Surgery for Bismuth-Corlette Type 4 Perihilar Cholangiocarcinoma: Results from a Western Multicenter Collaborative Group.

BACKGROUND: Although Bismuth-Corlette (BC) type 4 perihilar cholangiocarcinoma (pCCA) is no longer considered a contraindication for curative surgery, few data are available from Western series to indicate the outcomes for these patients. This study aimed to compare the short- and long-term outcomes for patients with BC type 4 versus BC types 2 and 3 pCCA undergoing surgical resection using a multi-institutional international database. METHODS: Uni- and multivariable analyses of patients undergoing surgery at 20 Western centers for BC types 2 and 3 pCCA and BC type 4 pCCA. RESULTS: Among 1138 pCCA patients included in the study, 826 (73%) had BC type 2 or 3 disease and 312 (27%) had type 4 disease. The two groups demonstrated significant differences in terms of clinicopathologic characteristics (i.e., portal vein embolization, extended hepatectomy, and positive margin). The incidence of severe complications was 46% for the BC types 2 and 3 patients and 51% for the BC type 4 patients (p = 0.1). Moreover, the 90-day mortality was 13% for the BC types 2 and 3 patients and 12% for the BC type 4 patients (p = 0.57). Lymph-node metastasis (N1; hazard-ratio [HR], 1.62), positive margins (R1; HR, 1.36), perineural invasion (HR, 1.53), and poor grade of differentiation (HR, 1.25) were predictors of survival (all p ≤0.004), but BC type was not associated with prognosis. Among the N0 and R0 patients, the 5-year overall survival was 43% for the patients with BC types 2 and 3 pCCA and 41% for those with BC type 4 pCCA (p = 0.60). CONCLUSIONS: In this analysis of a large Western multi-institutional cohort, resection was shown to be an acceptable curative treatment option for selected patients with BC type 4 pCCA although a more technically challenging surgical approach was required.

Hepatopancreatoduodenectomy for Multifocal Cholangiocarcinoma in the Setting of Biliary Papillomatosis.

BACKGROUND: Hepatopancreatoduodenectomy is performed to achieve curative resection of malignant biliary tumors.1 However, the morbidity and mortality associated with this challenging surgical procedure remain high, and optimal indications remain unclear.2-4 Biliary papillomatosis (BP) is a precursor lesion of cholangiocarcinoma. This video shows hepatopancreatoduodenecomy for multifocal cholangiocarcinoma in the setting of BP. PATIENT: A 75-year-old man with a medical history of cholecystectomy presented with obstructive jaundice. Magnetic resonance colangiopancreatography and computed tomography scan showed diffuse biliary dilation with mild enhancing nodularities in the whole extrahepatic bile duct. Cholangioscopy with biopsies proved cholangiocarcinoma arising from BP at the prepapillary common bile duct (CBD) and the biliary confluence. The second-order right ducts were free of disease. The patient underwent nasobiliary drainage and was considered for hepatopancreatoduodenecomy. TECHNIQUE: A right subcostal incision was performed. Intraoperative ultrasound showed BP of the intrapancreatic CBD spreading only to the left bile duct. En bloc resection of the left liver, caudate lobe, and CBD was performed together with pylorus-preserving pancreatoduodenectomy. The reconstruction phase was performed on a single-loop by duct-to-mucosa pancreatojejunostomy, two-duct biliojejunostomy with mucosa-to-mucosa alignment, and duodenojejunostomy. Transanastomotic external stents were used for biliary and pancreatic drainage. Histopathologic examination confirmed foci of cholangiocarcinoma arising from BP. Resection margins were negative. Lymph node metastasis, microvascular invasion, perineural invasion, and mucin secretion were absent. The patient was discharged on postoperative day 14 without complications. At the 2-year follow-up assessment, he was alive and free of disease. CONCLUSION: Cholangiocarcinoma arising from BP is a proper indication for hepatopancreatoduodenectomy. The long-term oncologic benefits might outweigh the possible perioperative complications.5,6.

Pancreatic resections in patients who refuse blood transfusions. The application of a perioperative protocol for a true bloodless surgery.

BACKGROUND: The refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery. METHODS: The institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used. RESULTS: Perioperative outcomes of 32 Jehovah's Witnesses patients were included. Median age was 67 years (range, 31-77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100-1000) and 470 min (range, 290-595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7-15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1-14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8-54) with no patient requiring transfusion or re-operation and no 90-day mortality. CONCLUSIONS: A multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.

Total Dorsal Pancreatectomy, an Alternative to Total Pancreatectomy: Report of a New Case and Literature Review.

BACKGROUND: Total dorsal pancreatectomy (TDP) is a conservative pancreatic resection that should be considered in cases of benign or low malignant tumors confined to the dorsal pancreas to preserve the viability of both digestive and biliary tracts, and to avoid the endocrine and metabolic consequences of total pancreatectomy. We report a new case of TDP and provide a literature review of this procedure. METHODS: The case reported was a 35-year-old female patient with a solid pseudopapillary tumor. We resected the dorsal segment of the pancreas while preserving the common bile duct, gastroduodenal artery, and pancreaticoduodenal arcades, and the spleen and splenic vessels. The MEDLINE® and Embase® databases were searched for English language studies, case series, or case reports published through August 31, 2017. RESULTS: The postoperative course was uneventful and patient was discharged on postoperative day 11. The patient was alive and in good condition at the 10-year follow-up. To date in English literature, there are only 3 reported cases of TDP, and all cases were patients with intraductal papillary mucinous neoplasia and pancreas divisum. There was no postoperative mortality, and 2 grade B pancreatic fistulas healed 1 month postoperatively. CONCLUSIONS: TDP is a feasible and safe operation for benign or low grade malignant pancreatic tumors involving the dorsal pancreas, as an alternative to total pancreatectomy.

Patterns of gene mutations in bile duct cancers: is it time to overcome the anatomical classification?

BACKGROUND: Two recent studies based on multi-omics data analysis identified distinct subtypes of bile-duct cancers (BDC) with important implications in terms of disease classification and patients' treatment. METHODS: Patients with mutations in KRAS, NRAS, TP53, and ARID1A genes were classified in KRAS/TP53 group while patients with mutations in IDH1-2, BAP1, and PBRM1 were classified in IDH1-2/BAP1/PBRM1 group. The aim of this study was to define long-term outcomes among patients stratified by patterns of genes mutated. RESULTS: Among 105 patients who underwent surgical resection for BDCs, 71 (68%) patients were classified in two groups based on patterns of genes mutated. While in IDH1-2/BAP1/PBRM1 group there were 58%, 22%, and 10% of patients with intrahepatic-cholangiocarcinoma (ICC), perihilar-cholangiocarcinoma (PHCC), and gallbladder cancer (GBC), in KRAS/TP53 group there were 42%, 78%, and 90% of patients with ICC, PHCC, and GBC (p = 0.003), respectively. Patients in IDH1-2/BAP1/PBRM1 group had a 5-year OS of 40% compared with 13% for KRAS/TP53 group (p = 0.032). In a multivariable model adjusted for margins, lymph-node status, microvascular invasion, and tumor grade, patients in KRAS/TP53 group had a 2.1-fold increased risk of death compared with patients in IDH1-2/BAP1/PBRM1 group (p = 0.028). CONCLUSIONS: Genetic data were able to overcome the clinical based staging system in predicting patients' prognosis.

Complications after liver surgery: a benchmark analysis.

BACKGROUND: The best achievable short-term outcomes after liver surgery have not been identified. Several factors may influence the post-operative course of patients undergoing hepatectomy increasing the risk of post-operative complications. We sought to identify risk-adjusted benchmark values [BMV] for liver surgery. METHODS: The National Surgery Quality Improvement Program (NSQIP) database was used to develop Bayesian models to estimate risk-adjusted BMVs for overall and liver related (post-hepatectomy liver failure [PHLF], biliary leakage [BL]) complications. A separate international multi-institutional database was used to validate the risk-adjusted BMVs. RESULTS: Among the 11,243 patients included in the NSQIP database, the incidence of complications, PHLF, and BL was 36%, 5%, and 8%, respectively. The risk-adjusted BMVs for complication (range, 16-72%), PHLF (range, 1%-20%), and BL (range, 4%-22%) demonstrated a high variability based on patients characteristics. When tested using an international database including nine institutes, the risk-adjusted BMVs for complications ranged from 26% (Institute-4) to 43% (Institute-1), BMVs for PHLF between 3% (Institute-3) and 12% (Institute-5), while BMVs for BL ranged between 5% (Institute-4) and 9% (Institute-7). CONCLUSIONS: Multiple factors influence the risk of complications following hepatectomy. Risk-adjusted BMVs are likely much more applicable and appropriate in assessing "acceptable" benchmark outcomes following liver surgery.

The Tumor Burden Score: A New "Metro-ticket" Prognostic Tool For Colorectal Liver Metastases Based on Tumor Size and Number of Tumors.

OBJECTIVE: To apply the principles of the Metro-ticket paradigm to develop a prognostic model for patients undergoing hepatic resection of colorectal liver metastasis (CRLM). BACKGROUND: Whereas the hepatocellular "Metro-ticket" prognostic tool utilizes a continuum of tumor size and number, a similar concept of a CRLM Metro-ticket paradigm has not been investigated. METHODS: Tumor Burden Score (TBS) was defined using distance from the origin on a Cartesian plane incorporating maximum tumor size (x-axis) and number of lesions (y-axis). The discriminatory power [area under the curve (AUC)] and goodness-of-fit (Akaike information criteria) of the TBS model versus standard tumor morphology categorization were assessed. The TBS model was validated using 2 external cohorts from Asia and Europe. RESULTS: TBS (AUC 0.669) out-performed both maximum tumor size (AUC 0.619) and number of tumors (AUC 0.595) in predicting overall survival (OS) (P < 0.05). As TBS increased, survival incrementally worsened (5-year OS: zone 1, zone 2, and zone 3-68.9%, 49.4%, and 25.5%; P < 0.05). The stratification of survival based on traditional tumor size and number cut-off criteria was poor. Specifically, 5-year survival for patients in category 1, category 2, and category 3 was 58.3%, 45.5%, and 50.6%, respectively (P > 0.05). The corrected Akaike score information criteria value of the TBS model (2865) was lower than the traditional tumor morphologic categorization model (2905). Survival analysis revealed excellent prognostic discrimination for the TBS model among patients in both external cohorts (P< 0.05). CONCLUSIONS: An externally validated "Metro-ticket" TBS model had excellent prognostic discriminatory power. TBS may be an accurate tool to account for the impact of tumor morphology on long-term survival among patients undergoing resection of CRLM.

Patterns of Distribution of Hepatic Nodules (Single, Satellites or Multifocal) in Intrahepatic Cholangiocarcinoma: Prognostic Impact After Surgery.

OBJECTIVE: We aimed to compare the clinicopathological features and survival after surgery of patients with intrahepatic cholangiocarcinoma (ICC) according to the patterns of distribution of hepatic nodules. METHODS: A retrospective analysis of a multi-institutional series of 259 patients with resected ICC was carried out. Patients were further classified according to the pattern of distribution of hepatic nodules: single tumors (type I), single tumors with satellites in the same liver segment (type II), or multifocal tumors (type III). RESULTS: Overall, 64.5% of patients had type I, 21.9% had type II, and 13.5% had type III. The 5-year overall survival rate was 49.4, 34.2, and 9.9% for types I, II, and III, respectively (p < 0.001). A multivariate survival analysis identified the following independent prognostic factors: pattern types II and III (p = 0.001 and p = 0.001, respectively), size ≥ 50 mm (p = 0.021), lymph node (LN) metastases (p = 0.005), and R1 resections (p = 0.019). We stratified survival for each type of pattern according to the other prognostic factors identified in the multivariate analysis. N0 and R0 patients with type II and III tumors had encouraging long-term results. Conversely, patients with LN metastases and R1 resections had poor prognosis, particularly patients with type III tumors. CONCLUSION: ICC has distinct patterns of distribution with different prognoses that should be considered when making therapeutic decisions. Patients with type III tumors had a significantly worse prognosis, and the benefits of upfront surgery should be carefully evaluated.

Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients.

BACKGROUND: Cholangiocarcinoma can be classified in intrahepatic cholangiocarcinoma (ICC) and perihilar cholangiocarcinoma (PCC). Moreover, PCC includes two different forms: extrahepatic (EH) PCC, which arises from the perihilar EH large ducts, and intrahepatic (IH) PCC, in which a significant liver mass invades the perihilar bile ducts. In this study, we investigated the molecular profile and molecular prognostic factors in EH-PCC, IH-PCC, and ICC submitted to curative surgery. METHODS: Ninety-one patients with cholangiocarcinoma (38 EH-PCC, 18 IH-PCC, and 35 ICC), who underwent curative surgery in a single tertiary hepatobiliary surgery referral center were assessed for mutational status in 56 cancer-related genes. RESULTS: The most frequently mutated genes in EH-PCC were KRAS (47.4 %), TP53 (23.7 %) and ARID1A (15.8 %); in IH-PCC were KRAS (22.2 %), PBRM1 (16.7 %), and PIK3CA (16.7 %); and in ICC were IDH1 (17.1 %), NRAS (17.1 %), and BAP1 (14.3 %). The presence of mutations in ALK, IDH1, and TP53 genes was significantly associated with poor prognosis in patients with EH-PCC (p < 0.001, p = 0.043, and p = 0.019, respectively). Mutation of the TP53 gene was significantly associated with poor prognosis in patients with IH-PCC (p = 0.049). The presence of mutations in ARID1A, PIK3C2G, STK11, TGFBR2, and TP53 genes was significantly associated with poor prognosis in patients with ICC (p = 0.012, p = 0.030, p = 0.030, p = 0.011, and p = 0.011, respectively). CONCLUSIONS: Mutational gene profiling identified different gene mutations in EH-PCC, IH-PCC, and ICC. Moreover, our study reported specific prognostic genes that can identify patients with poor prognosis after curative surgery who may benefit from traditional or target adjuvant treatments.

Management of pancreatic trauma: A pancreatic surgeon's point of view.

BACKGROUND: Pancreatic trauma occurs in 0.2% of patients with blunt trauma and 1-12% of patients with penetrating trauma. Traumatic pancreatic injuries are characterised by high morbidity and mortality, which further increase with delayed diagnoses. The diagnosis of pancreatic trauma is challenging. Signs and symptoms can be non-specific or even absent. METHODS: A critical review of studies reporting the management and outcomes of pancreatic trauma was performed. RESULTS: The management of pancreatic trauma depends on the haemodynamic stability of the patient, the degree and location of parenchymal injury, the integrity of the main pancreatic duct, and the associated injuries to other organs. Nevertheless, the involvement of the main pancreatic duct is the most important predictive factor of the outcome. The majority of pancreatic traumas are managed by medical treatment (parenteral nutrition, antibiotic therapy and somatostatin analogues), haemostasis, debridement of devitalised tissue and closed external drainage. If a proximal duct injury is diagnosed, endoscopic transpapillary stent insertion can be a viable option, while surgical resection by pancreaticoduodenectomy is restricted to an extremely small number of selected cases. Injuries of the distal parenchyma or distal duct may be managed with distal pancreatectomy with spleen preservation. At the pancreatic neck, when pancreatic transection occurs without damage to the parenchyma, a parenchyma-sparing procedure is feasible. CONCLUSION: The management of pancreatic injuries is complex and often requires a multidisciplinary approach. Here, we propose a management algorithm that is based on parenchymal damage and the site of duct injury.

Head dorsal pancreatectomy: an alternative to the pancreaticoduodenectomy for not enucleable benign or low-grade malignant lesions.

BACKGROUND: Head dorsal pancreatectomy (HDP) is a segmental pancreatic resection, conservative variant of total dorsal pancreatectomy, applied to preserve the functional pancreatic parenchyma as an alternative to pancreaticoduodenectomy in not enucleable benign or low-grade malignant lesions. The absences of biliary and gastrointestinal resection/reconstruction are the other advantages of the technique. METHODS: We reported a case of HDP performed in a female 39-year-old patient for a neuroendocrine tumour of the dorsal portion of the pancreatic head. RESULTS: The superior mesenteric vein was dissected from the pancreatic neck. The pancreas was transected at the left margin of the superior mesenteric vein. After identification and mobilisation of gastroduodenal artery and the anterior superior pancreatico-duodenal artery, the head dorsal segment was dissected stepwise from the duodenal wall toward the common bile duct plane; the dissection of the pancreatic parenchyma was completed along the anterior surface of the common bile duct. An end-to-side duct-to-mucosa pancreaticojejunostomy was performed. The main pancreatic duct in the ventral segment on the dissection parenchymal surface was ligated. With the inclusion of this case, there are a total of 3 cases involving resection of the dorsal portion of the pancreatic head reported in the literature. CONCLUSION: HDP seems to be technically feasible and safe for not enucleable benign or low-grade malignant neoplasms involving the dorsal pancreatic head. However, due to the singularity of the indications and the few cases reported in the literature, further studies are needed to validate the technique.

Role of preoperative biliary drainage in jaundiced patients who are candidates for pancreatoduodenectomy or hepatic resection: highlights and drawbacks.

INTRODUCTION: In this review of the literature, we analyze the indications for preoperative drainage in jaundiced patients who are candidates for pancreaticoduodenectomy (PD) or major hepatectomy due to periampullary or proximal bile duct neoplasms. OBJECTIVE: The aim of this study is to review the literature and to report on the current management of jaundiced patients with periampullary or proximal bile duct neoplasms who are candidates for PD or major liver resection. BACKGROUND: Jaundiced patients represent a major challenge for surgeons. Alterations and functional impairment caused by jaundice increase the risk of surgery; therefore, preoperative biliary decompression has been suggested. METHODS: A literature review was performed in the MEDLINE database to identify studies on the management of jaundice in patients undergoing PD or liver resection. Papers considering palliative drainage in jaundiced patients were excluded. RESULTS: The first group of papers considered patients affected by middle-distal obstruction from periampullary neoplasms, in which preoperative drainage was applied selectively. The second group of papers evaluated patients with biliary obstructions from proximal biliary neoplasms. In these cases, Asian authors and a few European authors considered it mandatory to drain the future liver remnant (FLR) in all patients, while American and most European authors indicated preoperative drainage only in selected cases (in malnourished patients and in those with hypoalbuminemia, cholangitis or long-term jaundice; with an FLR < 30% or 40%) given the high risk of complications of drainage (choleperitoneum, cholangitis, bleeding, and seeding). The optimal type of biliary drainage is still a matter of debate; recent studies have indicated that endoscopy is preferable to percutaneous drainage. Although the type of endoscopic biliary drainage has not been clearly established, the choice is made between plastic stents and short, covered, metallic stents, while other authors suggest the use of nasobiliary drainage. CONCLUSIONS: : A multidisciplinary evaluation (made by a surgeon, biliary endoscopist, gastroenterologist, and radiologist) of jaundiced neoplastic patients should be performed before deciding to perform biliary drainage. Middle-distal obstruction in patients who are candidates for PD does not usually require routine biliary drainage. Proximal obstruction in patients who are candidates for major hepatic resection in the majority of cases requires a drain; however, the type, site, number, and approach must be defined and tailored according to the planned hepatic resection. Recently, the use of preoperative biliary drainage limited to the FLR has been a suggested strategy. However, multicenter, randomized, controlled trials should be conducted to clarify this issue.

How much remnant is enough in liver resection?

BACKGROUND: Liver resection represents the first choice of treatment for primary and secondary liver malignancies, offering the patient the best chance of long-term survival. The extensive use of major hepatectomy increases the risk of post-hepatectomy liver failure (PHLF), which is associated with a high frequency of postoperative complications, mortality and increased length of hospital stay. AIMS: The aim of this review is to investigate the different risk factors related to the occurrence of PHLF and to identify the limits for a safe liver resection in patients with normal liver and injured liver (cirrhosis, cholestasis, steatosis and post-chemotherapy liver injury). METHODS: A literature search was undertaken in PubMed and related search engines, looking for articles relating to hepatic failure following hepatectomy in normal liver or injured liver. RESULTS: In spite of improvements in surgical and postoperative management, the parameters determining how much liver can be resected are still largely undefined. A number of preoperative, intraoperative and postoperative factors all contribute to the likelihood of liver failure after surgery. The safe limits for liver resection can be estimated from the data of the literature for patients with normal liver and for those with different types of liver injury. CONCLUSIONS: Preoperative assessment that includes evaluation of liver volume and function of the remnant liver is a mandatory prerequisite before major hepatectomy. The critical residual liver volume for patients able to predict PHLF is mainly related to the presence of pre-existing liver disease and liver function. Among patients with normal liver, the limit for safe resection ranges from 20 to 30% future remnant liver of total liver volume. In patients with injured liver (cirrhosis, cholestasis or steatosis), preoperative assessment of the risk of PHLF should include future remnant liver volumetry and accurate liver function evaluation, including different dynamic liver function tests.

Prognostic significance of lymph node ratio after resection of peri-hilar cholangiocarcinoma.

BACKGROUND: Lymph node (LN) metastases are a major negative prognostic factor for peri-hilar cholangiocarcinoma (PCC). Prognostic significance of the extent of LN dissection, number of metastatic LN and the lymph node ratio (LNR) are still under debate. AIMS: The aims of the present study were to evaluate the prognostic value of the LN status, the total number of LNs evaluated and LNR in PCC. METHODS: Between 1990 and 2008, 62 patients with PCC submitted to surgical resection with curative intent were retrospectively evaluated. Number and status of harvested LN were recorded. RESULTS: In 53 patients (85.4%) regional lymphadenectomy was performed. Median number of LNs examined was 7 (range 1-25). Median survival was 41.9 months in patients with N0 compared with 22.7 months in 21 patients (39.6%) with N+ (P= 0.03). Median survival was 3, 18.5 and 29 months for patients with 0, 1-3 and >3 LN retrieved, respectively (P < 0.01). Five-year survival for patients above and below the LNR cut-off value of 0.25 was 0% and 22.5%, respectively (P= 0.03). CONCLUSIONS: LN metastases are a major prognostic factor for survival after surgical resection of PCC. The number of LN harvested and LNR showed high prognostic value.

Does intrahepatic cholangiocarcinoma have better prognosis compared to perihilar cholangiocarcinoma?

BACKGROUND AND OBJECTIVES: Cholangiocarcinoma can be classified as intrahepatic (ICC) or perihilar (PCC). The objectives of this study is to evaluate the surgical outcomes of patients with PCC and ICC, identify the main prognostic factors related to survival and compare the outcome and the prognostic factors of PCC and ICC. METHODS: Ninety-five out of 152 patients observed between January 1990 and December 2007 at Surgical Division of University of Verona Medical School underwent the resection of ICC (33 patients) or PCC (62 patients). RESULTS: Overall median survival was 24 months with a 3- and 5-year survival rate of 45% and 23%, respectively. Prognostic factors for survival were macroscopic types of the tumor, the resection of extrahepatic bile duct, radical resection, lymph node metastases, and macro-vascular invasion. Survival was related with the macroscopic type of the tumors with a 5-year survival rate of 26% and 13% for ICC and PCC, respectively. Univariate analysis identified that negative clinico-pathological factors where significant more frequently found in PCC compared to ICC. CONCLUSION: We identified that ICC have longer survival rate compared to PCC. PCC showed a higher frequency of negative clinico-pathological factors such as non-radical (R+) resection, perineural infiltration and macro-vascular invasion.

Multigene mutational profiling of biliary tract cancer is related to the pattern of recurrence in surgically resected patients.

The aim of the present study was to investigate the relationship between the mutational gene profile and recurrence in biliary tract cancers (BTC). A total of 103 specimens of patients with BTC, who underwent curative surgery in a single tertiary HPB surgery referral center from 1990 to 2012, were assessed for mutational status in 52 cancer-related genes. Considering the different types of BTC, the 5-year recurrence-free survival (RFS) rate was 16.7% (median RFS 7 months) in gallbladder cancer, 42.9% (median RFS 26.4 months) in intrahepatic cholangiocarcinoma, and 19.7% (median RFS 16.5 months) in perihilar cholangiocarcinoma, p = 0.166. At the multivariate analysis including clinical, pathological, and molecular features, the factors independently related to RFS were radicality of surgery (OR 2.050, CI 1.104-3.807, p = 0.023), LN status (OR 1.835, CI 1.006-3.348, p = 0.048), mutational status of ARID1A (OR 2.566, CI 1.174-5.608, p = 0.018), and TP53 (OR 2.805, CI 4.432-5.496, p = 0.003). ARID1A mutation was associated with a local and systemic recurrence in the 43% and 29% of cases, respectively; and TP53 mutation was associated with a local and systemic recurrence in the 29% and 41% of cases. Moreover, TP53 was most commonly mutated in tumor of patients with early recurrence, p = 0.044. ARID1A and TP53 mutations seem to be related to poor outcome after surgery and may be considered molecular predictors of the biological aggressiveness in BTC.

Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: We aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). METHODS: A retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR). Univariate and multivariate analysis were applied to define the impact of VR on postoperative outcomes and survival. RESULTS: Thirty-one patients (11.5%) underwent VR: 15 (5.6%) to PVR and 16 (5.9%) to CVR. R0 resection rates were 73.6% in NVR, 73.3% of PVR and 68.8% in CVR. The postoperative mortality rate was increased in VR groups: 2.5% in NVR, 6.7% in PVR and 12.5% in CVR. The 5-years overall survival (OS) rates progressively decreased from 38.4% in NVR, to 30.1% in CVR and to 22.2% in PVR, p = 0.030. However, multivariable analysis did not confirm an association between VR and prognosis. The following prognostic factors were identified: size ≥50 mm, patterns of distribution of hepatic nodules (single, satellites or multifocal), lymph-node metastases (N1) and R1 resections. In the VR group the 5-years OS rate in patients without lymph-node metastases undergoing R0 resection (VRR0N0) was 44.4%, while in N1 patients undergoing R1 resection was 20% (p < 0.001). CONCLUSION: Vascular resection (PVR and CVR) is associated with higher operative risk, but seems to be justified by the good survival results, especially in patients without other negative prognostic factors (R0N0 resections).