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This study aimed to retrospectively analyse adverse predictors to identify patients with huge hepatocellular carcinoma who were not appropriate candidates for hepatic resection.From 551 patients with hepatocellular carcinoma who underwent hepatectomy between 1992 and 2019, 92 were diagnosed with huge hepatocellular carcinoma (diameter10 cm) and 115 were diagnosed with large hepatocellular carcinoma (diameter=5-10 cm). Clinical features and overall and disease-free survival rates were compared between the two groups.Cumulative overall survival was significantly worse in the huge group than in the large group (p=0.035). In the huge group, multivariate analyses revealed that liver cirrhosis, multiple intrahepatic metastases (≥4), poor histological grade, and macroscopic portal vein invasion were significantly associated with poor prognosis.We identified four adverse predictors of survival and determined that patients with two or more predictors are not appropriate candidates for straightforward hepatic resection.

Background Cirrhosis-associated portal vein thrombosis (CA-PVT) has been reportedly observed in 5–30% of cirrhotic patients. Moreover, the acute exacerbation of CA-PVT is likely to occur after certain situations, such as a status after abdominal surgery. Safety and efficacy of the direct-acting oral anticoagulant (DOAC) used for cirrhotic patients have been being confirmed. However, use of the DOAC as an initial treatment for CA-PVT appears still challenging especially in the early postoperative period after major surgery in terms of unestablished efficacy and safety in such occasion. Case presentation We herein report a case of the acute exacerbation of CA-PVT in the early postoperative period after abdominal surgery, which was successfully treated with DOAC, edoxaban used as an initial treatment. The patient was a 79-year-old Japanese male with alcoholic cirrhosis. The patient suffered choledocholithiasis and had a mural chronic CA-PVT extending from the superior mesenteric vein to the portal trunk. He underwent open cholecystectomy and choledochotomy. Early postoperative clinical course was uneventful except for abdominal distension due to ascites diagnosed on postoperative day (POD)7 when hospital discharge was planned. Contrast enhancement computed tomography (CE-CT) taken on POD 7 revealed the exacerbation of the CA-PVT. Despite recommendation for extension of hospital admission with low molecular weight heparin treatment, the patient strongly hoped to be discharged. Unwillingly, we selected DOAC, edoxaban, as an initial treatment, which was commenced the day after discharge (POD8). As a result, the remarkable improvement of the exacerbated CA-PVT was confirmed by the CE-CT taken on POD21. Any bleeding complications were not observed. Although a slight residue of the CA-PVT remains, the patient is currently doing well 4 years after surgery and is still receiving edoxaban. Any adverse effects of edoxaban have not been observed for 4 years. Conclusions A case of successful treatment of the acute exacerbation of CA-PVT with edoxaban was reported. Moreover, edoxaban has been safely administered in a cirrhotic patient for 4 years. The findings obtained from the present case suggest that DOAC can be used as an initial treatment for CA-PVT even in early postoperative period after major abdominal surgery.

Background and Objectives Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established. Methods Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature. Results A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs. Conclusion The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores. publishedVersion

Purpose This study aimed to investigate gender-dependent antitumor immune response to neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC) patients. Methods This study enrolled 58 patients (25 females and 33 males) with borderline resectable PDAC who underwent R0 surgical resection after NACRT. The resected tumor specimens were analyzed for tumor-associated macrophages (TAMs); tumor-infiltrating lymphocytes (CD8+ and CD4+ T cells); regulatory T cells; and IRF-5-expressing cells using immunohistochemical staining for CD163, CD204, CD8, CD4, Foxp3, and IRF-5 antigen. The relationship between clinicopathological features and clinical outcomes was evaluated using multivariate Cox proportional hazard analysis. Results Females had longer overall survival (P = .044) and relapse-free survival (P = .044) than males. The CD204+ TAM number was significantly lower in females than in males (P = .009). No significant difference occurred between female and male patients in other tumor-infiltrating immune cells. IRF-5+ cell number was significantly higher in female patients (P = .002). Negative correlation occurred between CD204+ cells and IRF-5-positive cells (P = .003, r = -.385). Conclusions Female gender was an independent prognostic factor possibly due to the greater reduction in CD204+ TAM infiltration in tumors after NACRT. The beneficial effects of NACRT on TAMs' infiltration might be associated with gender-dependent IRF-5 expression.

Background/ Aim: Currently, there is no classification system specializing in recurrent inguinal hernia (RIH) after open-surgery. For this reason, in this study we proposed one so as to understand the causes of RIH. Patients and Methods: Recurrence of IH after suture-repair was classified either as the tissue-loosening (TL) or the tissue-disruption (TD) type. Recurrence after open-mesh-repair was classified according to the locational relation between the hernia-defect and the mesh, as follows: i) mesh-distant (MD), ii) para-mesh (PM), iii) mesh-migration (MM), and iv) unclassifiable (UC). Fifty-two RIHs in 48 patients were classified, using this system, and analyzed. Results: This system-based classification led to the identification of: i) MM in 11 lesions, ii) PM in 11, iii) MD in 10, iv) TL in 7, v) TD in 5, and vi) UC in 8 lesions. The median time to recurrence (MTR) was significantly shorter in patients who had previously undergone a mesh-repair (n=34) compared to those who had undergone a suture-repair (n=13) [Mesh-repair vs. suture-repair MTR: 1.6 years (0.1-20) vs. 30 years (15-72), p

IMPORTANCE: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon’s direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. OBJECTIVE: To determine the optimal margin width in CRLM by using artificial intelligence–based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics. DESIGN, SETTING, AND PARTICIPANTS: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité–University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021. EXPOSURES: Hepatectomy. MAIN OUTCOMES AND MEASURES: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence–based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory–based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values. RESULTS: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort. CONCLUSIONS AND RELEVANCE: This cohort study used artificial intelligence–based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

A duct-to-duct-biliary-anastomosis is the preferred biliary reconstruction technique in liver transplantation; biliary complications remain the major concerns for the technique. We examined the significance of the intramural vascular network of the extrahepatic bile duct (EBD) and its relevant vessels. We microscopically examined the axial sections of the EBD with 5 mm intervals of 10 formalin-fixed deceased livers. The luminal-areas of the 3 and 9 o'clock arteries correlated significantly and positively with the distance from the bifurcation of the right and left hepatic ducts (the 3 o'clock artery

A 63-year-old man showed massive ascites, massive pleural effusion, severe lower-extremity edema, and repeated esophageal variceal bleeding. Two-year previously, he received 13-courses of oxaliplatin-based chemotherapy (OBC) followed by associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for multiple colorectal cancer liver metastases but developed a solitary remaining liver metastasis and multiple lung metastases 2 months after the ALPPS, for which multiple regimens of chemotherapy were conducted. The symptoms were considered attributable to the OBC-associated portal-hypertension. Water-retention symptoms were mitigated by the use of tolvaptan but the variceal bleeding necessitated frequent endoscopic treatments and disallowed restarting antineoplastic treatment. Transjugular intrahepatic portosystemic shunt (TIPS) was considered undesirable because TIPS in this patient might have prohibited future repeat hepatectomy. Thus, the patient underwent splenectomy and surgical portosystemic shunting. Since then, the portal-hypertension symptoms were completely resolved. Thereafter, chemotherapy was able to be recommenced. Moreover, repeat hepatectomy was performed. A literature review demonstrated that radiological and/or surgical interventions for the OBC-associated portal-hypertension have been reported in 31 cases to date. However, this report is the first to show a case of successful treatment of the OBC-associated portal-hypertension with splenectomy and surgical portosystemic shunting, which allowed subsequent chemotherapy followed by repeat hepatectomy.

Surgeons tend to avoid performing completely laparoscopic repair (CLR) for recurrent inguinal hernia (RIH) that developed after the open posterior mesh repair (OPMR). For many, totally extraperitoneal repair or transabdominal preperitoneal repair after OPMR seems difficult because the previously placed mesh may pose an obstacle during the exfoliation of the parietal peritoneum. Moreover, these procedures could cause chronic pain if the “trapezoid of disaster” is injured. In this small case series, we describe our operative technique for CLR for RIH after OPMR, including modified transabdominal preperitoneal repair and modified intraperitoneal onlay mesh repair. The short‐term and midterm outcomes of this procedure are also reported. Although we recognize the need for further analysis involving many more cases and a longer follow‐up period, we will continue to perform CLR for RIH after OPMR because the results of this small case series were favorable.

Background/purpose Early drain removal (EDR) based on drain fluid amylase level (DFA) after pancreaticoduodenectomy excluded 15%-40% patients from EDR because of inappropriate DFA. Methods Of 198 pancreatoduodenectomy cases, we used the first 105 cases as an exploration cohort to construct the optimal criteria for EDR on postoperative day (POD)4 that were applied to the subsequent 93 cases used as the validation cohort. After that, we examined another 142 patients to further assess the efficacy of the new EDR criteria. Results Of the four independent predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) ([1] soft pancreas, [2] positive drain fluid culture on POD1, and [3] serum C-reactive protein [CRP] ≥13 mg/dL on POD4) in the exploration cohort, EDR was applied to cases in the validation cohort meeting the [2] and/or [3], enabling 96% (89/93) applicability of EDR. Outcomes were improved in the validation cohort compared to the exploration cohort; CR-POPF: 8.6% vs 25.7%, P = .005; Dindo-Clavien grade ≥ 3 complications: 23.7% vs 41.9%, P = .007; and median hospital stay (day): 21 vs 27, P = .005. The subsequent 142 patients showed 92% (131/142) applicability of EDR and 5.6% (8/142) incidence of CR-POPF. Conclusions Our new criteria for EDR, without DFA, enabled ≥ 90% applicability of EDR and reduced CR-POPF.

Backgrounds The term "elderly" seems to have been used as "vulnerable to various stresses" but not well defined. To define the "elderly", we investigated whether the increased age causes unfavorable changes in several immunoinflammatory indices that indicate the increased vulnerability in the surgical field. Patients and methods One-hundred forty-two patients undergoing an elective-uncomplicated laparoscopic cholecystectomy (within 60 min and without intraoperative-cholangiography, bile spillage, or open conversion) were retrospectively investigated. Before surgery, immediately after surgery, and on postoperative day (POD)1, whether the patient age correlated the following variables was examined: neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-C-reactive-protein ratio (LCR), C-reactive-protein-to-albumin ratio (CAR), and others. Results The immunoinflammatory indices most unfavorably changed on POD1. The age correlated neither lymphocyte-to-monocyte ratio nor platelet-to-lymphocyte ratio on POD1, when NLR, LCR, and CAR showed the significant correlation with the age. Multiple regression analyses determined the following variables as the independent determinants of these 3 indices on POD1: age, intraoperative minimum body temperature ≥35.5°C (IntMinBT ≥35.5°C), maximum heart rate during POD0-1 (MaxHR) for NLR; age and IntMinBT ≥ 35.5°C for LCR; and age and MaxHR for CAR. The threshold of "elderly" was determined as 102-year-old for NLR, 94-year-old for LCR, and 97-year-old for CAR. Conclusions The increased age causes the unfavorable changes in early postoperative immunoinflammatory indices after the uncomplicated laparoscopic cholecystectomy. Thus, the term "elderly" can be rephrased by the term "vulnerable to various surgical stresses." The thresholds for "elderly" defined herein seem impractical. Namely, the increased vulnerability caused by the aging seems modified by the individual surgical procedures.

Background We sought a diagnostic tool using perioperative variables that might predict post-hepatectomy liver failure (PHLF). Patients and methods In 68 patients undergoing major hepatectomy, data on inflammatory markers and coagulation factors were prospectively collected and were compared between patients with International Study Group of Liver Surgery definition grade B/C PHLF (LF group) and those without LF (non-LF group). Results Preoperatively, the LF group (n=9; 13.2%) had a lower platelet count and a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity and a higher prothrombin time-International Normalized Ratio (PT-INR) than the non-LF group. On postoperative day 1, the LF group had significantly higher serum interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), and IL10 levels than the non-LF group. The logistic regression model that included preoperative PT-INR and CCL2 on postoperative day 1 predicted grade B/C PHLF with 100% sensitivity and 89.8% specificity. Conclusion Our findings suggest that the combination of preoperative PT-INR and CCL2 on postoperative day 1 can predict PHLF earlier and precisely after major hepatectomy.

Background The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. Methods From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. Results A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy. Conclusions While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.

To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.

Introduction The World Health Organization (WHO) proposed an integrated classification for intraductal papillary neoplasm of the bile duct (IPNB) in 2010. However, IPNB reportedly shows considerable geographic variation. This Japanese single-institution study examined outcomes of surgery for IPNB and the prognostic impact of immunohistochemical mucin expression patterns. Materials and methods Patients with IPNB were identified from 413 patients who underwent curative-intent surgery for biliary tract (excluding gallbladder) neoplasms from 1992 to 2016 by retrospective macro- and microscopic reevaluation of resected specimens. Their clinicopathological variables were analyzed. Results Twenty-two (5%) 2010 WHO classification-based patients with IPNB were identified. The other 391 patients had common-type cholangiocarcinoma. The histopathological grade was low/intermediate in 2 patients (9%), high in 8 (36%), and invasive carcinoma (ICa) in 12 (55%). The 10-year overall survival rate was 100% in 10 patients with low–high grade IPNB and 69% in 12 patients with ICa. These rates were significantly (p = 0.018) or marginally (p = 0.089) better than that (38%) of 391 other-cholangiocarcinoma patients. In the 12 patients with ICa, R0 or R1 resection, MUC5AC, and MUC6 expression significantly affected survival. Notably, all seven patients with ICa exhibiting MUC5AC expression survived throughout the study period, while four of five patients with ICa who did not exhibit MUC5AC expression died of recurrence (with vs. without MUC5AC: 10-year overall survival, 100% vs. 60%, respectively; p = 0.018). Conclusion Our 24-year, single institution's experience suggests that Japanese patients with IPNB favorably respond to surgery, even with ICa. MUC5AC and MUC6 expression may be predictive of favorable outcomes.

Background We sought to expand the clinico-anatomical limit of the proximal ductal margin (Limit-PDM) for resectability of hilar cholangiocarcinoma (HCCA). Methods The practical boundary of the hilar plate (PBHP) was defined as the location where the bile duct (BD) could not be isolated by dissection. The distance between PBHP and two well-known clinical landmarks of Limit-PDM, the right edge of the bifurcation of the anterior and posterior branch of the right portal vein (Posterior-Landmark) and the left edge of the umbilical portion of the portal vein (Left-Landmark), and histological features around the PBHP were assessed using 55 adult cadaver livers. Results BD was almost always isolatable beyond the traditional clinical landmarks. The median distance was 6.9 mm (interquartile range [IQR] 6.0-8.3 mm) between the PBHP and the Posterior-Landmark, and 8.9 mm (IQR 6.7-10.2 mm) between the PBHP and the Left-Landmark. Histologically, the sheath surrounding the portal triad was loose, thick with few elastic fibers and small arteries near the hepatic hilum. Near the PBHP, the sheath was dense, thin, and abundant with elastic fibers and small arteries. Conclusions Limit-PDM is more peripheral than the traditional clinical landmark-based margin and histological transition near the PBHP was revealed.

Objective: To assess the safety and efficacy of “polyhedral fenestration technique” (PFT), which we newly developed, in combined hepatectomy and cyst fenestration (CHCF) for symptomatic polycystic liver disease (PLD). Summary of background data: CHCF for PLD has been reportedly less efficacious for its invasiveness because 50% to 70% patients suffered recurrent symptoms after CHCF. Methods: Patient characteristics, intra- and early postoperative variables were compared between 5 PLD patients undergoing CHCF performed with PFT (PLD group) and 95 patients with diseases other than PLD receiving hepatectomy without biliary reconstruction during the same period (Control group) to assess safety of PFT. Chronological changes in total liver volume (TLV) measured by computed tomography (CT) volumetry as well as recurrent symptoms after CHCF were investigated to assess long-term outcomes. Results: Although ≧ Clavien-Dindo grade 2 complications were more common in the PLD group than in the Control group (PLD vs Control, 5/5[100%] vs 27/95[28%], p=0.004), patient characteristics, intra-, and early postoperative variables, including ≧ Clavien-Dindo grade 3 complications, were comparable among the 2 groups. Postoperative observational period of the 5 PLD patients ranged 30 to 88 months with a median of 63. CT volumetry revealed that TLV continued to reduce up to 1 year after surgery and thereafter retained less than 0.5 times of preoperative TLV in all patients. Recurrent liver enlargement or recurrent symptoms were not observed in any of the 5 PLD patients. Conclusions: Although our case series was very small, newly-developed PFT in CHCF for PLD yielded acceptable safety and excellent long-term outcomes.

Introduction Two novel clinical risk scores (CRS) that incorporate KRAS mutation status (modified CRS (mCRS) and GAME score) were developed. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS. Methods Patients undergoing hepatectomy for CRLM (2000-2018) in ten centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrel's C-index and Akaike's Information Criterion. Results In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14405, 14447, and 14319, respectively. Conclusion In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.

Introduction A vertical penetration of the thread through the abdominal wall for the hernia defect closure in laparoscopic ventral/incisional hernia repair (LVIHR) is difficult especially in the large defect cases when applying the existing techniques. Materials Sixteen LVIHRs were performed using the suture technique for defect closure we newly developed. Surgical technique With the subcutaneous switching, our technique only requires the suture‐passer and easily enables the vertical penetration of the thread through the abdominal muscular wall even in the large defect cases. Discussion The defect closure in LVIHR tends to be complicated in the large defect cases. Thus, we devised this technique for the easy, reliable, and firm closure even in the large defect cases. Although the sample size was currently very small, we consider that the favorable outcomes have been obtained through our technique because any noticeable complications, such as mesh bulging or recurrence, have not been observed currently.

The concept of “borderline resectable” was recently introduced to the field of surgery for pancreatic cancer, and surgical outcomes for this disease with extremely dismal prognosis have improved since the introduction of this concept. However, no such concept has yet been introduced to the field of surgery for hilar cholangiocarcinoma (HCca). To determine a definition and criteria for “borderline resectable” in the field of surgery for HCca. Retrospective analysis of 88 patients undergoing curative-intent surgery for HCca at our institution between May 1992 and December 2008 to clarify independent prognostic factors. Survival outcomes were obtained for these 88 patients, with a 5-year overall survival rate of 31.8%. Independent factors predictive of cancer death were determined by multivariate analysis to be the presence of regional lymph node metastasis (LNM) and pathological confirmed vascular invasion (VI). Cumulative survival rates of 23 patients with both LNM and VI who underwent surgery were significantly worse than those of the remaining 65 surgically treated patients and similar to those of 26 patients who were considered to have unresectable disease and treated with non-surgical multidisciplinary treatment during the same study period. Outcomes of surgery for cases of HCca showing regional LNM and VI were no better than those of non-surgical treatment for unresectable disease. Coexistence of these two factors indicates oncologically dismal condition and thus such cases should be considered “borderline resectable.” Treatments additional to surgery are required for “borderline resectable” cases to obtain better outcomes.

The aim of this study was to examine if the prognostic significance of margin status in hepatectomy for colorectal cancer liver metastasis (CRLM) varies for different levels of tumor burden because hepatectomy indications for CRLM have been recently expanded to include patients with a higher tumor burden in whom achieving an R0 resection is difficult. Clinicopathological variables in an exploration cohort of 290 patients receiving hepatectomy in Japan for CRLM were investigated. R0 resection was defined as a margin width > 0 mm. Tumor burden was assessed using the recently introduced Tumor Burden Score (TBS), which was calculated as TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2. The principal findings were validated using a cohort from the United States. R1 resection rates significantly increased as TBS increased: 4/86 (4.7%) in patients with TBS

Background/aim Cholangiocarcinoma and pancreatic carcinoma are major malignancies that cause obstructive jaundice (OJ). This study aimed to develop a simple and easily reproducible rat model of reversible OJ (ROJ). Materials and methods OJ was induced by clamping the common bile duct (CBD) using a U-shaped titanium hemoclip and its base was attached by ligation using 2-cm long 4-0 polypropylene suture. An anti-adhesive sheet was placed around the CBD. OJ was mitigated by pulling the suture to remove the clip under laparotomy 3 days later. Serum chemistry and liver histopathology were compared between the ROJ group and sham surgery (SH) groups. Results Three days after inducing OJ, serum total bilirubin, aspartate aminotransferase, and alanine aminotransferase were remarkably elevated in the ROJ group and thereafter reduced significantly after mitigating OJ. Similar findings were confirmed by histopathology. Conclusion Our rat model of reversible OJ was considered simple and easily reproducible.

Ascites necessitating persistent drainage or paracentesis after drain removal has been found among early postoperative complications after combined hepatectomy and cyst fenestration (CHCF) for polycystic liver disease (PLD). It has been reportedly observed in 20% to 70% of cases and seemed to easily cause recurrent symptoms unless properly treated. We utilized distilled water lavage for treating localized fluid collection after combined hepatectomy and cyst fenestration for PLD. A 63-year-old female patient underwent CHCF for PLD, which caused severe abdominal fullness. Early postoperative course was uneventful until 10 days after surgery when the patient suffered sudden abdominal fullness and resultant severe anorexia because of right subphrenic massive localized monolocular fluid collection diagnosed by abdominal computed tomography—although total liver volume was reduced to less than half of that before surgery. Percutaneous drainage relieved symptoms immediately, but the drainage tube could not be removed because of massive outflow. Then we utilized distilled water lavage for treating this condition. After that, drain outflow dramatically reduced and the drainage tube was successfully removed. Total liver volume of the patient continued to reduce up to 1 year after surgery and retained less than one-third of preoperative total liver volume thereafter. Sustained reduction of total liver volume in the present case suggested a sclerosant effect of hypotonic cytocidal property of distilled water for cyst endothelium and/or retrieved effectiveness of fenestration. Hence, we consider this approach to be useful for patients with PLD receiving CHCF and thus present it here.

We describe a case of bowel strangulation caused by massive peritoneal adhesion as a result of effective chemotherapy. A 71-year-old man, who had obstructive descending colon cancer with massive peritoneal metastases and, therefore, received palliative surgery consisting of diverting colostomy and sampling of peritoneal nodules, developed bowel strangulation on day 4 of the 2nd course of chemotherapy, including irinotecan, l-leucovorin, and 5-fluorouracil. Emergent celiotomy showed a massive intraperitoneal adhesion formed around several intestinal loops, which were not observed at the prior surgery. One loop was strangled, but recovered by adhesiotomy alone. Intestinal loops were formed around aggregates of peritoneal nodules as the centers, several of which were then sampled. We closed the abdomen after all intestinal loops were eradicated by total enterolysis. Fortunately, the patient has been doing well and received chemotherapy without recurrent bowel obstruction 10 months after the present episode. Histological findings of the aggregates causing intestinal loops demonstrated extensive necrosis of cancerous tissue surrounded by fibrosis with abundant lymphocyte infiltration. These findings were not observed in the specimen sampled before chemotherapy, suggesting that intestinal loops were caused by inflammatory adhesion occurring around the peritoneal metastases as a result of effectiveness of chemotherapy.

NCCN and Japanese clinical guidelines for the treatment of biliary tract cancer (BTC) addressed gemcitabine–cisplatin combination (GC) as first-line chemotherapy for patients with advanced BTC ineligible for surgery in 2013. However, gemcitabine–S1 combination therapy (GS) has been widely used as first-line treatment in Japan because Japanese social insurance coverage of S-1 for BTC was approved prior to that of cisplatin. To elucidate the efficacy and tolerability of GC as second-line chemotherapy for patients with unresectable BTC after failure of GS. Between September 2008 and August 2011, patients with unresectable BTC who provided informed consent and received GC comprising gemcitabine at 1000 mg/m2 and cisplatin at 20 mg/m2 given on days 1 and 8 in a 3-week cycle after failure of GS were included in the present study. Clinical data from these patients were collected prospectively. Primary endpoints were overall survival and time to progression (TTP). Secondary endpoints were response and tolerability. Twenty-seven patients were analyzed. Median survival time (MST) and TTP from the beginning of second-line treatment were 6.5 and 3.3 months, respectively, whereas MST from the commencement of first-line therapy was 12.06 months. One patient showed partial response, 16 had stable disease and 10 experienced disease progression. As a result, disease control rate was 63.0%. In total, 119 courses (median, 4; range, 1–15) were administered. Discontinuation of GC due to drug toxicities was not observed. Although some issues remain to be clarified, mainly due to the small sample size, this single-institution experience with GC as second-line treatment after failure of GS showed acceptable outcomes and good tolerability.

Background International Study Group of Liver Surgery (ISGLS) proposed the standardized definition for bile leakage (BL) after hepatectomy (Hx) at 2011 to precisely perceive incidence and predictive factors of this critical condition. Methods We conducted a multicenter retrospective study using the ISGLS definition of BL after Hx. Results Perioperative data regarding 631 patients undergoing elective Hx for hepatic tumors without biliary reconstruction performed between January 2009 and December 2011 were analyzed. BL was observed in 30 patients (4.8%). (Grade A, 8(1.3%); B, 21(3.3%); C, 1(0.2%)). Five independent predictors (diagnosis of liver metastases, prolonged operation, high risk procedures defined as Hx with broad exposure of the hilar Glissonean sheath, low platelet count and high serum total bilirubin on postoperative day 1) for grade B/C BL were elucidated by the multivariate analysis. When the study cohorts were divided into groups by number of accompanying these predictors, the more the accompanying independent predictors, the higher the incidence of BL. Notably, incidence of BL exceeded 40% in patients with 4 or more these predictors. Conclusions Risk stratification for BL after Hx can be achievable using independent predictors clarified in this study. However, proper management for high risk patients remains to be elucidated.

A 64-year-old woman was diagnosed with advanced gastric cancer with solitary liver metastasis. Although the HER2 status of the tumor was IHC2+, no further examination for HER2 status using FISH was performed. Four courses of S-1 and cisplatin chemotherapy were administered. The primary lesion and metastatic lesion were confirmed to have partially regressed. After 4 courses of chemotherapy, an open total gastrectomy, D2 dissection, pancreatosplenectomy, and posterior segmental hepatectomy were performed. Her postoperative course was uneventful. On histopathology, cancer cells were found in the resected stomach and resected liver. However, the HER2 statuses of the resected specimens were negative. After discharge, she received S-1 therapy for 1 year. Upon evaluation 1 year and 1 month postoperatively, the tumor marker CA19-9 was elevated. An enhanced CT scan showed multiple lung metastases and lymph node metastases in the pancreatic tail. Three courses of XELOX therapy(capecitabine and oxaliplatin)were administered. However, tumor marker levels continued to increase, and the metastasis continued to enlarge. Although the HER2 status of the resected site was negative, the HER2 status of the biopsy specimen before chemotherapy was positive on FISH. Therefore, weekly paclitaxel and trastuzumab therapy was initiated and repeated for 6 courses, after which an enhanced CT showed significant reduction(nearly CR)of multiple lung metastases and lymph node metastases. This suggests that HER2-negative conversion had occurred at the resected site. However, the HER2 status of the metastatic sites was considered positive.

The aim of this study was to assess the efficacy of combined resection and reconstruction (CRR) of the hepatic artery (HA) in surgery for hilar cholangiocarcinoma (HC). Among 172 patients who underwent surgical resection for HC, the following three groups were defined according to the type of vascular reconstruction: VR(−) group, in which neither CRR of the portal vein (PV) nor HA was performed (n = 74); VR-PV group, in which only CRR of the PV was required (n = 54); and VR-A group, in which CRR of the HA was performed either with or without CRR of the PV (n = 44). Clinicopathological variables and clinical outcomes were compared among the three groups. Although the VR-A group showed significantly more advanced disease than other groups, the R0 resection rate was comparable among the three groups (VR(−), 74 %; VR-PV, 80 %; VR-A, 80 %). The 5-year disease-specific survival rate was also comparable among the three groups (VR(−), 45.6 %; VR-PV, 51.2 %; VR-A, 22.3 %), but tended to be worse in the VR-A group than in the other groups. A similar trend was observed in morbidity rate. Lymph node metastasis was more frequent in the VR-A group (59 %) than in the other groups (VR(−), 33.8 %; VR-PV, 50 %). In the VR-A group, lymph node metastasis (p = 0.004) and adjuvant chemotherapy (p = 0.006) were determined to represent independent prognostic factors for survival according to multivariate analysis. CRR of the HA was considered efficacious in selected patients; however, long-term outcomes of the VR-A group seem unsatisfactory. Treatments additional to surgery may be necessary in cases requiring CRR of the HA.

Background We developed 90%-hepatectomized mice that were the fatal model, and analyzed the gene expression profiles using a complementary DNA (cDNA) microarray to clarify the mechanisms of hepatic failure after excessive hepatectomy. Materials and Methods Ribonucleic acid (RNA)s from the remnant hepatic tissue of 70%- and 90%-hepatectomized mice were labeled with fluorescent dyes, and hybridized to the Riken set of 39,168 full-length enriched mouse cDNA arrays. The gene expression profiles in 90%- and 70%-hepatectomized mice were analyzed by scanning date for fluorescent dye signals. Results The down-regulated genes in 90%-hepatectomized mice were genes activating extracellular matrix (ECM) remodeling (matrix metalloproteinases, laminins, and integrins), genes related to cytokines (tumor necrosis factorα converting enzyme, and Janus kinase 3) that were related to the priming, genes related to growth factor (heparin-binding epidermal growth factor-like growth factor and others), and genes promoting cell cycle progression (cyclin D1, D2, and E2) that were related to the progression of hepatocytes. The up-regulated genes were genes inhibiting ECM remodeling [plasminogen activator inhibitors (PAIs)]. Conclusions Hepatic failure after hepatectomy was characterized by the inhibition of hepatic cell cycle priming and progression both induced by ECM remodeling in liver regeneration. Particularly, the overexpression of PAIs was thought to play the major role in the first step of inhibition of ECM remodeling.

Background/Aim Prostaglandin E 1 (PGE 1 ) has a wide-ranging effect on cytoprotection. Overproduction of heat shock protein 70 (HSP70) in the liver protects hepatocytes under various pathologic conditions. In this study, we examined the effect of a nontoxic HSP-inducer, PGE 1 , on acute liver failure after 95% hepatectomy in rats. Methods PGE 1 or vehicle was intravenously administered to rats 30 min before and during hepatectomy. Results Nine of 30 rats pretreated with PGE 1 survived, whereas all 20 rats pretreated with vehicle died within 96 h after operation. During the 24-h postoperative period, PGE 1 significantly suppressed the release of alanine aminotransferase and elevation of hyaluronic acid. Histological examination showed that the vacuolized hepatocytes and round hepatocytes with pyknotic nuclei are frequently seen in rats pretreated with vehicle, whereas active regeneration is seen in rats pretreated with PGE 1 . During the first 24 h after surgery, HSP70 induction was absent in the residual livers of vehicle-treated rats. In contrast, PGE 1 stimulated the HSP accumulation within 24 h, and viable hepatocytes contained abundant HSP70 in their nuclei. Conclusion Our results suggest that PGE 1 may prevent acute liver failure after massive hepatectomy, at least in part, by enhancing HSP70 production in the residual liver.

Background/Aims: Nitric oxide synthase 2 (NOS2) is expressed during liver regeneration after a partial hepatectomy (PHx); NOS2 subsequently synthesizes nitric oxide (NO). However, the role of NOS2-synthesized NO in post-PHx liver regeneration remains unclear. We investigated the role of NOS2-synthesized NO in liver regeneration. Methods: NOS2 knockout (NOS2-KO) mice and control mice were subjected to PHx. Liver mass recovery and serum alanine aminotransferase (ALT) levels were then evaluated. The expressions of Ki-67 and single-strand DNA were also evaluated in remnant liver specimens. Differences in the gene expression profiles of the two groups of remnant liver specimens were analysed using a microarray and were validated using a reverse transcription-polymerase chain reaction (RT-PCR). Results: In NOS2-KO mice, liver regeneration was delayed and apoptosis and serum ALT levels were higher than the levels in the control mice. A microarray study and RT-PCR revealed that heat shock protein 70 family (HSP70 family), haeme oxygenase 1 (Hmox1), neuropilin 1 (Nrp1) and epidermal growth factor receptor (EGFR) were downregulated in NOS2-KO mice. Conclusions: NOS2-synthesized NO may improve hepatocyte viability through the induction of the HSP70 family and Hmox1 and may sensitize the remnant liver to growth factors through the induction of Nrp1 and EGFR post-PHx.