[A Case of Pancreatic Adenocarcinoma with Inferior Vena Cava Invasion].

A 66-year-old Japanese woman was admitted to our hospital for jaundice. Abdominal computed tomography(CT) showed dilatation of the intra- and extra-hepatic bile duct, and a hypovascular lesion measuring 30mm in diameter in the head of the pancreas. This tumor was in contact with the(superior mesenteric vein: SMV)and(inferior vena cava: IVC), but there were no obvious signs of invasion. Upper gastrointestinal endoscopy showed obstruction of the duodenum. We chose to perform an upfront surgery, considering the patient's general condition being stable and the difficulties associated with endoscopic biliary drainage. During surgery, stiff attachment between the tumor and IVC was identified and wedge resection of the IVC wall was performed. SMV resection and end-to-end reconstruction were also carried out. Pathological studies of the surgical specimen revealed direct invasion by the pancreatic adenocarcinoma into the adventitia of the IVC. The postoperative course was uneventful, and the patient was discharged from the hospital on the 27th postoperative day; she underwent adjuvant chemotherapy(S-1 100mg/day)and is still alive without tumor recurrence, 21 months after surgery. Cases of resected pancreatic adenocarcinoma directly invading the IVC are rare. In this case, pancreaticoduodenectomy along with wedge resection of the IVC wall could safely be performed, and no complications were observed. There is a need for further accumulation of similar cases.

[Hepatic and Pancreatic Metastases of a Rectal Gastrointestinal Stromal Tumor in a Patient with Long-Term Survival following Combined Therapy-ACase Report].

A 68-year-old woman underwent Miles' surgery with a diagnosis of a rectalgastrointestinalstromaltumor (GIST)in 2004. In 2005 and 2006, she developed liver metastases that were surgically removed, but once again in June 2006, she presented with liver metastasis, and imatinib therapy(400mg/day)was administered. In October 2016, she was diagnosed with progression of liver metastasis, and a tumor in the pancreatic body was identified on a CT scan. The patient was referred to our institution for treatment. We performed right hepatectomy and distalpancreatectomy in January 2017. Immunohistochemically, the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. The pathological diagno- sis was a high-risk GIST showing 43mitoses per 50 high-power fields. Imatinib therapy(400mg/day)was administered after surgery. She is currently alive without recurrence.

Pancreatic inflammation and atrophy are not associated with pancreatic cancer concomitant with intraductal papillary mucinous neoplasm.

BACKGROUND: Inflammation-induced carcinogenesis in pancreatic ductal adenocarcinoma (PDAC) has been reported; however, its involvement in PDAC with intraductal papillary mucinous neoplasm (IPMN) remains unclear. We herein investigated the relationship between pancreatic atrophy and inflammation and the incidence of PDAC concomitant with IPMN. METHODS: This study included 178 consecutive patients who underwent surgical resection for PDAC with IPMN (N = 21) and IPMN (N = 157) between April 2001 and October 2016. A multivariable logistic regression analysis was conducted to assess the relationship between pancreatic inflammation and atrophy and the incidence of PDAC concomitant with IPMN, with adjustments for clinical characteristics and imaging features. Pathological pancreatic inflammation and atrophy were evaluated in resected specimens. RESULTS: High degrees of pancreatic inflammation and atrophy were not associated with the incidence of PDAC with IPMN (multivariable odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.07 to 3.33, P = .52, adjusted by clinical characteristics, OR = 0.9, 95% CI = 0.10 to 5.86, P = .91, adjusted by imaging studies; OR = 0.2, 95% CI = 0.009 to 1.31, P = .10, adjusted by clinical characteristics, OR = 0.2, 95% CI = 0.01 to 1.43, P = .12, adjusted by imaging studies, respectively). CONCLUSIONS: Pancreatic inflammation and atrophy were not associated with pancreatic cancer concomitant with IPMN.

Impact of resection and ablation for single hypovascular hepatocellular carcinoma ≤2 cm analysed with propensity score weighting.

BACKGROUND AND AIMS: Small hypovascular hepatocellular carcinoma (HCC) ≤2 cm is biologically less aggressive than hypervascular one, however, the optimal treatment is still undetermined. The efficacy of surgical resection (SR), radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) was evaluated. METHODS: The 853 (SR, 176; RFA, 491; PEI, 186) patients were enrolled who met Child-Pugh A/B, single hypovascular HCC ≤2 cm pathologically proven, available tumour differentiation and absence of macrovascular invasion and extrahepatic metastasis. Overall and recurrence-free survivals were compared in original and a propensity score weighted pseudo-population with 732 patients. RESULTS: The median follow-up time and tumour size were 2.8 years and 1.47 cm respectively. In original population, multivariate Cox regression showed no significant difference for overall survival among three groups. In pseudo-population, Cox regression also revealed no significant difference for overall survival among them, although SR (HR, 0.56; 95% CI, 0.36-0.86) and RFA (HR, 0.75; 95% CI, 0.57-1.00) groups had significantly lower recurrence than PEI group. The overall survival rates at 3 and 5 years for the SR, RFA and PEI groups were 94%/70%, 90%/75% and 94%/73% respectively. Corresponding recurrence-free survival rates were 64%/54%, 59%/41% 48%/33% respectively. Subgroup analysis revealed no significant survival benefit of SR compared with non-SR. No treatment-related death occurred. CONCLUSIONS: For patients with single hypovascular HCC ≤2 cm, no significant difference for overall survival was first identified among 3 treatment groups. The SR or RFA could be recommended, and PEI would be alternative to RFA.

Hemostatic Efficacy and Safety of the Novel Medical Adhesive, MAR VIVO-107, in a Rabbit Liver Resection Model.

BACKGROUND: Topical hemostatic agents are useful when hepatic hemorrhage is difficult to control. The aim of this study was to evaluate the hemostatic efficacy and safety of a biodegradable polyurethane-based adhesive, MAR VIVO-107 (MAR), in comparison with a clinically used fibrin glue. METHODS: Thirty female New Zealand white rabbits were randomly assigned to 3 study groups as follows: MAR (n = 10), fibrin glue (n = 10), and saline groups (n = 10). After standardized partial liver resection was performed, each agent was immediately applied to the wound area. Bleeding time until hemostasis and blood loss were recorded. After 7 days, body weight, hematology parameters, and serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured. Simultaneously, the severity of intra-abdominal adhesion was evaluated. RESULTS: The mean bleeding time in the MAR (38 ± 10 s) and fibrin glue groups (65 ± 17 s) was significantly shorter than that in the saline group (186 ± 12 s). Similarly, the mean blood loss in the MAR (9 ± 3 g) and fibrin glue groups (9 ± 3 g) was significantly less than that in the saline group (23 ± 4 g). No significant differences in bleeding time and blood loss were found between the MAR and fibrin glue groups. The postoperative survival rate was 100% in all the groups. Body weight as well as hematological and serum biochemical values on day 7 were within the small and physiological range when compared with the preoperative baseline values, and significant differences were not detected among the MAR, fibrin glue, and saline groups. The severities of adhesion were similar between the 3 groups. CONCLUSION: Our data demonstrated that MAR was not inferior to fibrin glue in terms of hemostatic efficacy and safety.

Dichotomy in intrahepatic cholangiocarcinomas based on histologic similarities to hilar cholangiocarcinomas.

Intrahepatic cholangiocarcinomas were classified into two types based on their microscopic appearance. Tumors with histologic similarities to hilar cholangiocarcinomas (predominantly ductal adenocarcinomas with minor tubular components, if present, restricted to the invasive front) were defined as the perihilar type, whereas the others were classified as peripheral cholangiocarcinomas. Among the 47 cases examined in the present study, 26 (55%) were classified as the perihilar type, whereas 21 (45%) were the peripheral type. The perihilar type had higher pT stages and more frequently showed a periductal-infiltrating gross appearance and microscopic perineural infiltration than peripheral cholangiocarcinomas. The presence of low-grade biliary intraepithelial neoplasia in the adjacent bile ducts was only found in perihilar cholangiocarcinomas (6/21, 29%). The immunophenotype also differed between the two types with MUC5AC and MUC6 being more commonly expressed in the perihilar type. One-third of perihilar cholangiocarcinomas lacked the expression of SMAD4, suggesting SMAD4 mutations, whereas the loss of BAP1 expression and IDH1 mutations were almost restricted to the peripheral type (35 and 15%, respectively). Patients with perihilar cholangiocarcinoma had worse overall survival than those with peripheral cancer (P=0.027). A multivariate analysis identified the histologic classification as an independent prognostic factor (P=0.005, HR=3.638). Comparisons between intrahepatic and hilar cholangiocarcinomas also revealed that the molecular features and prognosis of perihilar cholangiocarcinomas were very similar to those of hilar cholangiocarcinomas. In conclusion, this histology-based classification scheme of intrahepatic cholangiocarcinomas will be useful and clinically relevant because it represents different underlying molecular features and has an independent prognostic value.

Pancreatic Duct Involvement in Well-Differentiated Neuroendocrine Tumors is an Independent Poor Prognostic Factor.

BACKGROUND: The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs. METHODS: The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection. RESULTS: MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P < 0.001), with a 5 years recurrence-free rate of 41%. On multivariate analysis, MPD involvement was significantly associated with nodal metastasis [odds ratio (OR) 16; 95% confidence interval (CI) 3.8-89; P < 0.001] and recurrence (OR 8.0; 95% CI 1.7-46; P = 0.009). The radiology-pathology correlation revealed that stenosis of the MPD was due to periductal and/or intraductal tumor invasion. Cases with MPD involvement had microscopic venous invasion (P = 0.010) and perineural infiltration (P = 0.002) more frequently than did those with no ductal infiltration. CONCLUSIONS: MPD involvement in PNETs may serve as an imaging sign indicating an aggressive clinical course.

Chronic Pancreatitis Finding by Endoscopic Ultrasonography in the Pancreatic Parenchyma of Intraductal Papillary Mucinous Neoplasms Is Associated with Invasive Intraductal Papillary Mucinous Carcinoma.

BACKGROUND/OBJECTIVES: The recent guideline for intraductal papillary mucinous neoplasms (IPMNs) focuses on morphological features of the lesion as signs of malignant transformation, but ignores the background pancreatic parenchyma, including features of chronic pancreatitis (CP), which is a risk factor for pancreatic malignancies. Endoscopic ultrasonography frequently reveals evidence of CP (EUS-CP findings) in the background pancreatic parenchyma of patients with IPMNs. Therefore, we investigated whether background EUS-CP findings were associated with malignant IPMN. METHODS: The clinical data of 69 consecutive patients with IPMNs who underwent preoperative EUS and surgical resection between April 2010 and October 2014 were collected prospectively. The association of EUS-CP findings (total number of EUS-CP findings; 0 vs. ≥1) with invasive IPMN was examined. The association of EUS-CP findings with pathological changes of the background pancreatic parenchyma (atrophy/inflammation/fibrosis) was also examined. RESULTS: Among patients with EUS-CP findings, invasive intraductal papillary mucinous carcinoma (IPMC) was significantly more frequent than among patients without EUS-CP findings (42.5% [17/40] vs. 3.4% [1/29], p = 0.0002). In addition, patients with EUS-CP findings had higher grades of pancreatic atrophy and inflammation than patients without EUS-CP findings (atrophy: 72.5% [29/40] vs. 34.5% [10/29], p = 0.003; inflammation: 45.0% [18/40] vs. 20.7% [6/29], p = 0.04). CONCLUSIONS: In IPMN patients, detection of EUS-CP findings in the background pancreatic parenchyma was associated with a higher prevalence of invasive IPMC. Accordingly, EUS examination should not only assess the morphological features of the lesion itself, but also EUS-CP findings in the background parenchyma.

Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence.

BACKGROUND: The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). METHODS: Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. RESULTS: Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). CONCLUSIONS: Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence.

Association between serum SPan-1 and lymph node metastasis in invasive intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND AND AIM: Lymph node metastasis predicts poorer prognoses in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Factors associated with lymph node metastasis of invasive IPMN remain unclear. Therefore, this study aimed to define factors associated with lymph node metastasis of invasive IPMN. METHODS: Between June 2000 to August 2015, 156 consecutive patients with IPMN underwent surgical resection at Kobe University Hospital, and were enrolled in this study. The relationship between lymph node metastasis and clinical characteristics, including imaging studies and serum tumor markers, was evaluated. A multivariate logistic regression analysis was performed to assess the relationship between serum tumor markers and the presence of lymph node metastasis of IPMN, adjusted for clinical characteristics. RESULTS: Lymph node metastasis was observed in 7.7% (12/156) of IPMNs via a pathological examination. The multivariate logistic regression analysis revealed that serum SPan-1 was associated with the presence of lymph node metastasis of IPMN (odds ratio [OR] = 7.32; 95% confidence interval [CI] = 1.10 to 56.0; P = 0.04). In addition, survival was poorer among serum SPan-1-positive patients than SPan-1 negative patients (Log-rank test; P = 0.0002). Lymph node enlargement was detected preoperatively on computed tomography scans in only 16.7% (2/12) of cases that were positive for lymph node metastasis. CONCLUSIONS: Elevated serum SPan-1 was associated with lymph node metastasis in this cohort of patients who underwent resection for invasive IPMN.

Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience.

The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.

Hemorrhagic and Thromboembolic Complications after Hepato-Biliary-Pancreatic Surgery in Patients Receiving Antithrombotic Therapy.

BACKGROUND: Perioperative management for patients receiving long-term anticoagulant (AC) and antiplatelet (AP) therapy is a great concern for surgeons. This single-center retrospective study evaluated the risks of hemorrhage and thromboembolism after hepato-biliary-pancreatic (HBP) surgery in such patients. METHODS: Between 2009 and 2014, 886 patients underwent HBP surgery. Patients were categorized into the AC (n = 39), AP (n = 77), or control (n = 770) group according to the administration of antithrombotic drugs. Perioperative management of AC and AP therapies followed the guidelines of the Japanese Circulation Society. The incidences of hemorrhage and thromboembolism were compared among groups. We used 1:1 propensity score matching and compared the incidences between the matched pairs. RESULTS: There were 0, 1 (1.3%), and 26 (3.4%) hemorrhagic complications in the AC, AP, and control groups, respectively (p = 0.16). There were 0, 1 (1.3%), and 6 (0.8%) thromboembolic complications in the AC, AP, and control groups, respectively (p = 0.66). There was no significant difference in hemorrhagic and thromboembolic complications between the propensity-matched pairs. CONCLUSION: The incidences of hemorrhage and thromboembolism after HBP surgery in patients receiving long-term AC and AP therapies are within acceptable ranges.

New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch.

PURPOSE: Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT. METHODS: Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types. RESULTS: The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively. CONCLUSIONS: BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.

Preoperative neutrophil-to-lymphocyte ratio as a predictor of survival after reductive surgery plus percutaneous isolated hepatic perfusion for hepatocellular carcinoma: a retrospective analysis.

PURPOSE: We assessed the predictive value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients who underwent a two-stage treatment combining reductive surgery and percutaneous isolated hepatic perfusion for multiple hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: Forty-two patients underwent the two-stage treatment between January 2000 and December 2014 at Kobe University Hospital (Hyogo, Japan). The NLR was calculated from lymphocyte and neutrophil counts in the preoperative routine blood test. Clinical data and overall survival were compared statistically and multivariate analysis was done to identify prognostic factors. RESULTS: The median survival of patients with a preoperative NLR > 2.3 was 14.9 months (n = 13), whereas that of patients with a preoperative NLR ≤ 2.3 was 26.1 months (n = 29; P = 0.022). A preoperative NLR > 2.3 was an independent prognostic factor in patients with multiple HCC with PVTT [hazard ratio (HR) 2.329; 95 % confidence interval (CI) 1.058-5.667; P = 0.036]. CONCLUSION: Based on the results of this study, an elevated preoperative NLR is an independent predictive risk factor for patients undergoing two-stage treatment for multiple HCC with PVTT.

Efficacy of the Novel Medical Adhesive, MAR-VIVO-107, in an Acute Porcine Liver Resection Model.

BACKGROUND: Despite modern surgical techniques, insufficient hemostasis after liver trauma is still a major cause of morbidity and mortality after injury. Therefore, efficient hemostatic agents are indicated. In this study, we evaluated the hemostatic efficacy of a novel synthetic wound adhesive (MAR-VIVO-107) based on polyurethane/polyurea, compared with a widely used fibrin adhesive (Tisseel). MATERIALS AND METHODS: Twelve German Landrace pigs were randomly assigned to 2 groups. The animals were operated under sterile conditions. A midline laparotomy was performed and the left liver lobe was isolated and resected, using a surgical scissor, in order to induce hepatic trauma. MAR-VIVO-107 or Tisseel was applied to the resected area. The animals were monitored for 60 minutes; thereafter, they were sacrificed under anesthesia. Blood and tissue samples were collected pre- and postresection for biochemical and hematological analyses. RESULTS: MAR-VIVO-107 versus Tisseel (mean ± SD, P value)-postsurgical survival rate was 100% in both groups. Bleeding time was significantly higher in Tisseel compared with MAR-VIVO-107 (10.3 ± 5.0 vs 3.7 ± 1.5 minutes, P = .0124). In trend, blood loss was less in the MAR-VIVO-107 group (54.3 ± 34.9 vs 105.5 ± 65.8 g, P = .222). Aspartate transaminase levels were significantly lower in the MAR-VIVO-107 group when compared with the Tisseel group (39.0 ± 10.0 vs 72.4 ± 23.4 U/L, P = .0459). CONCLUSION: The efficacy of MAR-VIVO-107 and comparable performance to the gold standard fibrin have been shown under pre-clinical conditions. MAR-VIVO-107 permits hemorrhage control within seconds, even in wet environment.

[A Case of Pancreatic Cancer with Multiple Lymph Node Swelling Caused by Sarcoidosis].

A 69-year-old woman who was identified the tumor of the pancreas tail by CT scan for postoperative inspection of breast cancer. Pancreas tail cancer with para-aortic lymph node metastases was diagnosed by close inspection. She consulted a different hospital to receive their second opinion. She was diagnosed of sarcoidosis from points with lymphadenopathy in hilar region and para-aorta for 3 years and uveitis. The patient was referred to our institution for treatment. We performed distal pancreatectomy in March, 2014. No.16 lymph nodes were cancer-negative, but lymph nodes around the pancreas were cancer positive. Abdominal CT, 9 months after surgery, showed lymph node swelling. We recommended a definitive diagnosis by EUS-FNA, but she refused the inspection. She was checked by CT scan regularly afterwards and is alive without recurrence 39 months after the operation. Diagnosis for lymph node metastases is difficult for a malignant tumor when the sarcoidosis coexisted.

Proposal of a new staging system for intrahepatic cholangiocarcinoma: Analysis of surgical patients from a nationwide survey of the Liver Cancer Study Group of Japan.

BACKGROUND: In the current American Joint Committee on Cancer/International Union Against Cancer staging system (seventh edition) for intrahepatic cholangiocarcinoma (ICC), tumor size was excluded, and periductal invasion was added as a new tumor classification-defining factor. The objective of the current report was to propose a new staging system for ICC that would be better for stratifying the survival of patients based on data from the nationwide Liver Cancer Study Group of Japan database. METHODS: Of 756 patients who underwent surgical resection for ICC between 2000 and 2005, multivariate analyses of the clinicopathologic factors of 419 patients who had complete data sets were performed to elucidate relevant factors for inclusion in a new tumor classification and staging system. RESULTS: Overall survival data were best stratified using a cutoff value of 2 cm using a minimal P value approach to discriminate patient survival. The 5-year survival rate of 15 patients who had ICC measuring ≤ 2 cm in greatest dimension without lymph node metastasis or vascular invasion was 100%, and this cohort was defined as T1. Multivariate analysis of prognostic factors for 267 patients with lymph node-negative and metastasis-negative (N0M0) disease indicated that the number of tumors, the presence arterial invasion, and the presence major biliary invasion were independent and significant prognostic factors. The proposed new system, which included tumor number, tumor size, arterial invasion, and major biliary invasion for tumor classification, provided good stratification of overall patient survival according to disease stage. Macroscopic periductal invasion was associated with major biliary invasion and an inferior prognosis. CONCLUSIONS: The proposed new staging system, which includes a tumor cutoff size of 2 cm and major biliary invasion, may be useful for assigning patients to surgery.

Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion.

BACKGROUND & AIMS: The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey. METHODS: We analyzed data for 6474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2093 patients who underwent LR and 4381 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 1058 patients (66.1% of the LR group). RESULTS: In the Child-Pugh A patients, the median survival time (MST) in the LR group was 1.77years longer than that in the non-LR group (2.87years vs. 1.10years; p<0.001) and 0.88years longer than that in the non-LR group (2.45years vs. 1.57years; p<0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of age, etiology of HCC, tumor marker elevation, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative 90-day mortality rate was 3.7% (68 patients). CONCLUSIONS: As long as the PVTT is limited to the first-order branch, LR is associated with a longer survival outcome than non-surgical treatment. LAY SUMMARY: The presence of portal vein tumor thrombosis in patients with hepatocellular carcinoma is regarded as indicating an advanced stage, and liver resection is not recommended. We performed a multicenter, nationwide study to assess the survival benefit of liver resection in hepatocellular carcinoma patients with portal vein tumor thrombosis using propensity score-based matching. As long as the portal vein tumor thrombosis is limited to the first-order branch, liver resection is associated with a longer survival outcome than non-surgical treatment.

Comparative clinicopathological study of biliary intraductal papillary neoplasms and papillary cholangiocarcinomas.

AIMS: The aim of this study was to achieve a better definition of intraductal papillary neoplasms of the bile duct (IPNBs). METHODS AND RESULTS: Biliary tumours that showed predominantly intraductal papillary growth were provisionally classified as IPNBs (n = 25) and papillary cholangiocarcinomas (n = 27). IPNB was defined as a neoplasm that is confined to the epithelium or is regularly arranged in a high-papillary architecture along thin fibrovascular stalks, whereas the term 'papillary cholangiocarcinoma' was used for tumours with more complex papillary structures (e.g. irregular papillary branching or mixed with solid-tubular growth). In our consecutive cohort of biliary neoplasms, 5% were classified as IPNBs, and 10% as papillary cholangiocarcinomas. IPNBs differed from papillary cholangiocarcinomas by less advanced invasion, gross mucin overproduction (72% versus 7%), and their prevalent location (84% of IPNBs in intrahepatic/hilar ducts; 70% of papillary cholangiocarcinomas in extrahepatic ducts). Gastric-type and oncocytic-type tumours were only detected in IPNBs. Expression of mucin core proteins and cytokeratin 20 significantly differed between the two groups. KRAS and GNAS were wild-type genotypes in all but one case of KRAS-mutated IPNB. Patients with IPNB had better recurrence-free survival than those with papillary cholangiocarcinoma (P = 0.007). In multivariate analysis, in which several other prognostic factors (e.g. stromal invasion and lymph node metastasis) were applied, the classification of the two papillary tumours was an independent prognostic factor (P = 0.040). CONCLUSIONS: Given the significant contrast in clinicopathological features between IPNBs and papillary cholangiocarcinomas, it may be more appropriate to use the diagnostic term 'IPNB' for selected tumours that show regular papillary growth, separately from papillary cholangiocarcinomas.

Recommendation of treatment strategy for postpancreatectomy hemorrhage: Lessons from a single-center experience in 35 patients.

BACKGROUND: Postpancreatectomy hemorrhage (PPH) is a life-threatening complication of pancreatic surgery. The shift from surgical to radiological intervention was recently reported in retrospective cohort studies, but it has remained controversial as to which emergent intervention provides optimal management. METHODS: All 553 patients who underwent standard pancreatic resection at Kobe University Hospital between January 2003 and December 2013 were included. Patient data and complication data were identified from a prospective database. RESULTS: The overall incidence of PPH was 6% (35 of 553 patients). Ten patients underwent endoscopic intervention or observation monitoring, or suffered hemorrhagic sudden death. Among the remaining 25 PPH patients, primary surgical intervention was successful in the 6 hemodynamically unstable PPH patients. Primary radiological intervention could successfully stop the bleeding in 15 of the 17 patients with late-PPH. Nine patients who had bleeding from the hepatic artery after pancreaticoduodenectomy were rescued by endovascular embolization of the artery-trunk. The in-hospital mortality of PPH was 20% (7 of 35). Four of the 5 PPH patients who died following any intervention eventually died due to the other complications associated with prolonged pancreatic fistula. CONCLUSIONS: The leading treatment has been radiological intervention. Endovascular embolization of the hepatic artery-trunk can be securely performed only if blood flow to the liver by an alternate route is confirmed. To reduce mortality of PPH patients, it is necessary to prevent other complications associated with pancreatic fistula following hemostasis. Proactive surgical intervention such as abscess drainage or remnant pancreatectomy is a key consideration.