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Background Liver surgery after radioembolization (RE) entails highly demanding and challenging procedures due to the frequent combination of large tumors, severe RE-related adhesions, and the necessity of conducting major hepatectomies. Laparoscopic liver resection (LLR) and its associated advantages could provide benefits, as yet unreported, to these patients. The current study evaluated feasibility, morbidity, mortality, and survival outcomes for major laparoscopic liver resection after radioembolization. Material and methods In this retrospective, single-center study patients diagnosed with hepatocellular carcinoma, intrahepatic cholangiocarcinoma or metastases from colorectal cancer undergoing major laparoscopic hepatectomy after RE were identified from institutional databases. They were matched (1:2) on several pre-operative characteristics to a group of patients that underwent major LLR for the same malignancies during the same period but without previous RE. Results From March 2011 to November 2020, 9 patients underwent a major LLR after RE. No differences were observed in intraoperative blood loss (50 vs. 150 ml; p = 0.621), operative time (478 vs. 407 min; p = 0.135) or pedicle clamping time (90.5 vs 74 min; p = 0.133) between the post-RE LLR and the matched group. Similarly, no differences were observed on hospital stay (median 3 vs. 4 days; p = 0.300), Clavien–Dindo ≥ III complications (2 vs. 1 cases; p = 0.250), specific liver morbidity (1 vs. 1 case p = 1.000), or 90 day mortality (0 vs. 0; p = 1.000). Conclusion The laparoscopic approach for post radioembolization patients may be a feasible and safe procedure with excellent surgical and oncological outcomes and meets the current standards for laparoscopic liver resections. Further studies with larger series are needed to confirm the results herein presented.

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 While minimally invasive liver resection (MILR) vs. open approach (OLR) has been shown to be safe, the perioperative and oncologic safety for intrahepatic cholangiocarcinoma (ICC) specifically, necessitating often complex hepatectomy and extended lymphadenectomy, remains ill-defined. Methods The National Cancer Database was queried for patients with ICC undergoing liver resection from 2010 to 2016. After 1:1 Propensity Score Matching (PSM), Kruskal-Wallis and χ2 tests were applied to compare short-term outcomes. Kaplan-Meier survival analyses and Cox multivariable regression were performed. Results 988 patients met inclusion criteria: 140 (14.2%) MILR and 848 (85.8%) OLR resulting in 115 patients MILR and OLR after 1:1 PSM with c-index of 0.733. MILR had lower unplanned 30-day readmission [OR 0.075, P = 0.014] and positive margin rates [OR 0.361, P = 0.011] and shorter hospital length of stay (LOS) [OR 0.941, P = 0.026], but worse lymph node yield [1.52 vs 2.07, P = 0.001]. No difference was found for 30/90-day mortality. Moreover, multivariate analysis revealed that MILR was associated with poorer overall survival compared to OLR [HR 2.454, P = 0.001]. Subgroup analysis revealed that survival differences from approach were dependent on major hepatectomy, tumor size > 4 cm, or negative margins. Conclusion MILR vs. OLR is associated with worse lymphadenectomy and survival in patients with ICC greater than 4 cm requiring major hepatectomy. Hence, MILR major hepatectomy for ICC should only be approached selectively and if surgeons are able to perform an appropriate lymphadenectomy.

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.

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

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

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.

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.

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.

To clarify whether the preoperative lymphocyte/C-reactive protein (CRP) ratio (LCR) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (IHCC), and investigate its mechanism via tumor-infiltrating lymphocytes. The subjects of this retrospective study were 42 patients who had undergone hepatectomy for IHCC. We divided the patients into low LCR and high LCR groups (cutoff value: 8780) and analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated the levels of stromal tumor-infiltrating lymphocytes (TILs) and CD8+ TILs in surgical specimens, and the relationship between LCR and TILs. A low LCR was identified in 21 patients and was significantly correlated with older age, a high CRP-albumin ratio, and advanced disease stage, and was a prognostic factor for OS and DFS. Multivariate analysis revealed that a low LCR was an independent prognostic factor for worse OS (HR 10.40, P = 0.0077). Although the LCR and levels of stromal TILs were not significantly related, LCR and levels of CD8+ TILs were significantly related (P = 0.0297). The preoperative LCR may predict the postsurgical prognosis of patients with IHCC and reflect the CD8+ TILs.

Current prognostic systems for intrahepatic cholangiocarcinoma (IHCC) rely on surgical pathology data and are not applicable to a preoperative setting. We aimed to develop and validate preoperative models to predict postsurgical outcomes in mass-forming IHCC patients based on clinical, radiologic, and radiomics features. This multicenter retrospective cohort study included patients who underwent curative-intent resection for mass-forming IHCC. In the development cohort (single institution data), three preoperative multivariable Cox models for predicting recurrence-free survival (RFS) were constructed, including the clinical-radiologic, radiomics, and clinical-radiologic-radiomics (CRR) models based on clinical and CT findings, CT-radiomics features, and a combination of both, respectively. Model performance was evaluated in the test cohort (data from five institutions) using Harrell’s C-index and compared with postoperative prognostic systems. A total of 345 patients (233, development cohort; 112, test cohort) were evaluated. The clinical-radiologic model included five independent CT predictors (infiltrative contour, multiplicity, periductal infiltration, extrahepatic organ invasion, and suspicious metastatic lymph node) and showed similar performance in predicting RFS to the radiomics model (C-index, 0.65 vs. 0.68; p = 0.43 in the test cohort). The CRR model showed significantly improved performance (C-index, 0.71; p = 0.01) than the clinical-radiologic model and demonstrated similar performance to the postoperative prognostic systems in predicting RFS (C-index, 0.71–0.73 vs. 0.70–0.73; p ≥ 0.40) and overall survival (C-index, 0.68–0.71 vs. 0.64–0.74; p ≥ 0.27) in the test cohort. A model integrating clinical, CT, and radiomics information may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming IHCC. • The radiomics analysis had incremental value in predicting recurrence-free survival of patients with intrahepatic mass-forming cholangiocarcinoma. • The clinical-radiologic-radiomics model demonstrated similar performance to the postoperatively available prognostic systems (including 8th AJCC system) in predicting recurrence-free survival and overall survival. • The clinical-radiologic-radiomics model may be useful for the preoperative assessment of postsurgical outcomes in patients with mass-forming intrahepatic cholangiocarcinoma.

Purpose: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative. Materials and methods: A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures. Results: A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2months while after TARE was 13.5months (95%C.I.: 11.4–16.1). The survival difference was small (d = 0.112) at 1year and negligible at 2years (d = 0.028) and at 3years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314). Conclusion: In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).

To eliminate the effects of field strength in determining the diagnostic performance of the LI-RADS version 2018 (LI-RADS v2018) in differentiating hepatocellular carcinoma (HCC) from non-HCC primary liver malignancy in high-risk patients. Patients who were pathologically confirmed intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA) were retrospectively reviewed. Patients with HCC were matched to the iCCA or cHCC-CCA patients on age, tumor size, MR scanner, and number of tumors. Two readers independently evaluated the lesions according to LI-RADS v2018. Diagnostic performance of LI-RADS v2018 in differentiating HCC from non-HCC primary liver malignancy were analyzed. A total of 198 patients with 204 lesions (102 HCCs, 78 iCCAs, and 24 cHCC-CCAs) were enrolled. The sensitivity and specificity of LR-5 or LR-TIV (definitely due to HCC) in diagnosing HCC were 68.63% and 85.29%, respectively. LR-M or LR-TIV (may be due to non-HCC malignancy) had a sensitivity of 72.55% and a specificity of 86.27% in diagnosing non-HCC malignancy. The sensitivity of LR-M or LR-TIV (may be due to non-HCC malignancy) for iCCA and cHCC-CCA was 82.05% and 41.67%, respectively. Nearly half (11/24, 45.83%) of cHCC-CCAs were categorized as LR-5. Three tesla MR showed higher sensitivity than 1.5 T in diagnosing HCC (80.00% vs 57.69%, P = 0.015). When the effect of field strength was eliminated, LI-RADS v2018 demonstrated high specificity but suboptimal sensitivity in distinguishing HCC from non-HCC primary liver carcinomas. Most iCCAs were categorized as LR-M or LR-TIV (may be due to non-HCC malignancy). However, nearly half of cHCC-CCAs were assigned as LR-5.

Background Robotic hepatectomy (RH) is increasingly utilized for minor and major liver resections. The IWATE criteria were developed to classify minimally invasive liver resections by difficulty. The objective of this study was to apply the IWATE criteria in RH and to describe perioperative and oncologic outcomes of RH over the last decade at our institution. Methods Perioperative and oncologic outcomes of patients who underwent RH between 2011 and 2019 were retrospectively collected. The difficulty level of each operation was assessed using the IWATE criteria, and outcomes were compared at each level. Univariate linear regression was performed to characterize the relationship between IWATE criteria and perioperative outcomes (OR time, EBL, and LOS), and a multivariable model was also developed to address potential confounding by patient characteristics (age, sex, BMI, prior abdominal surgery, ASA class, and simultaneous non-hepatectomy operation). Results Two hundred and twenty-five RH were performed. Median IWATE criteria for RH were 6 (IQR 5–9), with low, intermediate, advanced, and expert resections accounting for 23% (n = 51), 34% (n = 77), 32% (n = 72), and 11% (n = 25) of resections, respectively. The majority of resections were parenchymal-sparing approaches, including anatomic segmentectomies and non-anatomic partial resections. 30-day complication rate was 14%, conversion to open surgery occurred in 9 patients (4%), and there were no deaths within 30 days postoperatively. In the univariate linear regression analysis, IWATE criteria were positively associated with OR time, EBL, and LOS. In the multivariable model, IWATE criteria were independently associated with greater OR time, EBL, and LOS. Two-year overall survival for hepatocellular carcinoma and intrahepatic cholangiocarcinoma was 94% and 50%, respectively. Conclusion In conclusion, the IWATE criteria are associated with surgical outcomes after RH. This series highlights the utility of RH for difficult hepatic resections, particularly parenchymal-sparing resections in the posterosuperior sector, extending the indication of minimally invasive hepatectomy in experienced hands and potentially offering select patients an alternative to open hepatectomy or other less definitive liver-directed treatment options.

To evaluate targetoid appearance on T2-weighted imaging and signs of tumor vascular involvement as potential new LI-RADS features for differentiating hepatocellular carcinoma (HCC) from other non-HCC primary liver carcinomas (PLCs). This IRB-approved, retrospective study was performed at two liver transplant centers. The final population included 375 patients with pathologically proven lesions imaged between 2007 and 2017 with contrast-enhanced CT or MRI. The cohort consisted of 165 intrahepatic cholangiocarcinomas and 74 combined hepatocellular-cholangiocarcinomas, with the addition of 136 HCCs for control. Two abdominal radiologists (R1; R2) independently reviewed the imaging studies (112 CT; 263 MRI) and recorded the presence of targetoid appearance on T2-weighted images and features of tumor vascular involvement including encasement, narrowing, tethering, occlusion, and obliteration. The sensitivity and specificity of each feature were calculated for the diagnosis of non-HCC PLCs. Cohen’s kappa (k) test was used to assess inter-reader agreement. The sensitivity of targetoid appearance on T2-weighted images for the diagnosis of non-HCC PLCs was 27.5% and 32.6% (R1 and R2) and the specificity was 98.2% and 97.3% (R1 and R2). Among the features of tumor vascular involvement, those providing the highest sensitivity for non-HCC PLCs were vascular encasement (R1: 34.3%; R2: 37.2%) and obliteration (R1: 25.5%; R2: 29.7%). The highest specificity for non-HCC PLCs was provided by tethering (R1: 100%; R2: 97.1%) and occlusion (R1: 99.3%; R2: 99.3%). The inter-reader agreement was moderate to substantial (k = 0.48–0.77). Targetoid appearance on T2-weighted images and features of tumor vascular involvement demonstrated high specificity for non-HCC malignancy. • Targetoid appearance on T2-weighted imaging and signs of tumor vascular involvement have high specificity (92–100%) for the diagnosis of non-HCC PLCs, regardless of the presence of liver risk factors. • In the subset of patients with risk factors for HCC, the sensitivity of signs of tumor vascular involvement decreases for both readers (1.7–20.3%), while the specificity increases reaching values higher than 94.2%. • The inter-reader agreement is substantial for targetoid appearance on T2-weighted images (k = 0.74) and moderate to substantial for signs of tumor vascular involvement (k = 0.48–0.77).

Elevated expression of eukaryotic initiation factor 3c (eIF3C) was recently uncovered to promote several types of cancer progression by inducing cell proliferation. Here, we aimed to assess the expression and prognostic value of eIF3C in intrahepatic cholangiocarcinoma (ICC) patients. Expression of eIF3C was analyzed by immunohistochemistry in tissue microarrays (TMAs) containing 138 ICC and paired peritumoral tissues from ICC patients. Then, the roles of eIF3C in ICC cells were investigated by RNA interference, and the relationship between the eIF3C and KI67 expression was explored in ICC cells and tissues. Finally, the relation between the eIF3C level and clinicopathologic features of ICC was probed, and Kaplan–Meier and Cox’s analyses were performed to assess the prognostic merit of eIF3C and KI67 in ICC patients. The expression of eIF3C was elevated in ICC tissues compared to paired peritumoral tissues, which was consistent with the result from the GEPIA database. The downregulation of eIF3C in ICC cells impaired the cellular invasion, metastasis, colony formation, and proliferation. Moreover, we further found a positive relationship between the eIF3C and KI67 expression in ICC cells and tissues. The expression of eIF3C in ICC tissues was positively correlated with lymphatic metastasis (p = 0.049), and the high level of KI67 was frequently found in ICC patients with the large tumor (p = 0.028), high serum AFP (p = 0.019), or lymphatic metastasis (p = 0.039). Notably, patients with the eIF3C or KI67 overexpression had shorter overall survival and higher disease-free survival rates than those with low expression of eIF3C or KI67, and the combination of eIF3C or KI67 expression was an independent parameter for predicting the prognosis and recurrence of ICC patients. Elevated eIF3C expression promotes ICC development, and combination of eIF3C and KI67 is a valuable predictor of the survival and recurrence of ICC patient.

Hepatolithiasis is associated with the development of intrahepatic cholangiocarcinoma (ICC). This study sought to investigate risk factors of ICC for hepatolithiasis after partial hepatectomy (PH) and to develop a model for predicting ICC risk. Data on consecutive patients who underwent PH for hepatolithiasis at the Eastern Hepatobiliary Surgery Hospital between January 2009 and December 2011 were reviewed. Independent risk factors of ICC identified by Cox regression model were used to develop a nomogram in predicting ICC after PH for hepatolithiasis. Of 2056 patients, 168 developed ICC at a median follow-up of 7.2 years. The cumulative incidences of ICC at 3, 5, and 8 years after PH for hepatolithiasis were 3.0%, 6.5%, and 12.9%, respectively. Independent risk factors of ICC were identified to be a long duration of hepatolithiasis-related symptoms (hazard ratio, 1.088 [95% confidence interval, 1.057–1.120]), metabolic syndrome (2.036 [1.210–3.425]), a high neutrophil-to-lymphocyte ratio (1.250 [1.009–2.816] for 3–5 vs ≤3; 1.538 [1.048–2.069] for ≥5 vs ≤3), hepatic atrophy (1.711 [1.189–2.462]), segmental intensity differences (1.513 [1.052–2.176]), persistent biliary strictures (2.825 [1.480–5.391]), and residual stone disease (2.293 [1.511–3.481]). By incorporating these factors, a constructed nomogram showed a concordance index of 0.721 to predict ICC. The calibration plots demonstrated good agreement between observed and predicted morbidities. The optimal cutoff point for the nomogram was 48 in differentiating between high and low-risk of ICC. A nomogram for predicting ICC after PH for hepatolithiasis was constructed based on risk factors of developing ICC. Patients with a nomogram point of ≥48 were predicted to have a high risk of ICC.

Multiple tumor foci (MTF) in intrahepatic cholangiocarcinoma (ICC), including satellitosis and true multifocality, is a known negative prognostic factor and can inform pre-operative decision-making. Lack of standardized pre-operative liver staging practices may contribute to undiagnosed MTF and poor outcomes. We sought to investigate the sensitivity of different cross-sectional imaging modalities for MTF at our institution. We identified n = 52 patients with ICC who underwent curative-intent resection from 2004 to 2017 in a multidisciplinary hepato-pancreato-biliary cancer program. Timing and modality of pre-operative imaging were recorded. Blinded review of imaging was performed and modalities were evaluated for false-negative rate (FNR) in detecting MTF, satellitosis, and true multifocality. Forty-one (79%) patients underwent CT and 20 (38%) underwent MRI prior to hepatectomy. MTF was pre-operatively identified in six (12%) patients. An additional seven patients had MTF discovered on final surgical pathology, despite a median interval from CT/MRI to surgery of 20 days. On blinded review the FNR of MRI compared to CT for multifocality was 0% vs. 38%, 50% vs 80% for satellitosis, and 22% vs 46% for MTF as a whole. CT is inadequate for pre-operative diagnosis of MTF in resectable ICC, even when performed within 30 days of hepatectomy. We recommend liver-protocol MRI as the standard pre-operative imaging modality in non-metastatic ICC.

Purpose Liver transplantation (LT) has gained ground as a treatment for cholangiocarcinoma. LT has achieved an established role as curative treatment for unresectable hilar cholangiocarcinoma (hCCA), and there are emerging data supporting its use in select patients with intrahepatic cholangiocarcinoma (iCCA). This review explores the current frontiers and future directions of LT for CCA. Recent Findings Results of retrospective studies support randomized trials of LT for resectable hCCA. Select patients with iCCA who have small tumors or favorable disease biology, as demonstrated by response to neoadjuvant therapy, have long-term survival after LT. Discoveries in the biology of iCCA show patients with FGFR and other genetic abnormalities have improved outcomes and may benefit from targeted therapies. Summary The outcomes of LT for CCA support its increased utilization. Policies should be considered to increase accessibility of donor organs for patients with iCCA.

We aimed to investigate contemporary management and outcomes of bile leakage in patients who underwent hepatectomy with hepaticojejunostomy for liver malignancy. The NSQIP database was used to study clinical data of patients who underwent a hepatectomy with hepaticojejunostomy for a primary hepatobiliary cancer and developed bile leakage between 1/2014 and 12/2017. Multivariate regression analysis was performed to investigate outcomes. Five hundred patients underwent a hepatectomy with hepaticojejunostomy for a malignant primary hepatobiliary cancer (41% intrahepatic cholangiocarcinoma, 38.2% hilar cholangiocarcinoma, 9.8% hepatocellular carcinoma, 6% gallbladder cancer, and 5% others). The rate of bile leakage was 33.4%. Most patients (90.4%) did not require re-exploration. In 77 of 157 patients (49.1%), bile leakages were contained with intraoperatively placed drain(s) and no additional surgical intervention was required. A total of 71 patients (42.5%)—including 64 patients with intraoperative drains—required interventional radiology (IR)-guided drainage, with a 88.7% success rate. A total of 16 patients (9.6%) required re-exploration to control the leakage, with 8 of them having undergone failed IR-drainage. When running multivariate analysis, post-hepatectomy liver failure (AOR: 158.26, P

Oncogene : including Oncogene reviews 40(5), 899-908 (2021). doi:10.1038/s41388-020-01578-4, Published by Springer Nature, London

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive hepatic malignancy. An up-to-date systematic review and meta-analysis was conducted aiming to compare outcomes between laparoscopic (LLR) and open liver resection (OLR) for patients with iCCA. A systematic literature search of Medline, Scopus, Google Scholar, and Cochrane databases was performed. A total of 8 studies comprising 2872 patients, who underwent LLR or OLR for iCCA, were included in our meta-analysis. LLR patients had smaller tumors [mean difference (MD): − 1.17 cm, 95% confidence intervals (CI) − 1.77 to − 0.57, p = 0.0001], underwent major resections less frequently [risk ratio (RR): 0.75, 95% CI 0.67–0.83, p

The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy is controversial, and the T category in the American Joint Committee on Cancer (AJCC) stage for ICC is a topic of debate. Data from 611 T1-2N0M0 ICC patients classified by the AJCC 8th edition who underwent hepatectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database during 1988–2015. Cancer-specific survival was evaluated using Kaplan-Meier analysis. The optimal cutoff value of solitary tumor size was used an adjusted p value approach to discriminating patient survival. In the AJCC 8th staging system, using a 5-cm cut-off value of tumor size for solitary ICC without vascular invasion (S/VI–) was not associated with survival in T1 category (p = 0.201), and multifocal ICC with vascular invasion had a worse survival than solitary ICC with vascular invasion (S/VI+) in T2 category (p = 0.014). Tumor size was a prognostic factor for both S/VI– and S/VI+, the optimal cutoff value of tumor size was obtained 8 cm for S/VI– and 3 cm for S/VI+. S/VI– ≤ 8 cm had a similar survival to S/VI+ ≤ 3 cm (p = 0.126), S/VI– > 8 cm had a similar survival to S/VI+ > 3 cm (p = 0.655), and multifocal ICC had a similar survival with S/VI– > 8 cm (p = 0.159) and S/VI+ > 3 cm (p = 0.196). When the cohort was divided into two groups—new T1 (S/VI– ≤ 8 cm and S/VI+ ≤ 3 cm) and new T2 (S/VI– > 8 cm, S/VI+ > 3 cm and multifocal ICC)—significant survival difference was observed (p < 0.0001). The discriminatory power of the AJCC 8th edition for solitary ICC could be further enhanced by subdividing tumors according to size and vascular invasion (8 cm for S/VI– and 3 cm for S/VI+).

This study aimed to compare the performance of 68Ga-labelled fibroblast activating protein inhibitor (FAPI) PET and 18F-FDG PET for imaging of hepatic tumours. We prospectively assessed 20 patients with suspected intrahepatic lesions. Tumour radiological features, pathology, or follow-up examinations were assessed as ground truth in correlation with PET scans. Semiquantitative analysis was additionally performed by measuring the standardised uptake value (SUV). Tumour-to-liver background ratios (TBR) were calculated and compared between 68Ga-FAPI PET and 18F-FDG PET. FAPI expression was assessed by immunochemistry in samples obtained from 7 patients with hepatocellular carcinomas (HCC)/intrahepatic cholangiocarcinoma (ICC) or granulomas. Primary intrahepatic tumours, including 16 HCC in 14 patients and 4 ICC in 3 patients with extrahepatic metastases, were determined by histology (n = 14) and clinical examinations (n = 3). Based on visual analysis, 17 patients presented elevated 68Ga-FAPI uptake (sensitivity: 100%, specificity: 100%), while 7 patients presented 18F-FDG avid tumours (sensitivity: 58.8%, specificity: 100%). 68Ga-FAPI PET/CT identified 17 extrahepatic metastases vs. 13 in 18F-FDG PET/CT in 2 ICC patients. Three benign liver nodules in three patients showed negligible uptake in dual-PET scans. The SUVmax_HCC = 8.47 ± 4.06 and TBRmax_HCC = 7.13 ± 5.52, and SUVmax_ICC = 14.14 ± 2.20 TBRmax_ICC = 26.46 ± 4.94 in 68Ga-FAPI-04 PET/CT were significantly higher than the 18F-FDG uptake presenting SUVmax_HCC = 4.86 ± 3.58 and TBRmax_HCC = 2.39 ± 2.21, and SUVmax_ICC = 9.19 ± 3.60 and TBRmax_ICC = 2.39 ± 2.21 (all p values

To determine whether albumin–bilirubin (ALBI) grade could be used to predict the outcomes of patients with intrahepatic cholangiocarcinoma (ICC) who underwent ultrasound-guided percutaneous microwave ablation (MWA). This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. We studied 52 treatment-naive patients with 74 ICC lesions according to the Milan criteria who subsequently underwent MWA from April 2011 to March 2018. Overall survival (OS) and recurrence-free survival (RFS) were compared in groups classified by Child–Pugh score and ALBI grade, which were statistically analyzed with the log-rank test. Cox proportional hazard regression analyses were used to determine the prognostic factors for survival in patients with ICC. The median follow-up time was 21.2 months (3.2–78.7 months). Seventeen patients died during this period. After MWA, the cumulative 1-, 3-, and 5-year OS rates were 87.4%, 51.4%, and 35.2%, respectively, and the cumulative 1-, 3-, and 5-year RFS rates were 68.9%, 56.9%, and 56.9%, respectively. The major complication rate was 3.8% (2/52). Stratified according to ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 95.5%, 72.4%, and 72.4% for patients with ALBI grade 1 and 62.5%, 40.6%, and 36.3% for patients with ALBI grade 2, respectively, showing a significant difference (P = 0.006). Multivariate analysis results showed that older age (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11–2.82; P = 0.002), tumor size ≥ 3 cm in diameter (HR: 11.33, CI: 2.24–34.52; P = 0.021) and ALBI grade (HR: 8.23, CI: 1.58–58.00; P = 0.004) may be predictors of poor OS. ALBI grade was validated as a significant biomarker for predicting survival in ICC patients within the Milan criteria who underwent MWA.

A 71-year-old man on prednisolone for immunoglobulin (Ig) G4-related renal disease showed increased carbohydrate antigen (CA) 19–9 level; abdominal enhanced computed tomography (CT) showed a lesion in the left lateral segment and dilatation of the peripheral biliary duct. He was referred to our hospital for detailed examination for suspected intrahepatic cholangiocarcinoma. CT and magnetic resonance imaging findings were similar to those for intrahepatic cholangiocarcinoma. However, endoscopic retrograde cholangiopancreatography showed a smooth narrowing of the bile duct which suggested inflammatory disease. Liver biopsy was performed; IgG4-related hepatic inflammatory pseudotumor (IPT) was diagnosed. IgG4-related hepatic IPTs are rare diseases that develop in association with the development of sclerosing cholangitis. Most of these lesions develop in the hepatic hilum and the imaging findings of these tumors are similar to those of hilar cholangiocarcinomas. Thus, hepatic IPTs are difficult to differentiate from malignancy; in some cases, surgical resection has been considered for establishing the diagnosis. In the present case, we could diagnose hepatic IPT on the basis of liver biopsy, which is the recommended approach in cases of suspected hepatic IPT.

To investigate and compare radiomics and clinical information for preoperative prediction of futile resection in intrahepatic cholangiocarcinoma (ICC). A total of 203 ICC patients from two centers were included and randomly allocated with a ratio of 7:3 into the training cohort and the validation cohort. Clinical characteristics and radiomics features were selected using random forest algorithm and logistic models to construct a clinical model and a radiomics model, respectively. A combined logistic model that incorporated the developed radiomics signature and clinical risk factors was then built. The performance of these models was evaluated and compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). The radiomics model showed a higher AUC than the clinical model in the validation cohort (AUC: 0.804 (95% CI: 0.697, 0.912) vs. 0.590 (95% CI: 0.415, 0.765), p = 0.043) for predicting futile resection in ICC. The radiomics model reached a sensitivity of 0.846 (95% CI: 0.546, 0.981) and a specificity of 0.771 (95% CI: 0.627, 0.880) in the validation cohort. Moreover, the radiomics model had comparable AUCs with the combined model in training and validation cohorts. We presented an internally validated radiomics model for the prediction of futile resection in ICC patients. Compared with clinical information, radiomics using CT images had greater potential for predicting futile resection accurately before surgery. • Radiomics model using CT images could predict futile resection in intrahepatic cholangiocarcinoma preoperatively. • Radiomics model using CT images was superior to clinical information for predicting futile resection accurately before surgery.

The high technical difficulty of using a laparoscopic approach to reach the posterosuperior liver segments is mainly associated with their poor accessibility. This study was performed to analyze correlations between anthropometric data and intraoperative outcomes.All patients who underwent segmentectomy or wedge laparoscopic liver resection (LLR) of segments seven and/or eight from June 2012 to November 2019 were retrospectively analyzed. The exclusion criteria were intrahepatic cholangiocarcinoma, associated resection, multiple concomitant LLR, redo resection, and lack of preoperative imaging. Anthropometric data were correlated with intraoperative outcomes.Forty-one patients (wedge resection, n = 32; segmentectomy, n = 9) were analyzed. A strong correlation was found between the craniocaudal liver diameter (CCliv) and liver volume (r = 0.655, p 0.001). The anteroposterior liver diameter was moderately correlated with both the laterolateral abdominal diameter (LLabd) (r = 0.372, p = 0.008) and anteroposterior abdominal diameter (r = 0.371, p = 0.008). The body mass index (BMI) was not correlated with liver diameters. Women had a longer CCliv (p = 0.002) and shorter LLabd (p 0.001) than men. The liver and abdominal measurements were combined to reduce this sex-related disparity. The CCliv/LLabd ratio (CHALLENGE index) was significantly correlated with the time of transection (r = 0.382, p = 0.037) and blood loss (r = 0.352, p = 0.029). The association between the CHALLENGE index and intraoperative blood loss was even stronger when considering only anatomical resection (r = 0.577, p = 0.048). A CHALLENGE index of 0.4 (area under the curve, 0.757; p = 0.046) indicated a higher bleeding risk. The BMI predicted no intraoperative outcomes.Anthropometric data rather than the BMI can help anticipate the difficulty of LLR of segments seven and eight.

It was speculated that intrahepatic cholangiocarcinoma (ICC) invasion would influence cancer progression, such as lymph node (LN) metastasis, and the efficacy of LN dissection (LND). The purpose of this study is to evaluate the LN metastatic pattern of intrahepatic cholangiocarcinoma, including the invasion category and prognosis after surgical resection, in order to explore effective LND. We analyzed a prospectively collected cohort for ICC with a previously reported invasion category: hilar type, showing invasion to the main or first branch of Glisson; peripheral type, showing no invasion to less than the third branch; and intermediate type, for all others. Data from a total of 180 patients who underwent surgical resection were analyzed (LN dissection in 142 (79%)). In single ICC, hilar type had a higher LN metastatic rate than the others (hilar; 23/45 (51%), intermediate; 7/25 (28%), peripheral; 1/34 (3%)). Although the survival with LN metastasis (LN+) was worse, single and hilar/intermediate ICC LN+ had a better survival than peripheral type LN+ (3-year OS: hilar/intermediate 30–37%, peripheral 0%). The most frequent LN metastatic region was the hepatico-duodenal ligament for all invasion categories, and the LN metastatic region was not related to the survival. In peripheral ICC, LND did not affect the survival. By contrast, hilar/intermediate ICC LN+ had a better survival than did peripheral ICC LN+, and the 3-year OS was ≥ 20%. LN metastasis depended on the ICC invasion category in addition to the tumor number, which affected patients’ survival and the need for LND. In hilar-type disease, LN dissection may contribute to the survival.

Liver and bile duct cancers are leading causes of worldwide cancer death. The most common ones are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Influencing factors and prognosis of HCC and ICC are different. Precise classification of these two liver cancers is essential for treatment and prevention plans. The aim of this study is to develop a machine-based method that differentiates between the two types of liver cancers from multi-phase abdominal computerized tomography (CT) scans. The proposed method consists of two major steps. In the first step, the liver is segmented from the original images using a convolutional neural network model, together with task-specific pre-processing and post-processing techniques. In the second step, by looking at the intensity histograms of the segmented images, we extract features from regions that are discriminating between HCC and ICC, and use them as an input for classification using support vector machine model. By testing on a dataset of labeled multi-phase CT scans provided by Maharaj Nakorn Chiang Mai Hospital, Thailand, we have obtained 88% in classification accuracy. Our proposed method has a great potential in helping radiologists diagnosing liver cancer.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common primary liver cancers. With the increasing incidence of ICC over the past two decades in Asia, it is essential to differentiate between HCC and ICC. However, ICC may mimic the radiological appearance of HCC on computed tomography scans (CT) and magnetic resonance imaging (MRI), leading to misdiagnosis of ICC. The objective of this study is to evaluate and describe the association of specific pre-operative imaging characteristics (arterial enhancement, portal venous washout) in patients with histologically proven resected ICC in our centre. Data on patients with histology-proven ICC and mixed hepatocellular-cholangiocarcinomas (HCC-CC) who had undergone surgical resection at Singapore General Hospital (SGH) were identified from a prospectively maintained database. Pre-operative cross-sectional imaging reports were analysed. Ninety-one patients underwent resection between 1 January 2000 and 31 December 2016. Among those with no risk factors for HCC, a significant percentage of patients with ICC (24.3%) show imaging characteristics of both arterial phase hyperenhancement and non-peripheral venous washout. Among patients with risk factors for HCC, between 20.0 and 33.3% of patients with pure ICC fulfilled the imaging criteria for HCC, and this proportion was generally even higher in the mixed HCC-CC group. A significant proportion of patients with pure ICC showed pre-operative imaging characteristics which fulfilled the diagnostic criteria for HCC. The differential of ICC should be borne in mind in populations where both malignancies are endemic.

Background: Y90 transarterial radioembolization (Y90-RE) may improve clinical outcomes of unresectable intrahepatic cholangiocarcinoma (ICC); however, the optimal timing for Y90-RE is still debated. The purpose of this multicenter study was to retrospectively evaluate clinical outcomes of RE in patients with unresectable ICC, comparing three different settings: chemotherapy naïve patients (group A), patients with disease control after first-line chemotherapy (group B) and patients with progression after first-line chemotherapy (group C). Materials and Methods: The study included 81 consecutive patients (49 male, mean age 62.4 ± 11.8years): 35 (43.2%) patients were in group A, 19 (23.5%) in group B, and 27 (33.3%) in group C. Preprocedural clinical variables, tumour response according to RECIST 1.1 and overall survival (OS) were analysed and compared. Results: Baseline demographic and clinical features did not differ significantly among groups, with the exception of prior surgical procedures that were significantly higher in group C patients, and macrovascular invasion that was more frequent in group B. Radiological response was available in 79 patients; objective response and disease control rates were 41.8% and 83.6%, respectively, without significant differences among groups. Median OS was 14.5months (95% CI: 11.1–16.9) and was not significantly different among treatment groups. At multivariate analysis, tumour burden > 50%, neutrophil-to-lymphocyte (N/L) ratio ≥ 3 and radiological progression as best response resulted to be significant (P < 0.05) independent factors, negatively associated with OS. Conclusion: Y90-RE is a valuable treatment option in unresectable ICC, irrespectively from the timing of treatment. Tumour extension, N/L ratio and radiological response affect post-treatment survival.

Primary hepatic carcinoma with inhibin positivity is a rare aggressive liver tumor with seven cases described. The tumor presents at a younger age than primary hepatic carcinoma with all cases being females. RNA albumin ISH positivity suggests the tumor to be a primary hepatic carcinoma. The tumor is different from hepatocellular carcinoma as well as intrahepatic cholangiocarcinoma because of its distinct morphology, lack of hepatocellular differentiation, strong inhibin staining, and lack of typical mutations. A 26-year-old male presented with a 20-cm liver mass. The tumor progressed on therapy with development of multiple lung metastasis. Currently, the patient is enrolled in phase II clinical trial utilizing nivolumab and ipilumumab. While the tumor has a female preponderance, it is not exclusively found in females. Additional studies are necessary to determine the cause of inhibin staining, driving molecular alterations, natural history of this rare tumor, and to come up with consensus nomenclature.

Intrahepatic cholangiocarcinoma is an aggressive malignancy with a poor prognosis. While the incidence and prevalence of intrahepatic cholangiocarcinoma are on the rise with each passing decade, more attention has paid to it. Radiologic examinations are an integral part of diagnosis and prognosis assessment of intrahepatic cholangiocarcinoma. In this article, we focus on the evaluation of CT and MRI in the diagnosis and prognosis of intrahepatic cholangiocarcinoma, highlighting the role of radiology in the prognosis.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary tract cancer (BTC) with distinct anatomic, molecular, and clinical characteristics that distinguishes it from other BTCs. In this landmark series review, we highlight the critical studies that have defined the surgical management of ICC, as well as several randomized controlled trials that have investigated adjuvant therapy strategies. Surgical resection is the mainstay of treatment and should involve margin-negative resection with regional lymphadenectomy. Several recently completed and ongoing randomized controlled trials are defining the indications for adjuvant therapy among patients with resected ICC. In the near future, improved understanding of the molecular features of ICC should lead to newer targeted therapies as well as a more personalized approach to systemic therapy.

To evaluate diagnostic values of the liver imaging reporting and data system (LI-RADS) M (LR-M) category based on novel explicit criteria that accept both targetoid and nontargetoid LR-M features and the suggested reporting algorithm of LI-RADS v2018 to assess primary liver cancers (PLCs) on gadoxetic acid-enhanced MRI (Gd-EOB-MRI). This retrospective study included 165 patients at high risk for hepatocellular carcinoma (HCC) with pathologically confirmed PLCs (HCC, n = 113; intrahepatic cholangiocarcinoma [iCCA], n = 23; and combined hepatocellular cholangiocarcinoma [cHCC-CCA], n = 29). Two radiologists independently analyzed Gd-EOB-MRI features and determined LI-RADS category for each tumor and categorized the likely etiology either as HCC or non-HCC malignancy if LR-M was assigned. Diagnostic performances for HCC or those for malignancy were compared according to imaging criteria. LR-M was assigned in 95.7%/91.3% of iCCAs; 55.2%/58.6% of cHCC-CCAs; and 21.2%/17.7% of HCCs in reviewers 1/2. Combination of LR-5 plus LR-M resulted in sensitivity of 95.2%/97.6% to diagnose PLCs as malignant, which were significantly higher than that of LR-5 plus “LR-M with ≥ 1 targetoid appearances” (84.8%/91.5%, Ps

Lymph node (LN) metastasis is one factor indicating a poor prognosis after radical surgery for intrahepatic cholangiocarcinoma (ICC). Although several guidelines have recommended that LN dissection be strongly considered at the time of ICC surgery, no clear evidence regarding the appropriate number of harvested LNs has been established. Thus, we aimed to identify the minimum number of harvested LNs required for ICC by using a Bayesian Weibull model. Data from 142 patients who underwent radical hepatectomy (R0) for ICC from January 2000 to December 2018 were retrospectively reviewed. A Bayesian Weibull model was developed to analyze the effect of number of harvested LNs on survival of patients without (N0; n = 71) and with (N1; n = 71) metastatic nodes. We also compared the percentage of N1 patients (i.e., the N1 rate) in each of the five subgroups categorized according to the number of harvested LNs (1–4, 5–8, 9–12, 13–16, and ≥ 17). In patients with 5 or more harvested LNs, the hazard ratio (HR) for LN metastasis was above the reference line (the HR with 5 harvested LNs, 1.95 (1.09–3.45)). The N1 rate of the 1–4 harvested LNs subgroup was lower than that of the other subgroups (e.g., 1–4 vs. 5–8; 16.1% vs. 39.4%, p = 0.014). Our results suggest that at least 5 LNs should be harvested in patients who undergo radical surgery for ICC to promote accurate staging.

Background: the aim of the present study is to analyze the outcomes of laparoscopic and open liver resections for (Intrahepatic CholangioCarcinoma) ICC in the modern era of laparoscopic liver surgery.Methods: patients undergoing laparoscopic and open liver resections for ICC in two European referral centers were included. Finally, 104 patients from the open group and 104 patients from the laparoscopic group were compared after propensity scores matching according to seven covariates representative of patients and disease characteristics. Indications to surgery and short- and long-term outcomes were compared.Results: operative time, number of retrieved nodes, rate, and depth of negative resection margins were comparable between the two groups. Blood loss was lower in the MILS (150 ± 100 mL, mean ± SD) compared with the Open group (350 ± 250 mL, p = 0.030). Postoperative complications occurred in 14.4% of patients in the MILS and in the 24% of patients in the Open group (p = 0.02). There were no significant differences in long-term outcomes between groups.Conclusions: our results confirm feasibility, safety, and oncological efficiency of the laparoscopic approach in the management of ICC. However, this surgery is often complex and should be only considered in centers with large experience in laparoscopic liver surgery.

The distinction between well-differentiated intrahepatic cholangiocarcinoma (iCCA) from its morphological mimics such as bile duct adenoma (BDA) and hamartoma (BDH) can be challenging, particularly in small biopsies. Although a few cases of BDA and BDH have been reported to undergo malignant transformation into iCCA, their neoplastic versus benign nature remains debated. DNA flow cytometry was performed on 47 formalin-fixed paraffin-embedded samples of iCCA, 14 BDA, and 18 BDH. Aneuploidy was detected in 22 iCCA (47%) but in none of the 32 BDA and BDH samples. Among the 34 iCCA patients who underwent complete resection and were followed up to tumor recurrence, tumor-related death, or at least for 1year, the overall recurrence or death rates (regardless of flow cytometric results) were 18, 56, and 71% within 1, 3, and 5years, respectively. The 1-, 3-, and 5-year recurrence or death rates in 18 iCCA patients with aneuploidy were 28, 66, and 66%, respectively, whereas 16 iCCA patients in the setting of normal DNA content had 1-, 3-, and 5-year rates of 6, 44, and 72%, respectively. Although aneuploid tumors were associated with worse outcomes during the first 3years, this difference was not statistically significant (hazard ratio = 1.4, p = 0.473) in the present sample size. In conclusion, the frequency of aneuploidy was significantly higher in iCCA (47%) than in its benign morphological mimics (0%), suggesting that it may potentially serve as a diagnostic marker of malignancy in challenging situations. Our findings also suggest that most BDAs and BDHs, if not all, are benign entities and may not represent precursor lesions to iCCAs that often harbor aneuploidy. Although a larger cohort will be necessary to further determine the prognostic significance of aneuploidy in iCCA patients after resection, the patients with aneuploid tumors may have a higher risk for tumor progression, especially during the first 3years.

Hemangiomas are the most common benign tumors of the liver. These lesions are typically asymptomatic, solitary and almost always discovered incidentally, and in recent years with advances in imaging technology these lesions are being detected more frequently. Although, in majority of the cases, the imaging diagnosis of a liver hemangioma is clearly and confidently established, not all hemangiomas present with their characteristic or typical appearance on imaging. Occasionally, these lesions do present with an atypical pattern, and can be confused with other malignant lesions such as hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma and angiosarcoma. In this article, we review with illustrations the diverse imaging appearances of hemangiomas on the commonly used imaging modalities, as well as provide a gamut of common and uncommonly encountered hemangioma mimickers. Knowledge of the various atypical avatars of this benign lesion is important and can help one circumvent diagnostic errors, thereby potentially avoiding unnecessary surgeries.

Background: The objective of the current study was to assess the impact of serum CA19-9 and CEA and their combination on survival among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). Methods: Patients who underwent curative-intent resection of ICC between 1990 and 2016 were identified using a multi-institutional database. Patients were categorized into four groups based on combinations of serum CA19-9 and CEA (low vs. high). Factors associated with 1-year mortality after hepatectomy were examined. Results: Among 588 patients, 5-year OS was considerably better among patients with low CA19-9/low CEA (54.5%) compared with low CA19-9/high CEA (14.6%), high CA19-9/low CEA (10.0%), or high CA19-9/high CEA (0%) (P < 0.001). No difference in 1-year OS existed between patients who had either high CA19-9 (high CA19-9/low CEA:70.4%) or high CEA levels (low CA19-9/high CEA:72.5%) (P = 0.92). Although patients with the most favorable tumor marker profile (low CA19-9/low CEA) had the best 1-year survival (87.9%), 15.1% (n = 39) still died within a year of surgery. Among patients with low CA19-9/low CEA, a high neutrophil-to-lymphocyte ratio (NLR) (odds ratio 1.09; 95% confidence interval 1.03-1.64) and large size tumor (odds ratio 3.34; 95% confidence interval 1.40–8.10) were associated with 1-year mortality (P < 0.05). Conclusions: Patients with either a high CA19-9 and/or high CEA had poor 1-year survival. High NLR and large tumor size were associated with a greater risk of 1-year mortality among patients with favorable tumor marker profile.

The AJCC made four changes to T category in the 8th AJCC stage for ICC, but this is a topic of debate. Data from 820 patients with ICC were extracted from the SEER database. Survival analysis of the 8th AJCC stage was examined. To verify the four T staging changes by survival analysis: prognosis of patients with tumor size > 5 cm was poorer than that with tumor size ≤ 5 cm (P

To compare the differences of MR features between mass-forming intrahepatic cholangiocarcinoma (IMCC) with and without lymph node metastasis (LNM) and to search for new imaging biomarkers for predicting LNM. The study included 91 patients with histopathologically confirmed single IMCC (20 patients with LNM and 71 patients without LNM). Findings of preoperative MR imaging including diffusion-weighted imaging (DWI) (b value 0, 500 mm2/s) were analyzed and apparent diffusion coefficient (ADC) values (b = 500 mm2/s) were calculated. Logistic regression analysis was performed to identify independent predictors of LNM. The diagnostic performance of independent predictors was assessed by receiver operating characteristic (ROC) and area under the curve (AUC) was compared. Larger tumor size (p = 0.001), diameter of largest lymph node (LN) > 1 cm (p 1 cm (odds ratio, 7.571; p = 0.004) were independent predictors of LNM. The AUCs for ADCIMCC value, diameter of largest LN > 1 cm,and combined method (the combination of ADCIMCC value and diameter of largest LN > 1 cm) were 0.782, 0.701,and 0.857, respectively. The AUC for combined method was significantly higher than that of diameter of largest LN > 1 cm (p = 0.033). ADCIMCC value can be a potential imaging biomarker for predicting LNM of IMCC, especially in combination with diameter of largest LN > 1 cm.

Based on recent advances in morphological and molecular research, tissue-based diagnostics of liver tumors exhibit a substantial dynamic. New clinically relevant tumor subtypes have been defined and the diagnostic criteria have been improved; examples are the new morphomolecular classifications of hepatocellular carcinoma and adenoma as well as intrahepatic cholangiocarcinoma. Therefore, molecular pathological diagnostics are gaining relevance in the identification of tumor types and therapeutic stratification. These developments are reflected in the new World Health Organization (WHO) classification of hepatobiliary tumors and the respective clinical practice guidelines.

The aim of this paper is to summarize the allocation challenges facing the field of liver transplantation while providing examples of the expansion of indications for the procedure. UNOS allocation policy was reviewed as well as the recent literature describing expanded criteria for recipient candidate selection. Liver allocation policy changes for deceased-donor organs remain gridlocked in legal and bureaucratic red tape. Meanwhile, the indications for liver transplantation are being expanded to include acute alcoholic hepatitis, intrahepatic cholangiocarcinoma, and colorectal metastasis, previously viewed as absolute contraindications, but under strict selection criteria. Attempting to meet the demand for livers, transplant centers are increasingly turning to living donor liver transplantation, protocols such as HCV-positive to HCV-negative transplants, and machine perfusion of marginal organs.

The aim of this study was to evaluate outcomes for patients with unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT). We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008 to 2018. Median age at RT was 76 years (range 30–92), including 27 patients (41%) aged ≥ 80 years. Median RT dose was 58.05 Gy (range 37.5–67.5), all delivered in 15 daily fractions. Thirty-two patients received proton RT and 34 patients received photon RT. Median follow-up times from diagnosis and RT start were 21 months and 14 months, respectively. In total, five patients (7.6%) developed local failure. The 2-year outcomes were 84% local control (LC) and 58% OS. Among the 51 patients treated with definitive intent, the 2-year LC rate was 93% and the OS rate was 62%. On multivariate analysis for LC, older age was associated with a lower risk of local failure [hazard ratio (HR) 0.91; p = 0.02], while prior surgery (HR 16.5; p = 0.04) and macrovascular invasion (HR 123.93; p = 0.02) were independently associated with an increased risk of local failure. On multivariate analysis for OS, female sex (HR 0.33; p = 0.001) and prior chemotherapy (HR 0.38; p = 0.003) remained significantly associated with OS. On multivariate analysis for OS, compared with photon RT, there was a trend towards improved survival with proton RT (HR 0.50; p = 0.05). The rate of overall grade 3 + toxicity was 11%. One patient developed radiation-induced liver disease and was treated with corticosteroids. HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent ICC.

Background Engineered versions of adeno-associated virus (AAV) are commonly used in gene therapy but evidence revealing a potential oncogenic role of natural AAV in hepatocellular carcinoma (HCC) has raised concerns. The frequency of potentially oncogenic integrations has been reported in only a few populations. AAV infection and host genome integration in another type of liver cancer, cholangiocarcinoma (CCA), has been studied only in one cohort. All reported oncogenic AAV integrations in HCC come from strains resembling the fully sequenced AAV2 and partly sequenced AAV13. When AAV integration occurs, only a fragment of the AAV genome is detectable in later DNA or RNA sequencing. The integrated fragment is typically from the 3’ end of the AAV genome, and this positional bias has been only partly explained. Three research groups searched for evidence of AAV integration in HCC RNAseq samples in the Cancer Genome Atlas (TCGA) but reported conflicting results. Results We collected and analyzed whole transcriptome and viral capture DNA sequencing in paired tumor and non-tumor samples from two liver cancer Asian cohorts from Thailand (N = 147, 47 HCC and 100 intrahepatic cholangiocarcinoma (iCCA)) and Mongolia (N = 70, all HCC). We found only one HCC patient with a potentially oncogenic integration of AAV, in contrast to higher frequency reported in European patients. There were no oncogenic AAV integrations in iCCA patients. AAV genomic segments are present preferentially in the non-tumor samples of Thai patients. By analyzing the AAV genome positions of oncogenic and non-oncogenic integrated fragments, we found that almost all the putative oncogenic integrations overlap the X gene, which is present and functional only in the strain AAV2 among all fully sequenced strains. This gene content difference could explain why putative oncogenic integrations from other AAV strains have not been reported. We resolved the discrepancies in previous analyses of AAV presence in TCGA HCC samples and extended it to CCA. There are 12 TCGA samples with an AAV segment and none are in Asian patients. AAV segments are present in preferentially in TCGA non-tumor samples, like what we observed in the Thai patients. Conclusions Our findings suggest a minimal AAV risk of hepatocarcinogenesis in Asian liver cancer patients. The partial genome presence and positional bias of AAV integrations into the human genome has complicated analysis of possible roles of AAV in liver cancer.