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Among the variations of the right hepatic artery (RHA), the identification of an aberrant RHA arising from the gastroduodenal artery (GDA) is vital for avoiding damage to the RHA during surgery, since ligation of the GDA is necessary during pancreaticoduodenectomy (PD). However, this variation is not frequently reported. The purpose of this study was to focus on an aberrant RHA arising from the GDA, which was not noted in the classifications reported by Michels and Hiatt. A total of 574 patients undergoing a PD between Jan 2001 and Dec 2015 at a tertiary care hospital in Switzerland (n = 366) and between Jan 2009 and May 2015 at a hospital in Japan (n = 208) were included in the analysis. Of these, preoperative CT angiography or/and MRI angiography findings were available for 532 patients. We retrospectively analyzed the hepatic artery variations, patient demographics, and surgical outcomes. Among the 532 patients who received a PD, an RHA originating from the GDA was observed in 19 cases (3.5%). Eleven patients (2.1%) had both an aberrant RHA and an aberrant left hepatic artery (LHA) (Hiatt Type 4). Six patients (1.2%) had a replaced CHA arising from the SMA (Hiatt Type 5). We could, therefore, correctly identify the aberration in all cases. We observed rarely reported but important aberrant RHA variations arising from the GDA. To prevent injury during PD in patients with this type of aberrant RHA, intensive preparations using CT and/or MRI imaging before surgery and intraoperative liver Doppler ultrasonography are considered to be essential.

Major hepatectomy in patients with insufficient future liver remnant (FLR) volume and impaired liver functional reserve has considerable risks for posthepatectomy liver failure (PHLF). The patient was a male in his 70s with an intrahepatic cholangiocarcinoma in left hemiliver, involving the middle hepatic vein (MHV). Although FLR volume after left hemihepatectomy was estimated to be 64.4% of the total liver volume, an indocyanine green retention rate at 15 min (ICG-R15) value was 24.2%, thus the patient underwent left portal vein embolization. The FLR volume increased to 71.3%; however, the noncongestive FLR volume was re-estimated as 45.8% after resection of the MHV, the ICG-R15 value was 29.0%, and ICG-Krem was calculated as 0.037. We performed partial rescue Associating Liver Partition and Portal vein occlusion for Staged hepatectomy (ALPPS) for left hemihepatectomy with the MHV reconstruction. On the first stage, partial liver partition was done along Rex-Cantlie’s line, preserving the MHV and sacrificing the remaining branches to segment 8. The FLR volume increased to 77.4% on day 14. The ICG-R15 value was 29.6%, but ICG-Krem after MHV reconstruction was estimated to be 0.059. The second-stage operation on day 21 was left hemihepatectomy with the MHV reconstruction using the left superficial femoral vein graft. The usage of rescue partial ALPPS may contribute to preventing PHLF by introducing occlusion of the portal and/or venous branches in the left hemiliver before curative hepatectomy.

Background To clarify whether double-volume peritoneal lavage can decrease the risk of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy. Materials and Methods Forty-nine patients who underwent pancreaticoduodenectomy and intraoperative peritoneal lavage using 6000 mL of saline before abdominal closure were studied retrospectively. Bacterial cultures of the lavage fluid were taken twice, after irrigation using 3000 mL of saline and then after an additional 3000 mL of saline. Bacterial culture of the drainage fluid was taken on day 1, and the relationship between the results of bacterial cultures and clinically relevant postoperative pancreatic fistula was examined. Results Double amount of peritoneal lavage significantly decreased the incidence of positive bacterial cultures than single amount of peritoneal lavage (45% vs. 29%, P < .05). Multivariate analysis showed that positive bacterial culture of drainage fluid on day 1 and main pancreatic duct size (Discussion A positive bacterial culture on day 1 is an independent risk factor for clinically relevant postoperative pancreatic fistula during pancreaticoduodenectomy. Double-volume intraperitoneal lavage may be effective for reducing the incidence of clinically relevant postoperative pancreatic fistula.

OBJECTIVE To assess the clinical impact of a no-drain policy after hepatic resection. SUMMARY OF BACKGROUND DATA Previous randomized controlled trials addressing no-drain policy after hepatic resection seem inconclusive because they did not adopt appropriate study design to validate its true clinical impact. METHODS This unblinded, randomized controlled trial was done at 7 Japanese institutions. Patients undergoing hepatic resection without biliary reconstruction were randomized to either D group or ND group. When the risk of postoperative bile leakage or hemorrhage were considered high, the patients were excluded during the operation. Primary endpoint was the postoperative complication of C-D grade 3 or higher within 90 postoperative days. A noninferiority of ND group to D group was assessed, and if it was confirmed, a superiority was assessed. RESULTS Between May 2015 and July 2017, a total of 400 patients were finally included in the per-protocol set analysis: 199 patients in D group and 201 patients in ND group. Intraoperatively, 37 patients were excluded from the final enrollment because of high risk of bile leakage or hemorrhage. Postoperative complication rate of C-D grade 3 or higher was 8.0% (16/199) in the D group and 2.5% (5/201) in the ND group. The risk difference was -5.5% (95% confidence interval: -9.9% to -1.2%) and fulfilled the prescribed noninferiority margin of 4%. No postoperative mortality was experienced in both groups. Bile leakage was diagnosed in 8.0% (16/199) of the D group and none in the ND group (P < 0.001). In none of the subgroups classified based on 8 potentially relevant factors, drain placement was favored in terms of C-D grade 3 or higher complication. CONCLUSIONS Drains should not be placed after uncomplicated hepatic resections.

Providing home enteral nutrition (HEN) might prevent further deterioration of nutritional status and reduce complication risk after very invasive abdominal surgery. The aim of this study was to assess the effect of HEN after pancreaticoduodenectomy (PD).Between January 2013 and July 2016, 150 consecutive patients underwent PD. All patients received postoperative enteral nutrition until discharge. HEN (400 or 800 kcal/d) was introduced in March 2015 for patients with reduced food intake (daily,15 kcal/kg ideal body weight) at discharge (HEN group). Patients with low intake at discharge treated before March 2015 were considered historical controls (non-HEN group). All patients received postoperative enteral nutrition until discharge. Primary outcomes measures included morbidity rate and nutritional status including body weight and blood examination from discharge until postoperative day (POD) 90.The HEN and non-HEN groups included 24 and 39 patients, respectively. HEN was provided for a median of 68 d (range, 21-90 d) and two patients (8.4%) developed tube obstruction during HEN. The HEN group showed significantly lower rate of morbidity of Clavien-Dindo grade II from discharge to POD 90 or higher (4 of 24, 16.7% versus 17 of 39, 46.1%; P = 0.031) and significantly higher rate of increase in body weight (median: 4.9% versus -4%; P = 0.003), serum albumin levels on POD 90 (median: 3.8 versus 3.5 g/dL; P = 0.020), and prognostic nutritional index (median: 48.5 versus 42.5; P = 0.012). Multivariate logistic analysis demonstrated that body weight at discharge (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.53-0.97) and not receiving HEN (OR, 3.86; 95% CI, 1.81-15.2) were prognostic factors for morbidity after discharge.HEN is safe and may reduce postdischarge morbidity and improve nutritional status after PD.

Exocrine pancreatic insufficiency, caused by disease-induced loss of pancreatic exocrine cells, may be treated through regenerative stem cell technologies that facilitate the production of pancreatic exocrine cells from induced pluripotent stem cells (iPSCs). However, delivering the digestive enzymes produced in the transplanted cells to the gastrointestinal tract remains a challenge. To generate an allogenic transplantation rat model, minced pancreas was transplanted into the gastric submucosal space with ablation of muscularis mucosa. In the allogenic transplantation, transplanted pancreatic cells were engrafted. Elevated amylase was detected in gastric juice, while transplanted cells disappeared through auto-digestion when the muscularis mucosa was not eliminated. Human iPSCs were differentiated into pancreatic exocrine cells by stage-specific treatment with growth factors and chemical compounds, and the differentiated pancreatic cells were implanted into the gastric submucosal space of nude rats. The transplanted cells were engrafted, and amylase was detected in the gastric juice in some cases. These findings suggest that transplantation of pancreatic exocrine cells into the gastric submucosal space with muscularis mucosa elimination will contribute to a regenerative approach for pancreatic exocrine insufficiency.

Benign portal vein stenosis is a rare complication following pancreaticoduodenectomy. Because a direct surgical approach to the portal vein is difficult due to severe adhesions following pancreaticoduodenectomy, portal vein stent placement is considered a good treatment option. Herein, we report 3 cases of severe portal vein stenosis following pancreaticoduodenectomy that were treated with portal venous stent placement in a hybrid operating room, combining a conventional operating room with an angiography suite. High-resolution images on digital subtraction angiography provide better contrast and support accurate stent placement compared to using a mobile C-arm.

Despite the major advances in analgesic techniques, pain relief in coughing after abdominal surgery remains challenging. Cough-related pain causes postoperative respiratory complications by impairing sputum clearance; nevertheless, an effective technique to abolish it is not yet available. We devised the bilateral flank compression (BFC) maneuver, in which the flanks are compressed medially using both hands. We conducted a prospective, single-center, single arm, nonrandomized, open-label, interventional trial, to investigate whether the BFC maneuver relieves cough-related pain after abdominal surgery and examined the efficacy of this maneuver in relation to patient characteristics and surgical factors.Participants were patients who underwent gastroenterologic surgery (except for open inguinal hernia repair) at the Department of Surgery, Kyorin University School of Medicine. We evaluated postoperative pain, from postoperative days (PODs) 1 to 7, on coughing, with and without the BFC maneuver, using the Prince Henry pain scale.We finally analyzed 514 patients. On each of the first 7 PODs, the BFC maneuver significantly relieved cough-related pain, especially on POD1; (the mean pain scores [standard deviation] with and without the BFC maneuver were 0.98 [1.030] vs 1.63 [1.112] points, p0.0001). On each POD, more patients were free of cough-related pain with than without the BFC maneuver, with the most marked difference on POD7 (52.0% [208/400] vs 16.8% [67/400], p0.0001).The BFC maneuver relieves cough-related pain after abdominal surgery and may help prevent of postoperative pulmonary complications.

Background Left lateral sectionectomy (LLS) is frequently performed for surgical treatment of hepatocellular carcinoma (HCC) located in the left lateral section. However, no reports have described liver resection for such HCCs using a parenchyma-sparing strategy involving anatomic resection (AR) of segment II (S2 AR) or segment III (S3 AR). Methods From 1994 to 2014, patients who underwent LLS and S2 AR or S3 AR for HCC were included in the analysis. Short- and long-term outcomes and pre- and postoperative LV were assessed. Results Of the 89 patients selected, 49 underwent LLS (LLS group) and 40 underwent S2 AR and S3 AR (S2/S3 AR group). The postoperative LV was not significantly smaller than the preoperative LV in the S2/S3 AR group (p = 0.114), whereas the postoperative LV was significantly smaller in the LLS group (p = 0.019). The overall survival (OS) and recurrence free survival (RFS) rates were not significantly different between the groups (OS, p = 0.056; RFS, p = 0.102). Conclusions Parenchyma-sparing liver resection for HCC in the left lateral section is associated with better postoperative LV recovery than LLS with similar oncological outcomes. S2/S3 AR can be a reasonable therapeutic option when LLS results in the removal of more parenchyma than necessary.

Pancreatic masses consisting of lipomatous components clinically include lipoma, liposarcoma, lipomatous pseudohypertrophy of the pancreas, fat-containing neoplasms such as perivascular epithelioid cell tumor, and malignant neoplasm with lipoid degeneration. We present pancreatic lipomatous hamartoma, which has not been reported hitherto. A solid pancreatic mass was detected from a computed tomographic scan check-up in each of 3 cases of Japanese men. Macroscopically, well-demarcated solid lipomatous masses were detected at the uncus, body, and tail of the pancreas, respectively. Microscopically, the masses predominantly consisted of mature adipocytes with no atypia, but contained characteristics components of pancreatic hamartoma, such as small ducts, a well-preserved acinar structure, and/or fibrous stroma. On the basis of the unique features, lack of islets and absence of periductal elastic fibers, these tumors are a distinct variant of pancreatic hamartoma. Furthermore, high-mobility group AT-hook 2 expression in the fibro-adipocytes of this tumor indicated that these cells are an integral component of the pancreatic lipomatous hamartoma. Consequently, the unique tumors described herein are pancreatic lipomatous hamartoma, which must be discriminated from other lipomatous lesions of the pancreas.

Repeated resection is known to prolong survival, with an acceptable morbidity rate, in patients with hepatocellular carcinoma. However, little is known about the effect of repeated liver resection on postoperative liver regeneration and liver function. The aim of this study is to determine the impact of repeated liver resections on the postoperative liver regeneration rate and liver function. A total of 71 patients, who had undergone more than three liver resections for hepatocellular carcinoma between May 2001 and December 2013 at a tertiary care hospital in Japan, were included in the analysis. Among them, CT-volumetric data for the first, second, third, and fourth or more resections were available for 36, 49, 53, and 24 patients. We analyzed the regeneration index (RI) defined as the postoperative TLV/preoperative TLV × 100 was calculated after each operation to measure the degree of regeneration. Liver function was evaluated using the indocyanine green retention rate at 15 min (ICG-R15). No significant differences in RI were observed among the first, second, and third or more liver resection groups. No significant difference in the ICG R15 value was seen between the first liver resection group and the second or more liver resection group (P = 0.75). However, a significant difference in the RI was observed when the 1 segmentectomy or less liver resection group (median [range] RI 98.1 [72.9–119.9]) was compared with the 2 or more segmentectomy group (median [range] RI 90.5 [62.6–113.6]) (P = 0.005). The regeneration process is maintained after as many as four repeated resections. Patients with sustained liver function can safely undergo repeated liver resections for recurrences of HCC.

Background The aim of this study was to evaluate the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with preoperative renal dysfunction (RD). Methods Data from 735 patients undergoing primary liver resection for HCC between 2002 and 2014 were analyzed. Short- and long-term outcomes were compared between the RD group, defined by a preoperative estimated glomerular filtration rate of

We aimed to investigate the diagnostic accuracy of multidetector-row computed tomography (MDCT), mapping biopsy, and other imaging modalities to predict the longitudinal extension and depth of invasion of extrahepatic cholangiocarcinoma at possible surgical ductal margins. Of 102 patients with surgical resection of extrahepatic cholangiocarcinoma between January 2010 and October 2015, 32 evaluated by multidetector-row computed tomography (MDCT) performed before biliary drainage and mapping biopsy were enrolled. Mapping biopsies were performed at 74 sites to determine the resection point of the bile duct (at 74 possible surgical ductal margins). Diagnostic accuracy was evaluated by histopathology. The diagnostic accuracy of MDCT for longitudinal cancer spread was 79.7%, that of biopsy was 73.0%, and combining the two modalities showed highest accuracy (83.8%). The depth of tumor invasion could be predicted by combination of the ductal wall thickness and contrast enhancement on MDCT, that is, at 11 of 13 sites (84.6%) with submucosal invasion, ductal wall thickness was > 2.5 mm with high contrast enhancement. MDCT demonstrated highest accuracy of diagnosing longitudinal extension at possible surgical ductal margins in patients with extrahepatic cholangiocarcinoma. The depth of tumor invasion could be predicted by ductal wall thickness and contrast enhancement of MDCT.

A 68-year-old male who had undergone low anterior resection for primary rectal cancer 19 months ago presented with multiple CLM at Couinaud's segments IV, V, and VIII. There was no apparent macroscopic intrabiliary growth on preoperative computed tomography and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). However, the hepatobiliary phase of EOB-MRI revealed peritumoral low signal intensity in lesions in segments V and VIII, which indicates vascular invasion around hepatocellular carcinoma. Contrast-enhanced intraoperative ultrasound (CE-IOUS) clearly determined the extent of macroscopic glissonean growth from lesions in segments V and VIII, and more extensive resection was performed than was planned. Analysis of the resected specimens from segments V and VIII confirmed the presence of macroscopic intrabiliary growth with microscopic portal vein invasion. All three CLM were histopathologically diagnosed as well-to-moderately differentiated adenocarcinoma, and R0 resection was verified. Postoperative recovery was uneventful, and the patient was alive without evidence of recurrence 12 months after hepatic resection. CE-IOUS should be considered at the time of CLM resection, as it might enable more accurate detection of macroscopic intrabiliary growth of CLM, and enable resection with safer margins.

BACKGROUND Little is known about the anatomy of the jejunal veins (JVs) flowing into the superior mesenteric vein (SMV), and whether they can be safely divided during pancreaticoduodenectomy. METHODS Computed tomography was used to review the jejunal branches off the superior mesenteric artery (SMA) and into the SMV in 123 consecutive patients. The common trunk of the JVs (jejunal venous trunk, JVT) was classified as ventral or dorsal to the SMA. RESULTS The first JVT involved multiple JVs in 108 (87.8%) cases. The first JVT diameter (≥7 or

The salvage liver transplantation (LT) strategy was conceived for initially resectable and transplantable hepatocellular carcinoma (HCC) to obviate upfront transplantation, with salvage LT in the case of recurrence. The longterm outcomes of a second resection for recurrent HCC have improved. The aim of this study was to perform an intention-to-treat analysis of overall survival (OS) comparing these 2 strategies for initially resectable and transplantable recurrent HCC. From 1994 to 2011, 391 patients with HCC who underwent salvage LT (n = 77) or a second resection (n = 314) were analyzed. Of 77 patients in the salvage LT group, 21 presented with resectable and transplantable recurrent HCC and 18 underwent transplantation. Of 314 patients in the second resection group, 81 presented with resectable and transplantable recurrent HCC and 81 underwent a second resection. The 5-year intention-to-treat OS rates, calculated from the time of primary hepatectomy, were comparable between the 2 strategies (72% for salvage transplantation versus 77% for second resection; P = 0.57). In patients who completed the salvage LT or second resection procedure, the 5-year OS rates, calculated from the time of the second surgery, were comparable between the 2 strategies (71% versus 71%; P = 0.99). The 5-year disease-free survival (DFS) rates were 72% following transplantation and 18% following the second resection (P

Background and Objectives To clarify the detectability of gadolinium ethoxybenzyl diethylene-triamine pantaacetic acid enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced intraoperative-ultrasonography (CE-IOUS) for residual disease in disappearing colorectal liver metastases (DLMs) and to seek a better management for DLMs. Methods Eighty-two patients who underwent hepatectomy after chemotherapy for colorectal liver metastases were retrospectively reviewed. Lesions which disappear on post-chemotherapy contrast-enhance CT were defined as DLMs. All the patients underwent EOB-MRI and CE-IOUS. With pathologic evaluation for resected specimens and clinical observation of anatomically corresponding site for non-resected lesions, detectability of residual disease in DLMs were estimated between these two imaging modalities. Results Twenty (18%) patients presented with 111 DLMs, and EOB-MRI and CE-IOUS identified 64 (57.6%) and 62 (55.9%), respectively. Residual disease was pathologically confirmed for 69.2% in resected specimens and clinically estimated in 33.3% for non-resected DLMs. EOB-MRI showed a higher accuracy of prediction of residual disease compared with CE-IOUS (0.90 vs 0.70). Of the 11 non-resected lesions which were undetected with CE-IOUS and regrew after surgery, 9 (81.8%) were detected on EOB-MRI. Conclusions EOB-MRI may be superior to CE-IOUS in detecting residual tumors for DLMs. Maximum attempt of resection would be needed for visualized lesions in EOB-MRI.

Background: Pancreaticoduodenectomy (PD) is performed for pancreatic ductal adenocarcinoma (PDA) located at the pancreas head/body. Non-chylous massive discharge after PD is frequently encountered and can cause a vicious cycle of complications associated with severe dehydration and protein loss. Methods: From August 2008 to June 2015, 102 patients who underwent PD for PDA were retrospectively reviewed. High non-chylous discharge was defined as postoperative daily serous discharge exceeding 10 mL/kg. Predictive factors for high non-chylous discharge were assessed using multivariable analysis. Results: Fifty-one patients (50%) developed high non-chylous discharge. Body mass index (BMI) and hemoglobin, total protein, and cholinesterase levels were significantly lower in the high-discharge group compared to the corresponding levels in the low-discharge group. The incidence of postoperative pancreatic fistula and delayed gastric emptying was significantly lower and higher in the high-discharge group than in the low-discharge group, respectively. Multivariable analysis revealed that BMI 2, hemoglobin Conclusions: Preoperative low levels of BMI and hemoglobin and intraoperative high blood loss were independent predictive factors for high non-chylous discharge. Improvement of preoperative general and nutritional condition may reduce the incidence of high non-chylous discharge.

Background Only a few studies have reported the resection and reconstruction of major hepatic veins during hepatectomy. Here we present our strategy and techniques for venous reconstruction with cryopreserved homologous veins, and describe the surgical outcome. Methods Among 2387 hepatectomy patients, 39 patients who required hepatic venous reconstruction were reviewed retrospectively. Venous reconstruction was performed to secure a non-congested liver remnant volume of at least 40% of the total liver volume. Results There was no operative mortality, and the severe morbidity rate was 5% in this series. A total of 41 veins were reconstructed; 30 with homologous veins (73.2%) and 11 with autologous veins (26.8%), with the middle hepatic vein being the most frequent (n=23, 56%). Interposition grafting was performed more often (P=0.003), the length of the venous resection was longer (P=0.007), and pathologic wall infiltration of the vein was revealed more often (P=0.002) in the homologous graft group than in the autologous graft group. The 1-, 2-, and 3-year overall patency of the reconstructed veins was 55.4%, 46.3%, and 46.3%, respectively. Conclusions Aggressive venous reconstruction during hepatectomy using cryopreserved homologous veins is a feasible option with satisfactory short-term outcomes, and may be warranted to improve operative safety. This article is protected by copyright. All rights reserved.

Background and Objectives Portal vein (PV) territory identification during liver resection may be performed using indocyanine green (ICG) fluorescence imaging technique. However, the technical details of the fluorescence staining technique have not been fully elucidated. This study was performed to demonstrate the technical details of PV territory identification using fluorescence imaging and evaluates the short-term outcomes. Methods From 2011 to 2015, 105 underwent liver resection at the University of Tokyo Hospital with one of the following fluorescence staining techniques by transhepatic PV injection or intravenous injection of ICG: single staining (n = 36), multiple staining (n = 31), counterstaining (n = 22), negative staining (n = 13), or paradoxical negative staining (n = 3). Results The PV territory was identified as a region with fluorescence or a defect of fluorescence using one of the five staining techniques. ICG was administered by transhepatic PV injection in all but the negative staining technique, which employed intravenous injection. No adverse events associated with the ICG administration occurred. The mortality, postoperative total morbidity, and the major complication (Clavien-Dindo grade ≥III) rates were 0.0%, 14.3%, and 7.6%. Conclusions We have demonstrated the technical details of five types of fluorescence staining techniques. These techniques are safe to perform and facilitate clear visualization of the PV territory in real time, enhancing the efficacy of anatomical removal of such territories.

Aims: To clarify the clinical impact, risk factors, and preventive methods for surgical site infection (SSI) after hepatectomy for hepatocellular carcinoma (HCC). Methods: We included 879 consecutive patients who underwent hepatectomy for HCC between 2002 and 2011. Univariate and multivariate analyses were conducted to identify the risk factors for incisional and organ/space SSIs. ORs and 95% CIs are reported. Results: The incidences of incisional and organ/space SSIs were 24 (2.7%) and 73 (8.3%), respectively. High body mass index, multiple resections, and organ/space SSI were associated with incisional SSIs, while repeat hepatectomy (OR 2.14, 95% CI 1.27-3.60), ascites (OR 2.97, 95% CI 1.55-5.48), and bile leakage (OR 4.77, 95% CI 2.77-8.11) were independent risk factors for organ/space SSI. Among the cases with bile leakage, lower rates of organ/space SSIs tended to be observed in patients with cystic duct tubes than in patients without such tubes (13.2 vs. 26.5%, p = 0.157). Retrograde drain infections increased when drain placement was prolonged for more than 4 postoperative days. Conclusion: Bile leakage was associated with the greatest risk of organ/space SSI after hepatectomy for HCC. Cystic duct tubes might be useful for preventing bile leakage and subsequent organ/space SSI after procedures that extensively expose Glissonean pedicles.

A potentially favorable effect of chemotherapy on the incidence of micrometastases has been reported in patients with colorectal liver metastases (CLMs); however, the actual influence of chemotherapy on the distribution of micrometastases and surgical curability remains unclear.The clinical impact of preoperative chemotherapy on the incidence and distribution of micrometastases was assessed in 191 patients with 357 CLM nodules. Potential radiologic measures for predicting the extent of microscopic cancer spread and surgical curability were then sought among the size-based and non-size-based radiologic response criteria.Multivariate analysis estimated a reduced incidence of micrometastases in patients receiving preoperative chemotherapy (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.26-0.76, p = 0.003). Furthermore, the addition of biologic agents to the preoperative chemotherapy regimen was correlated with a reduced incidence of microscopic cancer spread beyond a width of 1 mm from the margin of the main tumor (OR 0.28, 95% CI 0.11-0.74, p = 0.010 for bevacizumab; and OR 0.29, 95% CI 0.09-0.99, p = 0.048 for anti-epidermal growth factor receptor antibody). Receiver operating characteristic analyses revealed that the computed tomography (CT) morphologic response showed a moderate predictive power for the distribution of micrometastases, with an area under the curve of 0.687, while size-based response criteria were not reliable for estimating the extent of microscopic cancer spread.Notwithstanding the potential selection of patients after preoperative chemotherapy, the incidence and distribution of micrometastases may be reduced by preoperative chemotherapy. CT morphologic response may be a reliable predictor of both the degree of microscopic cancer spread and the curability of surgery.

Background There are several techniques for reconstructing the portal vein-superior mesenteric vein during pancreatoduodenectomy. The aim of the present study was to present our results with portal vein-superior mesenteric vein reconstruction using cryopreserved homologous veins during pancreatoduodenectomy for patients with pancreatic head cancer. Methods Patients who underwent pancreatoduodenectomy for pancreatic head cancer were reviewed retrospectively. In patients with portal vein-superior mesenteric vein resection, the detailed method of reconstruction and clinical outcomes were reviewed. Clinical characteristics, patient survival, and portal vein-superior mesenteric vein patency were compared between those with and without homologous vein grafts. Factors affecting the patency of reconstructed veins were assessed by univariate analysis. Results Among 144 patients undergoing pancreatoduodenectomy, portal vein-superior mesenteric vein resection was performed in 36 patients (25%); 18 (50%) underwent reconstruction with homologous veins, and the other 18 (50%) underwent reconstruction without homologous veins. The extent of portal vein-superior mesenteric vein involvement, operative time, duration of clamping of portal vein-superior mesenteric vein, intraoperative blood loss, and length of the venous resection were greater ( P ≤ .013 each) in those with homologous vein grafts. There was no significant difference in postoperative morbidity/mortality, patient survival, or portal vein-superior mesenteric vein patency. The 1- and 2-year overall patency of portal vein-superior mesenteric vein was 76% and 71%, respectively, while the 2-year patencies were 67% and 67% in those with homologous veins and 87% and 73% in those without homologous veins without difference between the groups. Circumferential resection and pathologic portal vein-superior mesenteric vein involvement were associated with the patency of the reconstructed vein ( P = .002 and P = .028, resp). Conclusion Use of homologous venous grafts for portal vein-superior mesenteric vein reconstruction are feasible alternatives during pancreatoduodenectomy for advanced pancreatic head cancer.

Aims BAP1 and PBRM1 expression loss has been observed in multiple cancers, including intrahepatic cholangiocarcinoma (ICC). We investigated BAP1 and PBRM1 expression in ICC using immunohistochemistry, and analyzed its association with clinicopathological and genetic features, including two histologic subtypes. Methods and results Whole-section slides of 108 consecutive primary ICC cases were immunostained against BAP1 and PBRM1. Complete loss of BAP1 and PBRM1 was observed in 21 (19.4%) and 25 (23.1%) cases, respectively, and partial loss was identified in 4 (3.7%) and 9 (8.4%) cases. In all cases, normal bile ducts were strongly and diffusely positive for both BAP1 and PBRM1. ICC with BAP1 loss showed lower serum CA19-9 levels, less perineural invasion, rare mucin production, weaker immunoreactivity against S-100P, and stronger immunoreactivity against N-cadherin and NCAM. IDH mutations were identified more frequently in ICCs with BAP1 loss. All ICC with BAP1 loss corresponded to small-duct-type ICC. Multivariate Cox regression analysis showed that BAP1 loss was an independent prognostic factor for both overall and recurrence-free survival (P < 0.05). PBRM1 loss, on the other hand, was found in both small-duct-type and large-duct-type ICC, and was not significantly associated with any specific characteristics, including prognosis. Conclusion BAP1 and PBRM1 loss is frequently seen in ICC. ICC with BAP1 loss shares features of small-duct-type ICC. This article is protected by copyright. All rights reserved.

Two-stage hepatectomy combined with in-situ splitting of the liver and concomitant portal ligation during the first stage could facilitate more rapid hypertrophy of the future liver remnant (FLR) than with conventional portal vein embolization (PVE).1,2 This innovative hepatectomy, named Associating

Intrahepatic cholangiocarcinoma (ICC) is an extremely aggressive carcinoma. Useful predictors for the patients' prognosis after surgery have not been fully established. From the University of Tokyo Hospital pathology archives, we reviewed 107 cases of ICC, 54 cases of perihilar cholangiocarcinoma, and 40 cases of extrahepatic cholangiocarcinoma (ECC); we also investigated the significance of tumor budding in ICC, in comparison with perihilar cholangiocarcinoma and ECC. The tumor-budding frequencies were different by tumor location: 40.2% (43/107) in ICC, 70.4% (38/54) in perihilar cholangiocarcinoma, and 60.0% (24/40) in ECC. Tumor budding in ICC was associated with many pathologic indicators associated with invasion, such as major vascular invasion (P=0.012) and Union for International Cancer Control stage (P=0.007). Univariate and multivariate Cox regression analyses revealed tumor budding as a powerful prognostic factor for both recurrence-free survival (RFS) and overall survival (OS) in ICC by univariate (RFS: hazard ratio [HR]: 2.666; 95% confidence interval [CI]: 1.517-4.683, OS: HR: 4.206; 95% CI: 2.447-7.230) and by multivariate analyses (RFS: HR: 3.038; 95% CI: 1.591-5.973, OS: HR: 4.547, 95% CI: 2.348-8.805). Tumor budding was also a significant prognostic factor of perihilar cholangiocarcinoma, but not of ECC. When ICC was divided into 2 subtypes, type 1 (hilar) and type 2 (peripheral), tumor budding was the strong prognostic factor in type 2 ICC, but not in type 1 ICC, suggesting that some differences in biological behavior exist between type 1 ICC and perihilar cholangiocarcinoma. Tumor budding is prognostically important in ICC, and its pathogenetic role in biliary tract carcinomas might be different by anatomic location.

Previous studies have identified 2 clinically significant morphologic subtypes of intrahepatic cholangiocarcinoma (ICC) on the basis of anatomic location and/or histologic appearances. Recognizing that these classification schemes are not always applicable practically, this study aimed to establish a novel classification system based on mucin productivity and immunophenotype and to determine the rationale of this classification by examining the clinicopathologic and genetic characteristics of the 2 subtypes defined by this method. We retrospectively investigated 102 consecutive ICC cases and classified them on the basis of mucin productivity and immunophenotype (S100P, N-cadherin, and NCAM). We found that 42 and 56 cases were classified as type 1 and type 2 ICCs, respectively, and only 4 cases were of indeterminate type. Type 1 ICC, generally characterized by mucin production and diffuse immunoreactivity to S100P, arose less frequently in chronic liver diseases and showed higher levels of serum CEA and CA 19-9 than did type 2 ICC, which generally showed little mucin production and exhibited immunoreactivity to N-cadherin and/or NCAM. Type 1 ICC was characterized by several pathologic features, including higher frequencies of perineural invasion and lymph node metastasis. Although the log-rank test demonstrated that type 1 ICC had significantly worse survival, the multivariate Cox regression analysis showed no prognostic significance of this histologic subtype. Genetic analyses revealed that KRAS mutation was significantly more frequent in type 1 ICC, whereas IDH mutation and FGFR2 translocation were restricted to type 2 ICC. In conclusion, the present classification of ICC based on mucin productivity and immunophenotype identified 2 subtypes with clinicopathologic significance.

// Keisuke Yamamoto 1 , Keisuke Tateishi 1 , Yotaro Kudo 1 , Mayumi Hoshikawa 2 , Mariko Tanaka 3 , Takuma Nakatsuka 1 , Hiroaki Fujiwara 1 , Koji Miyabayashi 1 , Ryota Takahashi 1 , Yasuo Tanaka 1 , Hideaki Ijichi 1 , Yousuke Nakai 1 , Hiroyuki Isayama 1 , Yasuyuki Morishita 3, 4 , Taku Aoki 2, 5 , Yoshihiro Sakamoto 2 , Kiyoshi Hasegawa 2 , Norihiro Kokudo 2 , Masashi Fukayama 3 , Kazuhiko Koike 1 1 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan 2 Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan 3 Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan 4 Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan 5 Second Department of Surgery, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan Correspondence to: Keisuke Tateishi, email: ktate-tky@umin.ac.jp Keywords: pancreatic ductal adenocarcinoma (PDAC), cancer-associated fibroblast (CAF), epigenetics, bromodomain and extraterminal domain (BET) proteins, JQ1 Received: March 21, 2016 Accepted: July 27, 2016 Published: August 09, 2016 ABSTRACT Inhibitors of bromodomain and extraterminal domain (BET) proteins, a family of chromatin reader proteins, have therapeutic efficacy against various malignancies. However, the detailed mechanisms underlying the anti-tumor effects in distinct tumor types remain elusive. Here, we show a novel antitumor mechanism of BET inhibition in pancreatic ductal adenocarcinoma (PDAC). We found that JQ1, a BET inhibitor, decreased desmoplastic stroma, a hallmark of PDAC, and suppressed the growth of patient-derived tumor xenografts (PDX) of PDACs. In vivo antitumor effects of JQ1 were not always associated with the JQ1 sensitivity of respective PDAC cells, and were rather dependent on the suppression of tumor-promoting activity in cancer-associated fibroblasts (CAFs). JQ1 inhibited Hedgehog and TGF-β pathways as potent regulators of CAF activation and suppressed the expression of α-SMA, extracellular matrix, cytokines, and growth factors in human primary CAFs. Consistently, conditioned media (CM) from CAFs promoted the proliferation of PDAC cells along with the activation of ERK, AKT, and STAT3 pathways, though these effects were suppressed when CM from JQ1-treated CAFs was used. Mechanistically, chromatin immunoprecipitation experiments revealed that JQ1 reduced TGF-β–dependent gene expression by disrupting the recruitment of the transcriptional machinery containing BET proteins. Finally, combination therapy with gemcitabine plus JQ1 showed greater efficacy than gemcitabine monotherapy against PDAC in vivo . Thus, our results reveal BET proteins as the critical regulators of CAF-activation and also provide evidence that stromal remodeling by epigenetic modulators can be a novel therapeutic option for PDAC.

BACKGROUND Several clinical factors are reportedly correlated with acute cellular rejection (ACR) after liver transplantation. However, the factors that determine the response to rescue therapies remain unclear. METHODS A prospective database of 413 consecutive adult patients who underwent living donor liver transplantation (LDLT) was reviewed. RESULTS Ninety-nine (24%) patients developed ACR after LDLT. A multivariate analysis revealed that a positive T-lymphocytotoxic test (odds ratio [OR], 3.85; P=.017), HLA-DR mismatch (OR, 2.99; P=.013), autoimmune disease (OR, 2.61; P=.001), and a younger recipient age (OR, 0.60 for +10 years; P

of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively. The initial doses of S-1 and oxaliplatin were fixed to 80 mg/m(2) and 100 mg/m(2), respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m(2) and oxaliplatin: 130 mg/m(2)) or level 0 (S-1: 65 mg/m(2) and oxaliplatin: 100 mg/m(2)) depending on the incidence of dose-limiting toxicity (DLT) at level 1 in six patients. Results Because DLT occurred in one among the initial six patients at level 1, the doses were increased to level 2 in the next six patients. At level 2, grade 3 leukopenia and neutropenia occurred in one (16.7 %) and two (33.3 %) patients, respectively, in the absence of non-hematological event. Because no DLT occurred at level 2, we suggest that the RD can be set to the level 2 dose. The median number of cycles delivered at RD was 8. The mean relative dose intensity of S-1 and oxaliplatin at RD was 0.90 and 0.63, respectively. Conclusion In a patient undergoing hepatectomy for CLM, 80 mg/m(2) of S-1 and 130 mg/m(2) of oxaliplatin are recommended as adjuvant therapy. A further study is required to confirm the efficacy and safety of this regimen on a larger scale.

Special care must be taken in hepatic vein reconstruction to avoid outflow block in living donor liver transplantation (LDLT) with a right liver graft. We have used cryopreserved homologous veins to reconstruct the right hepatic vein (RHV), middle hepatic vein (MHV), MHV tributaries (V5 and V8), and inferior right hepatic vein (IRHV). The reconstruction of V5, V8, and IRHV was based on the estimated congestive volume, calculated by the computed tomography volumetry, to secure the functional graft volume of 40% of the recipient standard liver volume. Among 262 right liver LDLT recipients, the number of reconstructed RHVs, MHVs, V5s, V8s, and IRHVs was 262, 48, 110, 111, and 147, respectively, and the overall patency was 95%, 100%, 36%, 58%, and 86%, respectively. Although the patency of the RHVs and MHVs was satisfactory, that of the V5s, V8s, and IRHVs was suboptimal. Patency of the IRHVs (86%, 126/147) was significantly better than that of both V5s (36%, 40/110) and V8s (58%, 64/111; P

Background Relapse is common after the resection of colorectal liver metastases (CLM); however, the optimal treatment for such recurrent disease remains uncertain. We investigated whether repeat resections for successive recurrences of CLM provide survival benefit on the postrecurrence survival. Methods We reviewed patients who underwent upfront, curative resection for CLM at our center during a 15-year period. Of these, 263 patients who had not received any other perioperative treatment for the metastases were eligible for our analysis. The recurrence-free survival (RFS 0 ) after the initial hepatic resection and after the first ( n = 108), second ( n = 43), and third ( n = 15) repeat resections for recurrent disease were assessed (RFS 1–3 ). The overall survival after the initial hepatic resection and the postrecurrence survival ( n = 198) also was assessed. Results The median RFS 0 was 0.8 years, and RFS 1 , RFS 2 , and RFS 3 were 1.3, 1.1, and 2.0 years, respectively. The hazard ratio for RFS for the first, second, and third resections versus the initial hepatic resection was 0.9 (95% confidence interval [95% CI] 0.7–1.1; P = .34), 1.00 (95% CI 0.7–1.4; P = .97), and 0.7 (95% CI 0.4–1.3; P = .29). The 5-year and 10-year OS rates were 54.6% and 42.2%, and the 5-year and 10-year postrecurrence survival was 34.3% and 28.6%, respectively. Conclusion Repeat resection in patients with recurrent disease after CLM resection is beneficial, offering the potential for cure in a small proportion of patients with recurrent disease.

The KRAS mutation status is reportedly correlated with poor survival outcome in patients with colorectal liver metastases (CLM); however, its true prognostic impact and the reason for the poor prognosis remain unclear. Data on 163 patients with a known KRAS mutation status who underwent curative resection for CLM were retrospectively reviewed. The long-term survival and site-specific incidence of recurrence were then compared between patients with a KRAS mutation (mtKRAS) and those without a mutation (wtKRAS). The mtKRAS group had a poorer 3-year disease-specific survival (DSS) rate (59.8 vs. 83.6 %, p = 0.016), 3-year recurrence-free survival (RFS) rate (0 vs. 20.2 %, p = 0.069), and median time to surgical failure (TSF) [18.8 vs. 39.7 months, p = 0.001] than the wtKRAS group. The cumulative incidences of liver recurrence and lung recurrence at 3 years were also higher in the mtKRAS group (76.2 vs. 54.7 %, p = 0.060; and 71.9 vs. 37.3 %, p

Ecotropic virus integration site 1 protein homolog (EVI1), a well-known oncogenic transcriptional factor of hematopoietic cells, contributes to pancreatic cancer oncogenicity through increased expression of KRAS. Because EVI1 was upregulated in cholangiocarcinoma by referring The Cancer Genome Atlas, we investigated the importance of EVI1 in intrahepatic cholangiocarcinoma (ICC) which has been regarded as a heterogeneous group of cancers. Immunohistochemical analysis results demonstrated that EVI1 was overexpressed in about half of ICC (53/101, 52.5%). Moreover, all intraductal papillary neoplasms of the bile duct cases expressed EVI1 regardless of histological grading and subtypes such as gastric, intestinal, pancreatobiliary, or oncocytic (20/20, 100%). EVI1-positive ICC showed higher frequencies of aggressive pathological indicators such as periductal infiltrative growth (p = 0.022), hilar invasion (p = 0.041), advanced UICC stage (p = 0.026), major vascular invasion (p = 0.026), and perineural invasion (p = 0.007) than EVI1-negative ICC. Patients with EVI1-positive ICC showed worse overall survival and recurrence-free survival in all resected cases and in curative resected cases. Recently, we proposed type 1/2 (large/small duct types) classification of ICC based on mucin productivity and immunophenotypes (S100P, N-cadherin, and NCAM). Type 1 predominantly consisted of EVI1-positive ICC (33/42 cases, 79%), and the frequency was significantly higher than type 2 (18/55 cases, 32.7%) (p

We evaluated the usefulness of fluorescence imaging using indocyanine green to identify pancreas tumors in 23 patients undergoing pancreas resection. This technique was useful in visualizing pancreas lesions during surgery, specifically, neuroendocrine tumors as fluorescence and cystic neoplasms as a fluorescence defect.

There has been a pressing need to develop optimal regimen for neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). The safety and efficacy of gemcitabine, S-1, and LV combination (GSL) therapy as NAC for borderline resectable (BR) and locally advanced (LA) PC was evaluated in this phase II study. Patients with pathologically proven BR or LA PC were enrolled and gemcitabine 1000 mg/m2 by 30-min infusion on day 1, S-1 40 mg/m2 orally twice daily, and LV 25 mg orally twice daily on days 1–7 every 2 weeks were provided, and evaluation by CT every 2 courses was performed. The primary end point was R0 resection rate, and the secondary endpoints were resection rate, response rate, adverse events, surgical outcomes, and survival. Twenty-four patients with PC (21 BR and 3 LA) were enrolled. Response rate and disease control rate of NAC were 17.4 and 87.0%. Grade 3 and 4 toxicities involved neutropenia (34.8%), anorexia (17.4%), and mucositis (17.4%). Serum CA19-9 level decreased by 52.2%. Resection rate was 60.9% after the median of 4 cycles and R0 resection rate was 76.5% in patients undergoing laparotomy. NAC-GSL is a feasible treatment option for BR and LAPC.

Right hemihepatectomy or systematic resection of segment 7 or 8 involves partial resection of the paracaval portion of the caudate lobe. However, the boundary between the caudate lobe and segment 7 or 8 remains unclear. We examined the anatomical territory of the caudate lobe with special reference to the boundary between the paracaval portion and segment 7 or 8 for precise anatomical hepatectomies. We enrolled 63 consecutive healthy donor candidates for living-donor liver transplantation from 2012 to 2014 in this study. The caudate lobe was defined according to Kumon’s subdivision system, and the boundary between the paracaval portion and segment 7 or 8 was investigated based on three-dimensional computed tomography scan images using SYNAPSE VINCENT®. The paracaval portion of the liver protruded on the liver surface underneath the right diaphragm on the ventral side of the right hepatic vein (RHV) in 10 participants (16%) and on the dorsal side of the RHV in 9 participants (14%). A branch of the RHV, the “paracaval vein,” was found in all 63 participants and ran longitudinally along the right border of the paracaval portion (n = 30, 48%) and within segment 7 (n = 16, 25%) or segment 8 (n = 17, 27%). The paracaval portion of the liver protruded on the liver surface underneath the right diaphragm in one third of our participants. The paracaval vein can be a landmark for the boundary between the caudate lobe and the segment 7 or 8 in half of the cases.

Background Some reports have shown that a significant number of patients experience recurrence, even after 5 or more years after surgery for colorectal liver metastases (CLMs). This study aimed to determine the actual cure rate and identify clinical characteristics among long-term survivors. Methods A prospectively maintained database was used to retrospectively review patients who underwent liver resection for CLM between 1994 and 2001. Results A total of 130 patients underwent liver resection for CLM with a complete 10-year follow-up. The 10-year disease-specific survival rate was 31.1%, and the survival curve reached a plateau after 10 years from the time of hepatic resection. There were 35 actual 10-year survivors. Multivariate analysis revealed that female patients and those with negative surgical margins were independent prognostic factors for disease-specific survival. Conclusion A 10-year survival following initial hepatectomy should be defined as cure.

BACKGROUND & AIMS: The standard liver volume (SLV) is widely used in liver surgery, especially for living donor liver transplantation (LDLT). All the reported formulas for SLV use body surface area or body weight, which can be influenced strongly by the general condition of the patient. METHODS: We analyzed the liver volumes of 180 Japanese donor candidates and 160 Swiss patients with normal livers to develop a new formula. The dataset was randomly divided into two subsets, the test and validation sample, stratified by race. The new formula was validated using 50 LDLT recipients. RESULTS: Without using body weight-related variables, age, thoracic width measured using computed tomography, and race independently predicted the total liver volume (TLV). A new formula: 203.3-(3.61×age)+(58.7×thoracic width)-(463.7×race [1=Asian, 0=Caucasian]), most accurately predicted the TLV in the validation dataset as compared with any other formulas. The graft volume for LDLT was correlated with the postoperative prothrombin time, and the graft volume/SLV ratio calculated using the new formula was significantly better correlated with the postoperative prothrombin time than the graft volume/SLV ratio calculated using the other formulas or the graft volume/body weight ratio. CONCLUSIONS: The new formula derived using the age, thoracic width and race predicted both the TLV in the healthy patient group and the SLV in LDLT recipients more accurately than any other previously reported formulas.

A retrospective analysis indicated that the incidence of delayed gastric emptying (DGE) was less after using a circular stapler (CS) for duodenojejunostomy than that after hand-sewn (HS) anastomosis in pylorus-preserving pancreaticoduodenectomy (PpPD). This randomized clinical trial compared the incidence of DGE postoperative after CS duodenojejunostomy with that of conventional HS anastomosis in PpPD. We randomly assigned 101 patients (age 20–80) undergoing PpPD to receive CS duodenojejunostomy (group CS, n = 50) or HS duodenojejunostomy (group HS, n = 51) in two Japanese cancer center hospitals between 2011 and 2013. The patients were stratified by institution and size of the main pancreatic duct (

Hepatocellular carcinoma (HCC) not associated with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, termed non-B non-C HCC (nBnC-HCC), is reportedly correlated with better survival outcomes than HBV- or HCV-related HCC. However, the nBnC-HCC population includes patients with a history of HBV infection possessing anti-hepatitis B core antibodies (HBcAb), and the oncologic significance of this finding remains unclear. A retrospective review of the data for 562 patients who underwent curative resection for primary HCC was performed. The clinical outcomes were compared among the following four groups: HBV group (HBsAg-positive), HCV group (HCVAb-positive), HBcAb-positive nBnC-HCC group, and pure nBnC-HCC group (negative for these viral markers). The HBcAb-positive nBnC-HCC group showed better overall survival (OS) and recurrence-free survival (RFS) rates than the HBV, HCV, and pure nBnC-HCC groups (5-year OS 89.4 vs 68.4, 62.0, and 66.2 %; P = 0.003; 5-year RFS 53.8 vs 31.4, 28.1, and 33.6 %; P = 0.01). A multivariate analysis confirmed that a history of HBV is associated with a lower risk of OS (hazard ratio [HR] 0.23; 95 % confidence interval [CI] 0.09–0.56; P = 0.001) and RFS (HR 0.45; 95 % CI 0.27–0.73; P = 0.001). The HBcAb-positive nBnC-HCC group was associated with a higher incidence of well-differentiated HCC (33 vs 15 %; P = 0.03) and lower plasma des-gamma-carboxyprothrombin concentration (72 vs 357 mAu/mL; P = 0.047) than the pure nBnC group. The subgroup of patients with a history of HBV infection may have better survival outcomes after resection of HCC than the HBV/HCV-related or pure nBnC-HCC patients.

To investigate the feasibility and prognostic benefits of third or more hepatectomy (third or more Hx) for recurrent hepatocellular carcinoma.Second hepatectomy (second Hx) has been accepted as an effective treatment of recurrent hepatocellular carcinoma after first hepatectomy (first Hx). However, the feasibility and efficacy of third or more Hx have not been adequately assessed.Data were reviewed from 1340 patients with hepatocellular carcinoma who underwent curative hepatectomy. Among them, 941, 289, and 110 underwent first Hx, second Hx, and third or more Hx, respectively. Surgical outcomes and long-term survival were compared among the groups.Surgical duration was significantly longer in third or more Hx (median, 6.4 hours) than in second Hx (median, 5.9 hours). Postoperative bile leakage and wound infection were more frequently observed in third or more Hx versus second Hx (12.5% vs 6.2%, [P = 0.04] and 2.9% vs 0.4% [P = 0.03], respectively). Three and 5-year disease-free survival rates were 36.8% and 27.1% in first Hx, 24.4% and 17.9 % in second Hx, and 26.1% and 12.8% in third or more Hx, respectively (P0.01 [first Hx vs third Hx], P = 0.95 [second Hx vs third or more Hx]). The 5-year overall survival rates from each resection were similar among the groups (65.3%, 60.5%, 68.2%, respectively). The 5- and 10-year overall survival rates from initial hepatectomy in patients who received third or more Hx were 91.4% and 75.5%, respectively.Third or more Hx is technically demanding in terms of surgical duration and morbidity compared with second Hx. However, aggressive repeat resection offers a survival similar to second Hx, leading to cumulative long-term survival from initial resection.

Despite increasing popularity of single-incision laparoscopic cholecystectomy (SILC), indication criteria assuring safety of SILC has yet to be established. In the present study, the subjects consisted of 146 consecutive patients undergoing conventional laparoscopic cholecystectomy (CLC) or SILC. SILC was indicated after excluding patients who met following criteria: age > 75 years, obesity, operative scar, cardiopulmonary diseases, acute cholecystitis, choledocholithiasis and abnormal bile duct anatomy. Thirty-four patients were excluded from the SILC candidates (moderate/high-risk CLC group). Among the 112 potential candidates, SILC was indicated for 23 patients (21%, SILC group) and the remaining 89 patients (79%) underwent CLC (low-risk CLC group). In the SILC group, operation time was longer than in the low-risk CLC group (171 [113-286] vs. 126 [72-240] min, p < 0.01), but the periods requiring painkiller was shorter. That led to reduced length of hospital stay compared to low-risk CLC group (2 [2-4] vs. 4 [2-12] days, p < 0.01). Between the low-risk CLC and moderate/high-risk CLC group, operation time was significantly longer and amount of blood loss was larger in the latter group. No complications were encountered in the SILC group. SILC can be indicated safely as far as appropriate criteria is adopted for excluding patients in whom complicated laparoscopic procedures are needed.

Effective adjuvant therapies have not been established for hepatocellular carcinoma (HCC). The study aimed to determine prognostic influence of statin against HCC recurrence after initial resection. From 2003 to 2013, 734 patients underwent initial HCC resection. Exposure to statins was defined as the use at the recommended daily dosage for > 90 days after surgery. Outcomes were compared between patients who did and did not receive statins. Of 734 patients, 31 (4.2%) received statins for dyslipidemia (statin group) and 703 (95.8%) did not (non-statin group). The proportions of hepatitis B (6.5% vs. 22.8%, P = 0.032), C (19.4% vs. 45.0%, P = 0.005), and a fibrosis score of F3-4 (16.1 % vs. 39.8%, P = 0.008) were significantly lower in the statin than non-statin group. The recurrence-free survival rate was significantly higher in the statin than non-statin group (P < 0.001), without significant difference of the overall survival rate (P = 0.142). A multivariable Cox proportional hazards model revealed that the use of statins (hazard ratio, 0.34; P = 0.005) was associated with a significantly lower risk of HCC recurrence. After one-to-two propensity score matching, the RFS rate was also significantly higher in the statin group (n = 31) than in the non-statin group (n = 62) (P = 0.008). IN CONCLUSION The statins use reduced the risk of HCC recurrence after initial resection. Statins may have protective influences on HCC recurrence in patients who undergo initial liver resection.

Background: Living-donor liver transplantation using the left liver graft with the middle hepatic vein (MHV) is a well-established procedure. Following such procedures, outflow obstruction occurs in remnant livers. However, the effects of the outflow-obstructed liver volume (LVOut-Ob), with or without venous communication development, remain unclear. The aim of the study is to investigate effects of outflow-obstructed regions by focusing on short-term outcomes and remnant liver hypertrophy in left liver procurement donors. Methods: Of 532 donors, we collected data from 119 undergoing left liver procurement with the MHV. Postoperative hepatic parameters, venous communication development, and liver hypertrophy were evaluated in two donor groups based on LVOut-Ob. Results: The left liver was procured with the MHV in 119 donors, who formed two more groups based on the median LVOut-Ob: large-outflow-obstruction (n=60; LVOut-Ob ≥263 mL) and small-outflow-obstruction (n=59; LVOut-Ob

Background Real-time tissue elastography during open hepatectomy facilitates the differential diagnosis of liver tumors by providing information on elasticity. This study investigated the utility of intraoperative real-time tissue elastography (IORTE) during laparoscopic hepatectomy (LH). Methods Between 2012 and 2014, IORTE was performed during LH for 21 hepatocellular carcinomas (HCCs), 16 adenocarcinomas and 5 other tumors in 32 patients. The elasticity images were classified into six categories according to the modified criteria on the elasticity type of liver tumors, in which type 1 tumors show more strain than the surrounding liver and type 6 tumors no strain. The concordance of the IORTE findings with those of the pathological examination of the tumors was assessed (The registration no. 1418). Results Among the 21 HCCs, 20 were classified as “HCC pattern” (type 3, 4, or 5), resulting in a sensitivity of 95.2%, a specificity of 66.7% and an accuracy of 81.0%. Ten out of the 16 adenocarcinomas were classified as “adenocarcinoma pattern” (type 6), resulting in a sensitivity of 62.5%, a specificity of 92.3% and an accuracy of 81.0%. Conclusion IORTE is feasible and provides useful information on the elasticity of liver tumors in LH, in which conventional tumor palpation is difficult.

Although achieving a sustained virological response (SVR) in hepatitis C virus (HCV) infection is recognized as improving liver function and reducing hepatocellular carcinoma (HCC) development, its impact on HCC recurrence is unclear. This study investigated how preoperative SVR achievement by interferon treatment affects HCC recurrence in patients undergoing hepatic resection. The study subjects were 521 patients with HCV infection who underwent initial and curative hepatic resection for HCC. To adjust for confounding factors between the SVR and non-SVR groups, propensity score-matching analysis was performed. After propensity score matching, 45 of the 49 patients in the SVR group, and an equal number of the 472 patients in the non-SVR group, were matched. The two groups had similar distributions of clinicopathological characteristics. In the matched cohort, the 3-, 5-, and 7-year recurrence-free survival rates after surgery were 56, 45, and 37%, respectively, in the SVR group, and 34, 23, and 7.2%, respectively, in the non-SVR group (p = 0.033). Additionally, the 3-, 5-, and 7-year overall survival rates after surgery were 82, 80, and 75%, respectively, in the SVR group, and 78, 64, and 44%, respectively, in the non-SVR group (p = 0.065). The 1- and 2-year cumulative recurrence rates in the early phase showed no significant difference between the SVR and non-SVR groups (p = 0.27). however, the 3-, 5-, and 7-year cumulative recurrence rates in the late phase were 14, 32, and 43%, respectively, in the SVR group, and 33, 55, and 86%, respectively, in the non-SVR group (p = 0.037). Achievement of SVR may reduce postoperative recurrence after hepatic resection.

Background & Aims Presence of hepatic vein tumor thrombosis (HVTT) in patients with hepatocellular carcinoma (HCC) is regarded as signaling an extremely poor prognosis. However, little is known about the prognostic impact of surgical treatment for HVTT. Methods Our database of surgical resection for HCC between October 1994 and December 2011 in a tertiary care Japanese hospital was retrospectively analysed. We statistically compared the patient characteristics and surgical outcomes in HCC patients with tumor thrombosis in a peripheral hepatic vein, including microscopic invasion (pHVTT), tumor thrombosis in a major hepatic vein (mHVTT), and tumor thrombosis of the inferior vena cava (IVCTT). Among 1525 hepatic resections, 153 cases of pHVTT, 21 cases of mHVTT, and 13 cases of IVCTT were identified. Results The median survival time (MST) in the pHVTT and mHVTT groups was 5.27 and 3.95years, respectively ( p =0.77), and the median time to recurrence (TTR) was 1.06 and 0.41years, respectively ( p =0.74). On the other hand, the MST and TTR in the patient group with IVCTT were 1.39years and 0.25year respectively; furthermore, the MST of Child-Pugh class B patients was significantly worse (2.39 vs. 0.44years, p =0.0001). Multivariate analyses revealed IVCTT (risk ratio [RR] 2.54, p =0.024) and R 1/2 resection (RR 2.08, p =0.017) as risk factors for the overall survival. Conclusions Hepatic resection provided acceptable outcomes in HCC patients with mHVTT or pHVTT when R0 resection was feasible. Resection of HCC may be attempted even in patients with IVCTT, in the presence of good liver function.

Background Pancreas-sparing duodenectomy (PSD) is a promising alternative procedure to pancreaticoduodenectomy for the treatment of duodenal tumors with low-grade malignant behavior. Methods Between March 2003 and September 2012, PSD was performed in 7 patients with a gastrointestinal stromal tumor (GIST) in the second (n = 5) or third (n = 2) portions of the duodenum. The short- and long-term outcomes of treatment were analyzed in all patients. Results The median blood loss was 160 mL, and the median operative time was 315 minutes. No pancreatic leakage or perioperative mortality occurred. Surgical margins were negative in all cases. All patients were alive at the median follow-up time of 42 months after PSD. The recurrence-free 5-year survival rate was 53% in all patients. Hepatic metastases developed in 2 of the 5 patients with high- or intermediate-grade risks at the time of diagnosis. Hepatic resection was performed, and imatinib mesylate was administered in the 2 cases. Conclusions Good short- and long-term outcomes and surgical curability were observed in patients treated with PSD for duodenal GIST.