Efficacy and Safety of Sorafenib in Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

INTRODUCTION: Because the frequency of bile duct invasion in hepatocellular carcinoma (HCC) patients is very rare, there is limited clinical evidence to demonstrate the outcomes of systemic therapy in HCC with bile duct invasion. OBJECTIVE: Our aim was to clarify the efficacy and safety of sorafenib treatment in patients with unresectable advanced HCC with bile duct invasion. METHODS: One hundred and seventy-five patients with advanced HCC were enrolled in this study. We retrospectively compared the outcomes of sorafenib between patients without bile duct invasion [B (-) group, n = 165] and those with bile duct invasion [B (+) group, n = 10]. RESULTS: There were no significant differences in the confirmed objective response rate (ORR) and the confirmed disease control (DC) rate between the B (-) and the B (+) groups (13.9 vs. 20.0%, p = 0.637 for ORR; 47.2 vs. 70.0%, p = 0.202 for DC rate, respectively). There were no significant differences in median overall survival (OS) and time to progression (TTP) between the B (-) group and the B (+) group (14.8 vs. 14.1 months, p = 0.780 for OS; 3.4 vs. 5.7 months, p = 0.277 for TTP, respectively). Post-treatment factors associated with good OS were changes in albumin-bilirubin score (0-6 weeks) of <0.25, and antitumor response at 6 weeks of DC. Though 5 of 10 patients (50%) in the B (+) group had bile duct complications, such as obstructive jaundice and biliary bleeding, these 5 patients were able to recover from biliary troubles by careful and vigorous management with biliary endoscopic intervention, and were able to continue sorafenib therapy safely. CONCLUSIONS: Our present results suggest that sorafenib might have potential therapeutic efficacy and safety in advanced HCC patients with bile duct invasion. In case of biliary tract troubles before and during sorafenib treatment, early biliary management may be important to continue sorafenib therapy safely. Further studies are needed to confirm the outcomes of sorafenib in advanced HCC patients with bile duct invasion.

Lower bile duct metastasis from rectal cancer after surgery for liver metastasis and intrahepatic bile duct metastasis: a case report.

BACKGROUND: Biliary metastasis of colorectal cancer is a manifestation of metastatic liver carcinoma, and is often difficult to differentiate from cholangiocarcinoma. Further, lower bile duct metastasis of colorectal cancer is rare. We report the case of a 74-year-old woman who underwent pylorus-preserving pancreatoduodenectomy for lower bile duct metastasis of rectal cancer. CASE PRESENTATION: The patient had undergone laparoscopic low anterior resection for rectal cancer (pT3N0M0 stage IIA) 6 years ago, laparoscopic anterior liver resection for liver metastasis (Couinaud segment V) 3 years ago, and left and caudal lobectomy with extrahepatic bile duct resection for left intrahepatic bile duct metastasis 6 months ago. A follow-up examination showed a 15 mm mass in the common bile duct, for which she underwent pylorus-preserving pancreatoduodenectomy. Histological and immunohistological examination of the specimens revealed similar cytokeratin (CK) expression patterns, which were negative for CK7 and positive for CK20. Therefore, the definitive diagnosis was metastasis from rectal cancer. CONCLUSIONS: In summary, we encountered a case of lower bile duct metastasis from rectal cancer, which is often difficult to differentiate from cholangiocarcinoma. In such patients, CK7 and CK20 expression patterns are important in differentiating the two. The mechanism of metastasis in this case was considered to be through cancer cell implantation from lymphatic spread, or through distant metastasis of the primary cancer.

S100A11 promotes cell proliferation via P38/MAPK signaling pathway in intrahepatic cholangiocarcinoma.

S100A11 is reported to associate with progression and poor prognosis in several tumors. We previously reported that S100A11 was highly expressed in intrahepatic cholangiocarcinoma (ICC) cells and promoted TGF-ß1-induced EMT through SMAD2/3 signaling pathway. Here, we explored the prognostic role of S100A11 on ICC patients and preliminary molecular mechanisms how S100A11 regulated ICC cell proliferation. Our results showed that S100A11 was obviously increased in ICC tumor tissues. High expression of S100A11 was closely correlated with lymph node metastasis (LNM) and TNM stage and was an independent risk factor for patients' overall survival (OS) and recurrence-free survival (RFS). The nomograms comprising LNM and S100A11 achieved better predictive accuracy compared with TNM staging system for OS and RFS prediction. Silencing S100A11 significantly suppressed RBE cells and HCCC9810 cells proliferation, colony formation, and activation of P38/mitogen-activated protein kinase (MAPK) signaling pathway in vitro and inhibited tumor growth in vivo. In contrast, the overexpression of S100A11 in RBE cells and HCCC9810 cells achieved the opposite results. S100A11-induced proliferation was abolished after treatment with P38 inhibitor. Our findings suggest S100A11/P38/MAPK signaling pathway may be a potential therapeutic target for ICC patients.

Therapeutic Index Associated with Lymphadenectomy Among Patients with Intrahepatic Cholangiocarcinoma: Which Patients Benefit the Most from Nodal Evaluation?

BACKGROUND: Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear. METHODS: Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup. RESULTS: Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)]. CONCLUSION: The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM.

Intrabiliary growth type of metastasis from colon cancer, 12 years after curative colectomy: a case report.

BACKGROUND: Liver is a common location of colorectal metastasis, but intrabiliary growth of liver metastasis is not well recognized. Furthermore, intrabiliary metastasis that discovered over 10 years after excision has rarely been described. CASE PRESENTATION: An 80-year-old man was admitted due to the presence of a liver mass in segment 5 (S5) concomitant with elevated carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9. He underwent right hemicolectomy for colon cancer 12 years prior. Enhanced computed tomography (CT) showed dilated bile ducts with periductal enhancement in S5; hence, cholangiocarcinoma was suspected. Upon anterior segmentectomy, we observed that the cut surface of the specimen exhibited a yellowish-white tumor within the bile ducts. Histologically, the tumor formed within the papillary process, extended along the lumen, and replaced the normal bile duct epithelium. Immunohistochemical studies showed that the liver tumor and primary colon cancer were negative for cytokeratin (CK) 7 and positive for CK20 and Caudal-type homeobox transcription factor 2 (CDX-2). In addition, both tumors showed a same KRAS mutation. We diagnosed the liver tumor as liver metastasis recurrence from colon cancer. CONCLUSION: Intrabiliary growth type of metastasis (IGM) is difficult to distinguish from cholangiocarcinoma, and sometimes develops long after surgery; thus, careful examination of a patient's history is needed in such cases.

Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis.

BACKGROUND: The objective of this meta-analysis was to evaluate the effectiveness and safety of lymph node dissection (LND) in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: A literature search with a date range of January 2000 to January 2018 was performed to identify studies comparing lymph node dissection (LND+) with non-lymph node dissection (LND-) for patients with ICC. The LND + group was further divided into positive (LND + N+) and negative (LND + N-) lymph node status groups based on pathological analysis. RESULTS: 13 studies including 1377 patients were eligible. There were no significant differences in overall survival (OS) (HR 1.13, 95% CI 0.94-1.36; P = 0.20), disease-free survival (DFS) (HR 1.23, 95% CI 0.94-1.60; P = 0.13), or recurrence (OR 1.39, 95% CI 0.90-2.15; P = 0.14) between LND + group and LND-group. Postoperative morbidity was significantly higher in the LND + group (OR 2.67, 95% CI 1.74-4.10; P < 0.001). A subset analysis showed that OS was similar between LND + N- and LND-groups (HR 1.13, 95% CI 0.82-1.56; P = 0.450). However when comparing, OS of the LND-group to the LND+N+ group there was a significant increase in OS for the LND-group (HR 3.26, 95% CI 1.85-5.76; P < 0.001). CONCLUSIONS: LND does not seem to positively affect overall survival and is associated with increased post-operative morbidity.

[Curative Resection for Liver Metastasis Ten Years after Surgery for Rectosigmoid Cancer-A Case Report].

Here, we report the case of a 73-year-oldfemale patient, who previously underwent high anterior resection for rectosigmoidcancer at the age of 63. Her scheduled5 years of follow-up after colorectal surgery hadbeen finished, but she kept undergoing endoscopic mucosal resection for colorectal polyps every 1 or 2 years since then. Blood examination 10 years 6 months after surgery for rectosigmoidcancer revealedthat the value of her serum CEA was 5.5 ng/mL, which was slightly higher than the normal range. Contrast-enhancedCT showedan irregular-shapedtumor with a diameter of 3 cm in which the contrast of the peripheral area was mainly emphasized. When combining the results of MRI and PET-CT examinations, the liver tumor was clinically diagnosed as either intrahepatic cholangiocarcinoma or metastatic liver cancer. Since the first choice of therapy was tumor resection for both diagnoses, S8 subsegmental hepatectomy was performed 10 years 8 months after surgery for rectosigmoidcancer. HE staining of the resectedspecimen showedwell or moderately differentiatedad enocarcinoma, andits immunostaining findings were as follows: CDX-2: positive, CK20: positive, CK7: negative. It was pathologically diagnosed as liver metastasis from rectal cancer. It is rare for colorectal cancer to have metachronous liver metastasis more than 10 years after surgery. However, in any case where a tumor marker for colorectal cancer increases, it is necessary to examine carefully with the possibility of any metastasis in mind.

Chemoembolisation for hepatocellular carcinoma with bile duct invasion: is preprocedural biliary drainage mandatory?

PURPOSE: To determine the necessity of preprocedural biliary drainage prior to chemoembolisation for hepatocellular carcinoma (HCC) with bile duct invasion. MATERIALS AND METHODS: The study included 52 patients who received chemoembolisation for unresectable HCC invading bile duct and causing hyperbilirubinemia (>3 mg/dL). Patients were divided into three groups according to biliary drainage and its effect: effective drainage (n=21), ineffective drainage (n=17), and non-drainage (n=14). Thirty-day mortality, length of hospitalisation, adverse events recorded using Common Terminology Criteria for Adverse Events (CTCAE), survival, and tumour response was compared among three groups. RESULTS: Thirty-day mortality rates were 14.3% (n=3), 17.6% (n=3), and 7.1% (n=1) for effective, ineffective, and non-drainage groups, respectively, and did not differ significantly among groups (p=0.780). The mean length of hospitalisation was shorter in non-drainage group compared to ineffective drainage group (12.1±11.4 vs 34.1±29.6 days, p=0.012). Mean differences in CTCAE grade for laboratory parameters before and after chemoembolisation were not significantly different among three groups. Survival among three groups was not significantly different (p=0.239-0.825). The tumour response was also not significantly different among three groups (p=0.679). CONCLUSION: Biliary drainage may not be mandatory prior to chemoembolisation in patients with HCC invading the bile duct. KEY POINTS: • Chemoembolisation without biliary drainage can be performed for icteric HCC. • Chemoembolisation without biliary drainage is not accompanied by increased adverse events. • Preprocedural biliary drainage may not be mandatory for chemoembolisation for icteric HCC.

Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden.

BACKGROUND: Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. METHODS: Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. RESULTS: A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. CONCLUSION: The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies.

[Intrahepatic Bile Duct Metastasis from Rectal Adenocarcinoma Eight Years after Curative Operation].

A 60-year-old male undergoing pelvic evisceration with D3 lymph node dissection for pR0 in 2006f or carcinoma of the rectum was diagnosed pathologically with moderately differentiated adenocarcinoma, fStage ⅡA(UICC pT3, pN0, M0). Follow-up CT revealed hypovascular liver tumors with intrahepatic bile duct dilation in the right lobe 8 years after the pelvic evisceration. We conducted right lobe hepatectomy. The resected specimens showed that the tumor extended predominantly along the right intrahepatic bile duct. Histological findings and an immunohistochemical examination of CK7, CK20, and CDX2 revealed metastasis of the rectum cancer. We finally diagnosed him with intrahepatic bile duct metastasis from rectal adenocarcinoma.

[Comparative analysis of side-by-side antegrade stenting and Y-biliary stenting for malignant biliary stricture]. / Sravnitel'nyi analiz antegradnogo stentirovaniia side-by-side i Y-stentirovaniia pri zlokachestvennoi zhelchnoi strikture vorot pecheni.

In the time period from 2009 to 2017 in Botkin Hospital (Moscow) bilateral biliary stenting was performed in 43 patients with malignant common hepatic duct stricture. Patients were divided into 2 statistically homogeneous groups: 'side-by-side' stenting in 28 patients and percutaneous 'Y'-biliary stent placement in 15 patients. The causes of malignant obstruction were as follows: in the 1st group 13 (46.4%) patients with extrahepatic cholangiocarcinoma (46.4%), 8 (28.6%) patients with intrahepatic cholangiocarcinoma, 4 (14.3%) patients with gallbladder cancer, 3 (10.7%) patients with metastatic cancer. In the 2nd group 6 (40%) patients with extrahepatic cholangiocarcinoma, 4 (26.6%) patients with intrahepatic cholangiocarcinoma, 2 (13.3%) patients with gallbladder cancer, 3 (20%) patients with metastatic cancer. Characteristics of patients: age - 1st group 71.2±5.1 years, 2nd group 74.3±5.5 years; sex - (m/f) 1st group 18/10, 2nd group 9/6; location of stricture - 1st group Bismuth IIIa/IIIb 17/11, 2nd group Bismuth IIIa/IIIb 11/4; mean level of bilirubin - 1st group 284±8.2 µmol/l; 2nd group 311±7.4 µmol/l. Technically all procedures were successful (100%). No complications and mortality associated with the procedure was recorded. Clinically significant results were achieved in 26 (92.8%) patients in Group 1 and in 13 (86.7%) patients in Group 2 (p=0.043). Following stenting procedures, 23 (82.1%) patients in Group 1 and 11 (68.8%) patients in the Group 2 had chemotherapy (p=0.047). 19 patients from the 1st group and 10 patients from the 2nd group died due to tumor progression of the underlying disease, other patients are under care of a physician. Median survival rate: 1st group (12 patients - 50 days, 7 patients - 100 days, 9 patients are alive at the time of writing); 2nd group (7 patients - 50 days, 4 patients - 100 days, 4 patients are alive at the time of writing). The results of this study showed that 6 (21.4%) patients from the 1st group and 4 (26.7%) patients from the 2nd group had biliary stent occlusion (p=0.041). The average period of stent function in the 1st group was 78±4.5 days, and 63±4.8 days in the 2nd group (p=0.036). Based on the obtained results, it is recommended to use the 'side-by-side' method of bilobar biliary stenting in patients with malignant common hepatic duct strictures.

Paraneoplastic pityriasis rubra pilaris: case report and literature review.

Pityriasis rubra pilaris (PRP; MIM 173200) is an uncommon papulosquamous inflammatory dermatosis. Only a few cases of PRP associated with an underlying malignancy have been documented. We investigated a 59-year-old patient presenting with a fulminant form of PRP recalcitrant to systemic retinoid therapy, in whom the skin disease heralded a diagnosis of cholangiocarcinoma. We searched the MEDLINE database to find articles reporting on similar associations of PRP with malignancies. We identified 10 studies linking PRP and malignancies, but an association between PRP and cholangiocarcinoma has not yet been reported.

Bullous Pemphigoid as a Harbinger of Metastatic Cholangiocarcinoma - A Rarity.

Bullous pemphigoid (BP) is an autoimmune blistering disorder of the skin first described in 1953. A decade later, antibodies were described targeting the cutaneous basement membrane zone. The association of Bullous pemphigoid with malignancy is debatable1 but reported in many case reports.2-6 We report a 79 year old male with cholangiocarcinoma that presented with bullous pemphigoid as a paraneoplastic phenomenon.

Prognostic Accuracy of the Seventh Edition of the TNM Classification Compared with the Fifth and Sixth Edition for Distal Cholangiocarcinoma.

BACKGROUND: The TNM classification for distal cholangiocarcinoma was first introduced in the 7th edition, which was published in 2009; however, prognostic accuracy compared with the 5th and 6th editions has not yet been evaluated and requires validation. METHODS: A prospective histological database of patients with distal bile duct cancer was analyzed, and histological parameters and stage of the distal cholangiocarcinoma were assessed according to the 5th, 6th, and 7th editions of the TNM classification. RESULTS: Between 1994 and 2012, a total of 516 patients underwent pancreatic head resection, of whom 59 patients (11.4 %) experienced histologically confirmed distal cholangiocarcinoma. The median overall survival time was 22.2 months (13.1-31.4). Tumor recurrence occurred in 23 patients after a median disease-free survival time of 14.1 months. The 7th edition showed a monotonicity of all gradients, with a stepwise increase of mortality related to a stepwise increase of tumor stage (log-rank test; p < 0.05) demonstrating best discrimination of all tested editions [area under the receiver operating characteristic curve (AUC) 0.82; 95 % CI 0.70-0.95; p = 0.012]. The discrimination rate was low for the 5th (AUC 0.67; 95 % CI 0.42-0.91; p = 0.18) and 6th editions (AUC 0.70; 95 % CI 0.47-0.93; p = 0.11), while the log-rank test did not reach statistical significance. On multivariate analysis, lymph node involvement and positive resection margins were positive and independent predictors of inferior survival (p < 0.05). CONCLUSIONS: The 7th edition of the TNM classification was favorable in terms of predicting outcome, and generated a monotonicity of all grades. Strikingly, the 7th edition, but not the 5th and 6th editions, was of prognostic significance to predict outcome.

Biliary intraductal metastasis from advanced gastric cancer: radiologic and histologic characteristics, and clinical outcomes of percutaneous metallic stent placement.

OBJECTIVES: To investigate the radiologic and histological characteristics of biliary intraductal metastasis of advanced gastric cancer and the clinical outcomes of percutaneous, metallic stent placement. MATERIALS AND METHODS: We retrospectively assessed 24 patients with obstructive jaundice related to biliary intraductal metastasis of gastric cancers who underwent PTBD and subsequent metallic stent placement between 2003 and 2012. RESULTS: Intraductal metastases appeared as uniform, concentric, linear (n = 17) or band-like (n = 7), enhanced wall thickening on CT, and 20 patients (83.3 %) had cystic ductal lesions. On pathology specimens, malignant cells scattered in the submucosal layer caused a desmoplastic reaction. The technical and clinical success rate of stent placement was achieved in all 24 patients. The median survival time was 203 days. Stent occlusion was observed in four patients with 49-278 days following stent placement. The median stent patency time was 156 days. CONCLUSIONS: The radiologic and histological characteristics of biliary intraductal metastasis of advanced gastric cancer consist of uniform, linear or band-like, enhanced biliary wall thickening and malignant cells scattered in the submucosal layer, together with the desmoplastic reaction without any disruption of the epithelial layer. Uncovered metallic stent placement was also a safe and effective method of palliative treatment in these patients. KEY POINTS: • The CT findings of intraductal metastasis were linear/band-like, enhanced biliary wall thickening. • The histological finding was malignant cells scattered in the submucosal layer. • It showed a desmoplastic reaction without any disruption of the epithelial layer. • Uncovered metallic stent placement was a safe and effective palliative treatment.

Diagnostic accuracy of staging laparoscopy for detecting metastasized or locally advanced perihilar cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Despite extensive preoperative staging, still almost half of patients with potentially resectable perihilar cholangiocarcinoma (PHC) have locally advanced or metastasized disease upon exploratory laparotomy. The value of routine staging laparoscopy (SL) in these patients remains unclear with varying results reported in the literature. The aim of the present systematic review was to provide an overview of studies on SL in PHC and to define its current role in preoperative staging. METHODS: A systematic review and meta-analysis were performed in PubMed and EMBASE regarding studies providing data on the diagnostic accuracy of SL in PHC. Primary outcome measures were the overall yield and sensitivity to detect unresectable disease. Secondary outcomes were the yield and sensitivity for recent studies (after 2010) and large study cohorts (≥100 patients) and specific (metastatic) lesions. Methodological quality of studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: From 173 records, 12 studies including 832 patients met the inclusion criteria. The yield of SL in PHC varied from 6.4 to 45.0 % with a pooled yield of 24.4 % [95 % confidence interval (CI) 16.4-33.4]. Sensitivity to detect unresectable disease ranged from 31.6 to 75 % with a pooled sensitivity of 52.2 % (95 % CI 47.1-57.2). Sensitivity was highest for peritoneal metastases (80.7 %, 95 % CI 70.9-88.3). Subgroup analysis revealed that the yield and sensitivity tended to be lower for studies after 2010. Considerable heterogeneity was detected among the studies. CONCLUSIONS: The results of the pooled analyses suggest that one in four patients with potentially resectable PHC benefits from SL. Given considerable heterogeneity, a trend to lower yield in more recent studies and further improvement of preoperative imaging over time, the routine use of SL seems discouraging. Studies that identify predictors of unresectability, that enable selection of patients who will benefit the most from this procedure, are needed.

Percutaneous Preoperative Biliary Drainage for Resectable Perihilar Cholangiocarcinoma: No Association with Survival and No Increase in Seeding Metastases.

BACKGROUND: Endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) are both used to resolve jaundice before surgery for perihilar cholangiocarcinoma (PHC). PTBD has been associated with seeding metastases. The aim of this study was to compare overall survival (OS) and the incidence of initial seeding metastases that potentially influence survival in patients with preoperative PTBD versus EBD. METHODS: Between 1991 and 2012, a total of 278 patients underwent preoperative biliary drainage and resection of PHC at 2 institutions in the Netherlands and the United States. Of these, 33 patients were excluded for postoperative mortality. Among the 245 included patients, 88 patients who underwent preoperative PTBD (with or without previous EBD) were compared to 157 patients who underwent EBD only. Survival analysis was done with Kaplan-Meier and Cox regression with propensity score adjustment. RESULTS: Unadjusted median OS was comparable between the PTBD group (35 months) and EBD-only group (41 months; P = 0.26). After adjustment for propensity score, OS between the PTBD group and EBD-only group was similar (hazard ratio, 1.05; 95 % confidence interval, 0.74-1.49; P = 0.80). Seeding metastases in the laparotomy scar occurred as initial recurrence in 7 patients, including 3 patients (3.4 %) in the PTBD group and 4 patients (2.7 %) in the EBD-only group (P = 0.71). No patient had an initial recurrence in percutaneous catheter tracts. CONCLUSIONS: The present study found no effect of PTBD on survival compared to patients with EBD and no increase in seeding metastases that developed as initial recurrence. These data suggest that PTBD can safely be used in preoperative management of PHC.

Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma.

BACKGROUND: Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. METHODS: Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. RESULTS: Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). CONCLUSIONS: Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.