1 and IDH2 are associated with the development of Maffucci syndrome, and these patients develop various malignant nonskeletal tumors in addition to malignant skeletal tumors. We report a case of Maffucci syndrome with IDH1 mutation complicated by intrahepatic cholangiocarcinoma. The patient was a 35-year-old woman who was diagnosed with Maffucci syndrome in childhood. She was referred to our department because of a large hepatic tumor. Serum carcinoembryonic antigen was 27.1 ng/mL upon laboratory examination. CT scanning showed a large low-density tumor (90 × 70 mm) in the right lobe of the liver, and MRI revealed a multilobulated and fibrous tumor, which was observed as high signal intensity on T2- and diffusion-weighted images and low signal intensity on T1-weighted images. Positron emission tomography-CT revealed peritoneal dissemination and cancer spread to the muscles of the back. Finally, she was diagnosed with intrahepatic cholangiocarcinoma with dissemination and metastases. We performed a tumor biopsy to determine a treatment plan for chemotherapy. Sanger sequencing of a tumor biopsy identified a mutation in IDH1 at c.394C>T (R132C), but the patient died of rapid cancer progression before the chemotherapy could be initiated. Although rare, malignant tumors can develop in patients with Maffucci syndrome; therefore, it is necessary to monitor these tumors through careful and periodic observation.

Background: To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system. Methods: Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n = 643). An external validation dataset was obtained from the SEER registry (n = 797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1-2 LNM) and N2 (≥3 LNM). Results: The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p < 0.05), and SEER (Median OS, stage I 87.0 vs. II 29.3 vs. III 17.7 vs. IV 14.2 months, all p < 0.05) datasets, which was also verified among patients who had ≥6 lymph node harvested from both databases. Conclusion: The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging. info:eu-repo/semantics/publishedVersion

This study aimed to investigate the impact of surgery on outcomes in patients with recurrent biliary tract cancer (BTC) and elucidate factors affecting survival after surgery for this disease.A single-center study was undertaken in 178 patients with recurrent BTC, of whom 24 underwent surgery for recurrence, 85 received chemotherapy, and 69 received best supportive care. Then, we carried out a multicenter study in 52 patients undergoing surgery for recurrent BTC (gallbladder cancer, 39%; distal cholangiocarcinoma, 27%; perihilar cholangiocarcinoma, 21%; intrahepatic cholangiocarcinoma, 13%).In the single-center study, 3-year survival after recurrence was 53% in patients who underwent surgery, 4% in those who received chemotherapy, and 0% in those who received best supportive care (p 0.001). Surgery was an independently prognostic factor (p 0.001). In the multicenter series, the respective 3-year and 5-year survival after surgery for recurrence was 50% and 29% in the 52 patients. Initial site of recurrence was the only independent prognostic factor (p = 0.019). Five-year survival after surgery for recurrence in patients with single distant, multifocal distant, and locoregional recurrence was 51%, 0%, and 0%, respectively (p = 0.002). Sites of single distant recurrence included the liver (n = 13, 54%), distant lymph nodes (all from gallbladder cancer, n = 7, 29%), lung (n = 2, 9%), peritoneum (n = 1, 4%), and abdominal wall (n = 1, 4%).Surgery may be an effective option for patients with less aggressive tumor biology characterized by single distant recurrence in recurrent BTC.

BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is a rare cancer. Patients in rural areas may face reduced access to advanced treatments often only available at referral centers. We evaluated the association of referral center treatment with treatment patterns, outcomes, and geography in patients with ICC. METHODS We queried the Oregon State Cancer Registry for ICC between 1997 and 2016, collecting clinicopathologic, demographic, and oncologic data. Patients were classified by treatment at a referral center or non-referral center. 'Crowfly' distance to the nearest referral center (DRC) was calculated. Outcomes were evaluated using Kaplan-Meier, Cox proportional hazards modeling, and logistic regression. RESULTS Over 20 years, 740 patients with ICC had a median age of 66 years. Slightly more than half (n = 424, 57%) were non-referral center treated and 316 (43%) were referral center treated. Referral center treatment increased over time (odds ratio [OR] 1.03/year, p

Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.

Introduction Intrahepatic cholangiocarcinoma is a primary liver neoplasm whose only curative treatment is surgery. The objective of this study was to determine the prognostic factors for survival of intrahepatic cholangiocarcinoma treated surgically with curative intent. Methods Sixty-seven patients who had been treated surgically for this neoplasm were collected at Bellvitge University Hospital between 1996 and 2017. Epidemiological, clinical, surgical, anatomopathological, morbidity, mortality and survival data have been analysed. Results Postoperative study reflects our centre’s experience in the surgical treatment of intrahepatic cholangiocarcinoma over a period of 21 years. Lymphadenectomy was associated with increased morbidity, and vascular invasion in the pathological study was the most important risk factor in the survival analysis. Conclusions This study reflects our centre's experience in the surgical treatment of intrahepatic cholangiocarcinoma over a period of 21 years. Lymphadenectomy was associated with increased morbidity, and vascular invasion in the pathological study was the most important risk factor in the survival analysis.

Haizhou Qiu, Chang Liu, Min Huang, Shu Shen, Wentao Wang Department of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaCorrespondence: Wentao WangDepartment of Liver Surgery and Liver Transplantation, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of ChinaEmail wwtdoctor02@163.comPurpose: The prognosis of intrahepatic cholangiocarcinoma (ICC) patients after surgical resection remains poor. Effective prognostic biomarkers are expected to stratify ICC patients and optimize their treatment strategies. To investigate the prognostic value of carbohydrate antigen 19-9 (CA19-9), aspartate aminotransferase to lymphocyte ratio index (ALRI), and their combination (CAC) in predicting long-term outcomes in ICC patients after hepatectomy.Patients and Methods: ICC patients underwent initial hepatectomy for curative purpose from January 2009 to September 2017 were reviewed retrospectively. Area under the receiver operating characteristics curve (AUC) was used to distinguish the identification effectiveness of three different measures. Kaplan–Meier curves and Cox proportional hazards regression were used to assess the value of preoperative CAC grade in predicting overall survival (OS) and disease-free survival (DFS).Results: A total of 530 patients were included and randomly divided into two groups (derivation cohort and validation cohort). During a median follow-up of 18 months (1– 115.4 months), 317 patients (59.8%) died and 381 patients (71.9%) developed tumor recurrence. Lower ALRI, decreased serum CA19-9 level and CAC grade were found to be associated with better OS and DFS (both P< 0.001). Importantly, the AUC for CAC grade was significantly greater than ALRI and CA19-9. In addition, results from Cox proportional hazards regression from both cohorts suggest that tumor number, node invasion, and CAC grade as independent prognostic factors for both OS and DFS.Conclusion: This study demonstrated that CAC grade is a valuable biomarker for the prognosis of ICC patients. Specifically, patients with elevated CAC grades were correlated to worse long-term outcome after the hepatectomy. Our data suggest that increased CAC grades can be used to stratify patients and help to decide their treatment strategies.Keywords: intrahepatic cholangiocarcinoma, carbohydrate antigen 19-9, aspartate aminotransferase to lymphocyte ratio, hepatectomy, prognostic predictor, long-term outcomes

Background Intrahepatic cholangiocarcinoma is an aggressive liver carcinoma with increasing incidence and mortality. A good auxiliary prognostic prediction tool is desperately needed for the development of treatment strategies. The purpose of this study was to explore the prognostic value of the radiomics nomogram based on enhanced CT in intrahepatic cholangiocarcinoma. Methods In this retrospective study, 101 patients with pathological confirmation of intrahepatic cholangiocarcinoma were recruited. A radiomics nomogram was developed by radiomics score and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by a nomogram. Model performance and clinical usefulness were assessed by calibration curve, ROC curve, and survival curve. Results A total of 101patients (mean age, 58.2 years old; range 36–79 years old) were included in the study. The 1-year, 3-year, and 5-year overall survival rates were 49.5%, 26.6%, and 14.4%, respectively, with a median survival time of 12.2 months in the whole set. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found three independent prognostic factors. The radiomics nomogram showed a significant prognosis value with overall survival. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole set (30.4% vs. 56.4% and 13.0% vs. 30.6%, respectively, p = 0.018). Conclusions This radiomics nomogram has potential application value in the preoperative prognostic prediction of intrahepatic cholangiocarcinoma and may facilitate in clinical decision-making.

BACKGROUND: Intrahepatic cholangiocarcinoma has heterogeneous outcomes after resection. There remains a need for broadly applicable recurrence-specific tool offering precise evaluation on curativeness of resection. METHODS: A four hospital-based clinical cohort involving 1,655 patients with intrahepatic cholangiocarcinoma who received surgical resection were studied. Cox and logistic models were networked into one system containing risk categories with distinctive probabilities of recurrence. Prediction of time-to-recurrence was performed by formulizing time-dependent risk probabilities. The model was validated in three clinical cohorts (n=332). RESULTS: From the training cohort, 10 and 11 covariates, including diabetes, cholelithiasis, albumin, platelet count, alpha fetoprotein, carbohydrate antigen 19-9, carcinoembryonic antigen, hepatitis B virus infection, tumor size and number, resection type, and lymph node metastasis, from Cox and logistic models were identified significant for recurrence-free survival (RFS). The combined Cox & logistic ranking system (CCLRS)-adjusted time-dependent probabilities were categorized into seven ranks (5-yr RFS for lowest and highest ranks were 75% vs. 0%; hazard ratio 18.5, 95% CI: 14.7–24.9, P

Cholangiocarcinoma is the second most common primary hepatic malignancy and is a heterogeneous tumor of biliary epithelium. We discuss the risk factors, anatomic classification of cholangiocarcinoma (CC) as well as the different morphologic subtypes of CC. Imaging findings of CC on different modalities are described, focusing on intrahepatic CC. Recently recognized imaging features that carry prognostic significance, such as a worse prognosis in tumors that have more desmoplastic stroma, are detailed. Other benign and malignant entities that should be considered in the differential diagnosis of CC will also be discussed.

Introduction Right anterior sectionectomy (RAS) is technically difficult and performed infrequently, so there were a few reports of small numbers about this surgery. We described large number of clinicopathologic and oncologic outcomes associated with RAS. Methods We retrospectively reviewed the medical records of 415 patients treated with RAS for hepatic tumors located at segment 5 and/or 8 between January 2008 and December 2017. Results All patients underwent RAS with the alternative Glissonean pedicle clamp and Kelly clamp-crushing methods for transection. The mean operative time was 165 minutes and the mean transection time was 28 minutes. Major morbidities (≥ grade III) occurred in 28 cases (6.7%). Bile leakage occurred in 63 patients (15.1%), but no patients required reoperation. Grade A/B/C post-hepatectomy liver failure occurred in 39/7/0 (9.4%/1.7%/0.0%) patients, respectively. There were no in-hospital mortality caused by postoperative complications. The mean hospital stay was 13.3 days. The most common diagnosis was hepatocellular carcinoma (HCC; n = 361, 87.0%), followed by intrahepatic cholangiocarcinoma (n = 15, 3.6%), mixed HCC and cholangiocarcinoma (n = 17, 4.1%), colorectal cancer liver metastasis (n = 12, 2.9%). The mean tumor size was 3.8 cm. Among HCC patients, the 5- and 10- year overall survival (OS) rate was 78.3%, 64.4%, and 5- and 10- year disease-free survival (DFS) rate was 57.2%, 37.7%, respectively. Operative time, tumor size, and vessel invasion were factors significantly associated with OS and DFS for HCC patients. Conclusions RAS was associated with acceptable procedure-related morbidity and mortality as well as appropriate oncologic outcomes for HCC patients.

Purpose Intrahepatic cholangiocarcinoma is the second most common primary liver cancer, and is associated with a poor prognosis and rising incidence rate. Methods Here, we reported the case of a middle-aged Asian male who presented with a 9.5-cm liver lesion and was diagnosed with intrahepatic cholangiocarcinoma. Results The patient experienced recurrence three times, twice following radical resection and standard adjuvant chemotherapy and once following camrelizumab plus apatinib, after which the tumor progressed with elevated CA 19.9 level. After tissue biopsy for next-generation sequencing, apatinib was replaced by lenvatinib, and the patient achieved disease control again, with a progression-free survival of 10 months. Conclusion Combined immunotherapy and targeted therapy regimens are a promising approach for refractory intrahepatic cholangiocarcinoma. Further well-designed prospective clinical trials are needed to confirm the efficacy and safety. Since intrahepatic cholangiocarcinoma is characterized by high heterogeneity and with complex crosstalk among oncogenic pathways, further exploration is required to more deeply understand the mechanism of action of this treatment approach and guide individualized treatment selection.

Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma that accounts for about 10%-20% of the total cases. Infection with hepatitis B virus (HBV) is one of the most important predisposing factors leading to the formation of iCCA. It has been recently estimated based on abundant epidemiological data that the association between HBV infection and iCCA is strong with an odds ratio of about 4.5. The HBV-associated mechanisms that lead to iCCA are under intense investigation. The diagnosis of iCCA in the context of chronic liver disease is challenging and often requires histological confirmation to distinguish from hepatocellular carcinoma. It is currently unclear whether antiviral treatment for HBV can decrease the incidence of iCCA. In terms of management, surgical resection remains the mainstay of treatment. There is a need for effective treatment modalities beyond resection in both first- and second-line treatment. In this review, we summarize the epidemiological evidence that links the two entities, discuss the pathogenesis of HBV-associated iCCA, and present the available data on the diagnosis and management of this cancer.

A 56-year-old man with chronic renal failure due to diabetic nephropathy had received maintenance dialysis (every 4 h, three times/week). A hypoechoic tumor measuring 67 × 50 mm in the right lobe of the liver was discovered following routine abdominal ultrasonography. Dynamic computed tomography showed a low-density liver tumor, enlarged hilar lymph node, and a small nodule on the dorsal side of the lower lobe of the left lung. Histopathological examination of the liver tumor revealed intrahepatic cholangiocarcinoma. We developed a chemotherapy treatment plan with gemcitabine, which can be performed concurrently with hemodialysis. Gemcitabine (1000 mg/m2, three times/cycle) was administered on Friday afternoon, and hemodialysis was performed on Tuesday, Thursday, and Saturday. Anemia and hypotension occurred after gemcitabine administration. Therefore, the dose of darbepoetin alpha was increased, and packed red blood cells were transfused. The patient was treated with gemcitabine for approximately 5 and a half months until computed tomography findings showed progressive disease; the survival time after treatment start was 8 months. Chemotherapy using gemcitabine has not been established in dialysis patients and has little evidence. We report a case of unresectable intrahepatic cholangiocarcinoma that developed during maintenance dialysis and was treated using gemcitabine chemotherapy.

Background Programmed death- ligand 1 (PD-L1) seems to be associated with the immune escape of tumors, and immunotherapy may be a favorable treatment for PD-L1-positive patients. We evaluated intrahepatic cholangiocarcinoma (ICC) specimens for their expression of PD-L1, infiltration of CD8+ T cells, and the relationship between these factors and patient survival. Methods In total, 69 resections of ICC were stained by immunohistochemistry for PD-L1, programmed death factor-1 (PD-1), and CD8+ T cells. CD8+ T-cell densities were analyzed both within tumors and at the tumor-stromal interface. Patient survival was predicted based on the PD-L1 status and CD8+ T-cell density. Results The expression rate of PD-L1 was 12% in cancer cells and 51% in interstitial cells. The expression rate of PD-1 was 30%, and the number of CD8+ T-cells increased with the increase of PD-L1 expression (p Conclusions The expression of PD-L1 in the tumor is related to poor OS, and the number of tumor or interstitial CD8+ T-cells is related to poor OS and DFS. For patients who lose their chance of surgery, PD-L1 immunosuppressive therapy may be the focus of future research as a potential treatment.

BackgroundAt diagnosis, the majority of patients with intrahepatic cholangiocarcinoma (IHCC) present with advanced disease and a poor prognosis. Comprehensive genomic profiling (CGP) early in the disease course may increase access to targeted therapies and clinical trials; however, unresolved issues remain surrounding the optimal biopsy type to submit for CGP.Patients and MethodsMutational frequencies between primary tumor biopsies (Pbx), metastatic biopsies (Mbx), and liquid biopsies (Lbx) in 1,632 patients with IHCC were compared.ResultsPotentially actionable alterations were found in 52%, 34%, and 35% of patients in the Pbx, Mbx, and Lbx cohorts, respectively. In Pbx, Mbx, and Lbx, FGFR2 rearrangements were found in 9%, 6%, and 4%, and IDH1 mutations were identified in 16%, 5%, and 9% patients, respectively. Moreover, alterations in FGFR2 and IDH1 were significantly associated with distinct ancestries, including 2.1-fold enrichment for FGFR2 rearrangements in patients with African ancestry and 1.5-fold enrichment for IDH1 mutations in patients with admixed American (Hispanic) ancestry. Finally, the publication of biomarker-driven clinical trials in IHCC correlated with changing CGP testing patterns. Significant correlations between patient characteristics and IHCC trial disclosures were observed, including a significant decrease from time between biopsy and CGP testing, and more frequent testing of primary versus metastatic samples.ConclusionOverall, because of the high likelihood of identifying actionable genomic alterations, CGP should be considered for the majority of patients with inoperable IHCC, and Lbx and Mbx can be considered as part of the diagnostic suite.Implications for PracticeComprehensive genomic profiling (CGP) should be considered for all patients with intrahepatic cholangiocarcinoma (IHCC) or suspected IHCC, as actionable alterations were commonly found in multiple genes and a wide variety of FGFR2 fusion partners were identified. The disclosure of IHCC trial data correlated with increased use of CGP, an encouraging trend that moves new therapeutic options forward for rare cancers with a rare biomarker. Although tissue from the primary lesion may identify actionable alterations at higher rates, CGP of a liquid biopsy or metastatic site can be considered, particularly if the primary tissue block is exhausted.

BACKGROUND AND AIMS Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. APPROACH AND RESULTS For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P

Changes in immune cell and inflammation-associated protein levels, either independently or in combination, are commonly used as prognostic factors for various cancers. The ratio of lymphocyte count to C-reactive protein concentration (lymphocyte–CRP ratio; LCR) is a recently identified prognostic marker for several cancers. Here, we examined the prognostic value of LCR and its relationship to various aspects of the tumor immune microenvironment in patients with intrahepatic cholangiocarcinoma (ICC). This was a single-center, retrospective study of patients who underwent surgical resection for ICC between 1998 and 2018. Patients were dichotomized into high- and low-LCR status groups, and the relationships between LCR status, prognosis, and other clinicopathological characteristics were analyzed. Tumor-infiltrating CD8+ and FOXP3s+ lymphocytes and tumor expression of CD34 and programmed death-ligand 1 were evaluated by immunohistochemical staining of resected tumors. A total of 78 ICC patients were enrolled and assigned to the high (n = 44)- and low (n = 34)-LCR groups. Compared with the high-LCR group, patients in the low-LCR group had a significantly higher serum CA19-9 level (median 20.6 vs. 77.3 U/mL, P = 0.0017) and larger tumor size (median 3.5 vs. 5.5 cm, P = 0.0018). LCR correlated significantly with tumor microvessel density (r = 0.369, P = 0.0009) and CD8+ T lymphocyte infiltration (r = 0.377, P = 0.0007) but not with FOXP3+ T lymphocyte infiltration or tumor PD-L1 expression. Low-LCR status was significantly associated with worse overall survival by multivariate analysis (P = 0.0348). Low-LCR status may reflect a poor anti-tumor immune response and predict worse outcomes in ICC patients.

Although lymph node metastasis is a known factor predictive of a poor prognosis after radical surgery for intrahepatic cholangiocarcinoma (ICC), few studies have investigated lymph node dissection (LND) areas for accurate staging. The aim of this study was to identify the optimal LND level for ICC considering lymphatic flow. Clinical characteristics and pathologic nodal status (presence of metastasis) for 163 patients were reviewed according to tumor location. In the node-positive (N1) group, the distribution of metastatic nodes was described. The coverage of metastatic nodes according to dissection level was assessed, and the minimum dissection level for accurate ICC staging was estimated accordingly. For validation, the node-negative (N0) group was divided into two subgroups according to the estimated dissection level, and survival outcomes were compared. In the N1 group, expanding dissection to stations no. 12 and 8 covered 82.0% (n = 50) of metastatic cases regardless of tumor location. In survival analysis of N0 group, patients who underwent LND covering stations no. 8+12 showed better disease-free survival (DFS) and overall survival (OS), although the differences were not statistically significant (DFS: covering no. 12+8 vs. not covering no. 12+8, 109.0 months [24.2–193.8] vs. 33.0 months [10.3–55.7], p = 0.078; OS: covering no. 12+8 vs. not covering no. 12+8, 180.0 months [21.6–338.4] vs. 73.0 months [42.8–103.2], p = 0.080). LND including at least stations no. 12 (hepatoduodenal ligament) and 8 (common hepatic artery), regardless of tumor location, is recommended for accurate staging in ICC patients.

BACKGROUND/PURPOSE The objective of this study was to determine the frequency and predictors of biliary tract cancer (BTC) with deficient DNA mismatch repair (dMMR) in Japan. METHODS Immunostaining and microsatellite instability analysis were performed for mismatch repair-related proteins in tissue specimens from 662 patients who underwent surgery for BTC between 2001 and 2017 to identify dMMR-BTC. We compared dMMR-BTC and proficient MMR (pMMR)-BTC based on patient demographics, pathological features, and host immune responses characterized by the percentage of stromal tumor infiltrating lymphocytes (sTIL percentage) and tertiary lymphoid structures (TLS). RESULTS The incidence of dMMR-BTC was 2.3%. Significant predictors of dMMR-BTC were its primary lesion being intrahepatic cholangiocarcinoma (odds ratio [OR] 6.34, P = .004), presence of signet ring cell component (OR 35.62, P

Summary Background & aims Sarcopenia is characterized by loss of skeletal muscle mass and associated with poor postoperative outcomes. This study aimed to investigate the prognostic value of preoperative albumin-globulin score (AGS), skeletal muscle index (SMI) as well as their combination in patients with intrahepatic cholangiocarcinoma (ICC) treated with surgical resection. Methods A total of 613 newly diagnosed ICC patients from two centers were retrospectively analyzed (460 in discovery cohort and 153 in validation cohort). The plain computed tomography images were used to measure SMI. The effect of AGS, SMI and CAS grade on clinicopathological characteristics and long-term outcomes of patients with ICC were analyzed. Results The SMI was significantly greater in males than in females. Patients with decreased AGS, increased SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS). Stratefied by CAS grade, 68 (14.8%) patients in grade 1 were associated with increased body mass index (BMI) and best postoperative prognosis, whereas 194 (42.1%) patients in grade 3 were linked to worst OS and RFS. The CAS grade showed a promising accuracy in predicting OS and RFS of ICC patients (area under curves [AUCs] were 0.732 and 0.768). Multiple tumors, MVI and elevated CAS grades were identified as independent risk factors for OS and RFS of ICC patients. These results were confirmed by validation cohort. Conclusion The present study provided compelling evidence that a novel index based on combination of preoperative AGS and SMI was closely related to postoperative long-term outcomes for surgically treated ICC patients. Preoperative evaluation of CAS grade may be useful for risk classification and clinical therapeutic decision-making for ICC patients.

Background This study aimed to investigate the prognostic impact of parenchyma-sparing hepatectomy (PSH) on solitary small intrahepatic cholangiocarcinoma (ICC). Methods A total of 184 patients with solitary small ICC (≤ 5 cm) from 2009 to 2017 were included. Short- and long-term outcomes were compared between PSH and Non-PSH approach. Results 95 (51.6%) patients underwent PSH and 89 (48.4%) patients underwent Non-PSH for solitary small ICC. PSH was associated with less intraoperative blood loss (212.9 mL versus 363.5 mL, P=0.038), lower transfusion rate (7.4% versus 16.9%, P=0.048), without increasing the frequency of tumor recurrence (60.0% versus 58.4%). No significant differences were observed in overall survival (OS), recurrence-free survival (RFS) and liver RFS (P = 0.627, 0.769 and 0.538, respectively). 109 (59.2%) patients experienced recurrence, of these, 67 (36.4%) were intrahepatic recurrence. Subgroup analysis of patients with liver-only recurrence demonstrated an increased likelihood of repeat hepatectomy for PSH compared to Non-PSH (21.2% versus 2.9%, P = 0.031), thus resulting in improved liver OS (P = 0.016). Conclusion PSH was associated with improved perioperative outcomes but it did not increase liver recurrence rates. PSH offered an increased rate of salvage hepatectomy for recurrent tumor, thus improving long-term survival in cases in which liver recurrence occurred.