Small Intrahepatic Cholangiocarcinoma Research Articles

Clinicopathological features of cholangiolocarcinoma and impact of tumor heterogeneity on prognosis: A single institution retrospective study.

Cholangiolocarcinoma (CLC) is an extremely rare tumor classified as a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). There are few detailed reports on CLC and the prognostic impact of tumor heterogeneity is not clear. Between April 2006 and June 2022, of the 774 primary liver cancer resection cases who presented at Kanazawa University Hospital, 14 patients were pathologically diagnosed with CLC through immunohistochemical analysis of their molecular and biological features. Clinicopathological features and prognoses were evaluated retrospectively. Additionally, tumor heterogeneity was assessed and tumors were classified into pure and partial types according to the CLC component proportion in a single tumor. Chronic liver disease was observed in nine patients (64.3%). All tumors were mass-forming, and pathological R0 resection was achieved in 11 patients (78.6%). Tumor heterogeneity was classified as pure in 11 (78.6%) and partial in three (21.4%) patients. The median follow-up was 59.5 months (12-114 months). There was no difference in the 5-year disease-specific survival rates between the pure and partial (90.0% vs. 100.0%; P=0.200) types, but rates were significantly higher in the R0 resection group compared with those in the R1 resection group (100.0% vs. 50.0%; P=0.025). In conclusion, these results suggest that it is important for CLC patients to achieve curative resection, and CLC may have a good prognosis regardless of the proportion of CLC components in a single tumor.

Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear. This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies. Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group. Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs.

ASO Visual Abstract: Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma.

ASO Visual Abstract: Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma.

Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma.

Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry. Patients with clinical stage I-III ICC < 3 cm diagnosed 2010-2018 who underwent resection, ablation, or RT were identified in the National Cancer Database. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox proportional hazards methods. Of 545 patients, 297 (54.5%) underwent resection, 114 (20.9%) ablation, and 134 (24.6%) RT. Median OS was similar between resection and ablation [50.5 months, 95% confidence interval (CI) 37.5-73.9; 39.5 months, 95% CI 28.7-58.4, p = 0.14], both exceeding that of RT (20.9 months, 95% CI 14.1-28.3). RT patients had high rates of stage III disease (10.4% RT vs. 1.8% ablation vs. 11.8% resection, p < 0.001), but the lowest rates of chemotherapy utilization (9.0% RT vs. 15.8% ablation vs. 38.7% resection, p < 0.001). In multivariable analysis, resection and ablation were associated with reduced mortality compared with RT [hazard ratio (HR) 0.44, 95% CI 0.33-0.58 and HR 0.53, 95% CI 0.38-0.75, p < 0.001, respectively]. Resection and ablation were associated with improved survival in patients with ICC < 3 cm compared with RT. Acknowledging confounders, anatomic constraints of ablation, limitations of available data, and need for prospective study, these results favor ablation in small ICC where resection is not feasible.

Clinicopathological, etiological and molecular characteristics of intrahepatic cholangiocarcinoma subtypes classified by mucin production and immunohistochemical features

ABSTRACTBackgroundIntrahepatic cholangiocarcinoma (ICC) can be divided into two morphological subtypes: large duct type and small duct type ICC. This study aims to verify the feasibility of the classification criteria and clinicopathological characteristics of ICC.Research design and methodsICC patients were divided into the large and small type ICC by morphological and immunohistochemical patterns. Subsequently, clinicopathological data of the two groups was compared and the multivariate COX regression was used to verify the clinical significance of ICC subtypes. In addition, IDH1/2 mutation, KRAS mutation and FGFR2 translocation was also evaluated.ResultsTotally, 32, 61 and 13 tumors were defined as large, small and the indeterminate-duct type ICC respectively. Clinicopathologically, the large and small duct type ICC showed distinct morphological features. Compared with the small duct type ICC, the large duct type ICC had higher levels of serum tumor markers, vascular invasion, lymph node metastasis, and postoperative recurrence. Furthermore, positive FGFR2 rearrangement occurred only in small duct type ICC and IDH1/2 was mutated mainly in small duct type ICC.ConclusionsThe subclassification system was applicable and the ICC subtypes had distinct clinicopathological characteristics, prognostic outcome, and IDH1/2 mutation pattern.

Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study

Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype. Forty patients with surgically removed iCCA were prospectively enrolled: asbestos exposure was assessed according to the Italian National Mesothelioma Register questionnaire. From the surgical iCCA specimens the main histopathological variables were collected, including the small duct (sd-iCCA, 32 patients) and large duct subtypes (ld-iCCA, 8 patients). Five sd-iCCA cases had a definite/probable occupational exposure to asbestos, while no cases of ld-iCCA were classified as being occupationally exposed (definite/probable). Other kind of asbestos exposure (i.e. possible occupational, familial, environmental) were recorded in 16 sd-iCCA and 3 ld-iCCA. Cases with unlikely exposure to asbestos were 11 sd-iCCA (35.5%) and 5 ld-iCCA (62.5%). In conclusion, these findings seem to indicate that sd-iCCA might be more frequently associated to asbestos exposure rather than ld-iCCA, suggesting that asbestos fibres might represent a parenchymal, rather than a ductal risk factor for iCCA. This pilot study must be confirmed by further case–control studies or large independent cohorts.

Is nestin a diagnostic marker for combined hepatocellular–cholangiocarcinoma?

The type IV intermediate filament, nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Therefore, the significance of nestin as a diagnostic marker for cHCC-CCA categorized by the World Health Organization (WHO) 2019 classification and its relationship with clinicopathological features were examined in the present study. Nestin expression was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 22 with small duct-type intrahepatic cholangiocarcinoma (iCCA), 20 with large duct-type iCCA and 35 with hepatocellular carcinoma (HCC). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in cHCC-CCA. Nestin expression was detected in significantly more patients with cHCC-CCA (66.7%) than in those with large duct-type iCCA (5%) (P < 0.01), HCC (2.9%) (P < 0.01) and small duct-type iCCA (40.9%) (P < 0.05). Nestin expression was partly associated with neural cell adhesion molecule (NCAM) and vimentin expression. Nestin expression was also observed in significantly more patients with small duct-type iCCA than in those with large duct-type iCCA and HCC (P < 0.01). Nestin-positive cHCC-CCA was characterized by a smaller tumour size, the more frequent presence of cholangiolocellular carcinoma (CLC) components, a higher rate of p53 overexpression and a higher rate of multiple genetic alterations (P < 0.05). Furthermore, p53 overexpression was associated with a higher histological grade and multiple genetic alterations (P < 0.05) in nestin-positive cHCC-CCA. Nestin may be a useful diagnostic marker for a specific subgroup of cHCC-CCA and small duct-type iCCA associated with CLC components, p53 mutations and multiple genetic alterations, which are related to stemness and multipotent differentiation.

Apical Membrane Expression of Distinct Sulfated Glycans Is a Characteristic Feature of Ductules and Their Reactive and Neoplastic Counterparts.

Intrahepatic bile ducts transport bile between bile canaliculi and the extrahepatic bile duct. The luminal surface of this tract is lined by a layer of biliary epithelial cells, or cholangiocytes, which secrete mucins consisting of scaffold proteins and O-glycosidically linked carbohydrate side chains. Although mucin core proteins have been extensively investigated, the structure and function of carbohydrate side chains have not. Here, we demonstrate that distinct sulfated glycans positive for MECA-79, R-10G, and 297-11A, but not 5D4, monoclonal antibodies are expressed in the cytoplasm of cells of large-sized ducts and in the apical membrane of cells in ductules, and that R-10G immunolabeling is partially eliminated by endo-β-galactosidase digestion, supporting the presence of N-acetylglucosamine-6-O-sulfated N-acetyllactosamine structures. We observed comparable apical membrane-predominant staining in ductular reactions seen during regeneration that occurs in various liver diseases and in cholangiolocarcinoma, a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). Apical membrane expression of distinct sulfated glycans in large duct-type iCCA was negligible. Intriguingly, under pathological conditions, endo-β-galactosidase digestion almost completely eliminated R-10G immunoreactivity. These findings suggest that apical membrane expression of distinct sulfated glycans is a characteristic feature of ductules and their reactive and neoplastic counterparts.

Parenchyma-sparing hepatectomy improves salvageability and survival for solitary small intrahepatic cholangiocarcinoma

BackgroundThis study aimed to investigate the prognostic impact of parenchyma-sparing hepatectomy (PSH) on solitary small intrahepatic cholangiocarcinoma (ICC). MethodsA 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. Results95 (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). ConclusionPSH 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.

Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy and originates from the neoplastic transformation of the biliary cells. The intrahepatic subtype includes two morpho-molecular forms: large-duct type intrahepatic CCA (iCCA) and small-duct type iCCA. Iron is fundamental for the cellular processes, contributing in tumor development and progression. The aim of this study was to evaluate iron uptake, storage, and efflux proteins in both lipopolysaccharide-inflamed small and large cholangiocytes as well as in different iCCA subtypes. Our results show that, despite an increase in interleukin-6 production by both small and large cholangiocytes, ferroportin (Fpn) was decreased only in small cholangiocytes, whereas transferrin receptor-1 (TfR1) and ferritin (Ftn) did not show any change. Differently from in vitro models, Fpn expression was increased in malignant cholangiocytes of small-duct type iCCA in comparison to large-duct type iCCA and peritumoral tissues. TfR1, Ftn and hepcidin were enhanced, even if at different extent, in both malignant cholangiocytes in comparison to the surrounding samples. Lactoferrin was higher in large-duct type iCCA in respect to small-duct type iCCA and peritumoral tissues. These findings show a different iron handling by inflamed small and large cholangiocytes, and small and large-duct type iCCA. The difference in iron homeostasis by the iCCA subtypes may have implications for the tumor management.

Radiofrequency Ablation vs. Surgical Resection for Small Early-Stage Primary Intrahepatic Cholangiocarcinoma.

Aim: We aimed to compare the survival outcomes of radiofrequency ablation (RFA) and surgical resection (SR) for patients with small early-stage primary intrahepatic cholangiocarcinoma (ICC).Methods: Patients with small (≤5 cm) and early-stage ICC were screened from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) rates between the SR and RFA patients were evaluated. The results were verified using an inverse probability-weighting model (IPTW).Results: In total, 184 patients with small T1 stage ICC that received RFA or SR treatment were identified. The OS rates at 1, 3, and 5 years were 87.4, 73.3, and 61.5% for patients who underwent SR, respectively, and 89.9, 42.4, and 23.9%, respectively, for patients who received RFA. CSS rates at 1, 3, and 5 years were 91.5, 73.8, and 66.1%, respectively, for the SR group and 93.5, 53.4, and 30.0%, respectively, for the RFA group. The OS and CSS rates were evaluated to be significantly better in the SR group than in the RFA group after the multivariate Cox regression and IPTW analysis. Subsequently, the survival benefit of SR was also observed in the subgroup of patients with <4.5 or <4 cm early-stage ICC when compared with RFA.Conclusion: Our results indicated that the SR provided a significantly better prognosis than RFA in patients with small and early-stage ICC. SR as the first-line treatment of primary early-stage ICC is still recommended. However, prospective randomized controlled trials with larger sample sizes are required to compare these modalities in the treatment of ICC.

THU221 - Parenchyma-sparing hepatectomy improves salvageability and survival for solitary small intrahepatic cholangiocarcinoma

THU221 - Parenchyma-sparing hepatectomy improves salvageability and survival for solitary small intrahepatic cholangiocarcinoma

Analysis of Liver Resection Versus Liver Transplantation on Outcome of Small Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma in the Setting of Cirrhosis.

This multicenter study compares the outcomes of patients with cirrhosis undergoing liver transplantation (LT) or liver resection (LR) between January 2002 and July 2015 who had intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA) found incidentally in the native liver. A total of 49 (65%) LT and 26 (35%) LR patients with cirrhosis and histologically confirmed iCCA/cHCC-CCA ≤5cm were retrospectively analyzed. LT patients had significantly lower tumor recurrence (18% versus 46%; P=0.01), for which the median diameter of the largest nodule (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12]; P=0.006) and tumor differentiation (HR, 3.74; 95% CI 1.71-8.17; P=0.001) were independently predictive. The LT group had significantly higher 5-year recurrence-free survival (RFS; 75% versus 36%; P=0.004). In patients with tumors >2cm but ≤5cm, LT patients had a lower recurrence rate (21% versus 48%; P=0.06) and a higher 5-year RFS (74% versus 40%; P=0.06). Independent risk factors for recurrence were LT (protective; HR, 0.23; 95% CI, 0.07-0.82; P=0.02), the median diameter of the largest nodule (HR, 1.10; 95% CI, 1.02-1.73; P=0.007), and tumor differentiation (HR, 4.16; 95% CI, 1.37-12.66; P=0.01). In the LT group, 5-year survival reached 69% and 65% (P=0.40) in patients with tumors ≤2cm and >2-5cm, respectively, and survival was also comparable between iCCA and cHCC-CCA patients (P=0.29). LT may offer a benefit for highly selected patients with cirrhosis and unresectable iCCA/cHCC-CCA having tumors ≤5cm. Efforts should be made to evaluate tumor differentiation, and these results need to be confirmed prospectively in a larger population.

The landscape of predictive biomarkers for ATR inhibition in Chinese solid-tumor patients.

3626 Background: Ataxia Telangiectasia and Rad3-related (ATR) is one of the core regulators participating in DNA damage response as a sensor of replication stress. Besides, ATR also plays a role in cell cycle checkpoint activation and DNA replication regulation. Several ATR inhibitors (ATRi) have been demonstrated in anti-cancer clinical trials. Herein, we describe the distribution of selected biomarkers, which have been shown to predict a higher sensitivity to ATRi according to preclinical data, in Chinese cancer population. Methods: FFPE tumor tissues and matched blood samples from 10,194 Chinese patients with 25 different types of solid tumors were collected. NGS based 450 cancer genes panel assay were performed to detect genomic alterations, including SNV, short and long insertions/deletions, CNV and rearrangements/fusions. The testing was carried out by a CAP accredited and CLIA certified laboratory. Results: The prevalence of ARID1A mutations, ATM mutations, BRCA1/BRCA2 mutations, MYC amplification, and CCNE1 amplification accounted for 9.5%, 4.7%, 6.0%, 3.5% and 3.3% of this cohort respectively. The most common tumors with ARID1A mutations were endometrial carcinoma (EC, 34.4%), gastric carcinoma (GC, 19.4%), small bowel carcinoma (SBC, 19.3%), intrahepatic cholangiocarcinoma (19.3%), extrahepatic cholangiocarcinoma (17.7%) and urothelial carcinoma (UC, 16.7%). For ATM mutations, the prevalence was colorectal carcinoma (CRC, 8.9%), SBC (8.8%), pancreatic cancer (7.8%), UC (7.3%), gallbladder carcinoma (GBC, 7.1%) and GC (6.8%). For BRCA1/BRCA2 mutations, the prevalence was ovarian carcinoma (29.5%, Germline 23%), breast carcinoma (13.3%, Germline 7.1%), EC (11.5%, Germline 3.3%), UC (10.4%), melanoma (8.5%) and CRC (7.9%). For MYC amplification, the prevalence was breast carcinoma (10.2%), ovarian carcinoma (9.2%), esophageal carcinoma (7.2%), thymic tumor (6.1%), cancer of unknown primary (CUP, 5.8%) and gastrointestinal neuroendocrine tumor (GI-NET, 5.4%). For CCNE1 amplification, the prevalence was GC (11.9%), GBC (8.8%), bone sarcoma (7.7%), ovarian carcinoma (6.9%), CUP (4.2%) and GI-NET (4.1%). Conclusions: Our study reported the prevalence of gene mutations of ATRi sensitivity determinants in a large cohort of Chinese cancer patients. The results revealed the high prevalence and different distribution of these biomarkers across a wide spectrum of cancers. The genomic profile study also provided information for ATRi sensitivity assessment and the drug combinations with ATR inhibition.

Comparison of the Clinicopathological Features and Survival in Small Bile Duct Type and Bile Ductular Type Intrahepatic Cholangiocarcinoma

Background: Intrahepatic cholangiocarcinoma (ICC) is anatomically divided into the perihilar subtype and the peripheral subtype. Peripheral ICC can be further classified into the small bile duct type and bile ductular type based on the pathological findings.The small bile duct type was considered to have the nature of conventional ICC, such as tubular and micropapillary carcinoma with desmoplastic variation and this may have different features from the bile ductular type characterized by bile ductular features with slit-like lumen. However, the differentiation of the clinicopathological features between small bile duct and bile ductular type ICC, which were anatomically categorized as the same peripheral type, has not been well defined.

Arterial hyperenhancement of small intrahepatic cholangiocarcinomas correlates with microvessel counts and patient survival

BackgroundTo compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. MethodsFrom June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast–enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. ResultsThe median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. ConclusionThe presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy.

Potential survival benefit of radiofrequency ablation for small solitary intrahepatic cholangiocarcinoma in nonsurgically managed patients: A population-based analysis.

Little data regarding the selection of nonsurgical therapies for localized intrahepatic cholangiocarcinoma (ICC) are available. A cohort of nonsurgically managed patients with American Joint Commission on Cancer clinical stage I/II ICC in the United States from 2004 to 2013 were identified in the National Cancer Database. Overall survival (OS) was compared according to treatment options (radiofrequency ablation [RFA] vs chemoradiotherapy) using propensity-score matching. Among 505 patients, 86 patients were treated with RFA and 419 patients were treated with chemoradiotherapy. After propensity matching (n = 84, each group), 5-year OS was 17.6% among patients who underwent RFA vs 3.8% among patients receiving chemoradiotherapy (P < .001). On bivariate analysis, RFA was related to an OS benefit (hazard ratio, 0.46; 95% confidence interval, 0.33-0.66; P < .001). Specifially, a stage-specific subgroup analysis revealed a survival benefit in favor of RFA among stage I patients (5-year OS; RFA: 20.1% vs chemoradiotherapy: 3.7%, P < .001), whereas no difference in OS was noted among patients with stage II disease. Among ICC patients with small (≤5 cm), solitary ICC without vascular invasion, RFA was associated with better survival compared with chemoradiotherapy.

Role of Lymph Node Dissection in Small (≤ 3 cm) Intrahepatic Cholangiocarcinoma

Background and AimsThe role of lymph node dissection (LND) in patients with small intrahepatic cholangiocarcinoma (ICC) is still under debate.The aims of this study were to compare the lymph node (LN) status and its correlation with survival among patients with ICC stratified by tumor size. MethodsA retrospective analysis of a multi-institutional series of 259 patients undergoing curative-intent surgery was carried out. Patients were stratified into Small-ICC (≤ 3 cm) and Large-ICC (> 3 cm) based on tumor size. ResultsThere were 53 and 206 patients in Small-ICC and Large-ICC groups, respectively. The incidence of LND was 62% among Small-ICC patients and 78% among Large-ICC patients (p = 0.016). LN metastases were identified in 30.3% and 38.5% of Small-ICC and Large-ICC patients, respectively (p = 0.37). No differences in terms of number of harvested LN and LN metastases were identified comparing Small- and Large-ICC patients. The 5-year overall survival (OS) was 52.6% for Small-ICC and 36.2% for Large-ICC (p = 0.024). The 5-year OS according to the LN status (N0 vs N+) was 84.8% and 36.0% (p = 0.032) in Small-ICC, and 45.7% and 12.1% in Large-ICC (p < 0.001), respectively. ConclusionWhile Small-ICC patients with no LN metastasis had a good long-term survival, the LN resulted in an important variable associated with survival also for patients in this group. Moreover, the incidence of LN metastasis did not differ when comparing Small-ICC and Large-ICC patients, suggesting that LND is mandatory in the surgical treatment of ICC regardless of tumor size.

Role of lymph-node dissection in small (≤ 3cm) intrahepatic cholangiocarcinoma

Role of lymph-node dissection in small (≤ 3cm) intrahepatic cholangiocarcinoma

Locoregional Therapy With Transarterial Chemoembolization (TACE) for Stage 1A Intrahepatic Cholangiocarcinoma (ICC) Before Surgical Resection: A Case Report

Intrahepatic cholangiocarcinoma is usually treated by hepatic resection to achieve negative resection margins but only minority of patients present with early stage disease. Hepatic artery based therapies such as radioembolization (TACE) is used for locally advanced unresectable disease. We present a case of stage 1A localized ICC treated with TACE followed by radiotherapy with possible liver resection in the future. A 42 year old male with history of alcohol use disorder, diabetes mellitus and hypertension came in with right upper quadrant abdominal pain. Abdominal examination was significant for distended abdomen with epigastric tenderness. Labs revealed alanine transaminase (ALT) 72 U/L, aspartate transaminase (AST) 79 U/L, platelet count 132 k/uL, and INR of 1.0. He had a sonogram of the liver which revealed a complex left hepatic lobe lesion with peripheral vascularity, so magnetic resonance imaging (MRI) of abdomen was done which showed cirrhosis with portal hypertension and 2.6 x 2.3 cm lesion involving segment II and III (Figure 1). His viral hepatitis panel was negative, and CA 19-9 was 36.8 U/ml. He underwent EGD and colonoscopy which revealed no mass. Interventional radiology (IR) guided liver biopsy of mass ICC. Patient underwent IR guided TACE with 75 mg of Doxorubicin beads administered into segmental branch of right hepatic artery the tumor (Figure 2) followed by split beam radiation therapy (SBRT). Repeat CT scan of abdomen done 7 months post TACE has not shown recurrent disease (Figure 3).2328_A Figure 1. MRI abdomen showing 2.6 x 2.3 cm lesion involving segment II and III of liver (red arrow) before TACE procedure2328_B Figure 2. Cone beam CT imaging (right) during TACE procedure showing chemotherapy beads being administered near tumor site by catheter (red arrow) & contrast enhancement of tumor site (left) on digital subtraction angiography (DSA) imaging.2328_C Figure 3. CT abdomen showing post treatment tumor with surrounding peripheral region of hyper density representing post TACE changes (red arrow).Intrahepatic tumors derive blood supply from hepatic artery rather than portal vein. This has led to development of TACE which involves elimination of tumor's blood supply by particle embolization and/or cytotoxic chemotherapy infusion into the branch of hepatic artery that feeds the tumor. Such therapies, particularly radioembolization, appear promising for patients with locally advanced unresectable ICC. Partial hepatectomy is the treatment of choice for small peripheral ICC. In our case due to patient's current heavy alcohol use and compensated cirrhosis, partial hepatectomy was thought to confer a very high risk for hepatic decompensation postoperatively. So, he was successfully treated with TACE followed by radiotherapy, with plan of left hepatic resection once he is abstinent from alcohol. Our case demonstrates the effectiveness of TACE for ICC which cannot undergo partial liver resection due to his alcoholic cirrhosis.