Objective Definition and Optimized Strategy for "Biologically Borderline Resectable" Colorectal Liver Metastases.

BACKGROUND: The prognostic benefit of preoperative chemotherapy leading to conversion surgery for unresectable colorectal liver metastases (CRLM) is well recognized, while that of neoadjuvant chemotherapy (NAC) compared with upfront surgery (UFS) for resectable CRLM is negligible. This study aims to assess the prognostic benefit and search for optimal indication of NAC for resectable advanced CRLM by establishing an objective definition of biologically borderline resectable (bBR) CRLM. METHODS: A bicentric retrospective analysis of patients with CRLM undergoing curative-intent initial liver resection between 2007 and 2021 was performed. An original classification matrix was established, which reassessed technical resectability using virtual hepatectomy and oncological favorability using Beppu's nomogram. Patients with technically resectable but biologically unfavorable CRLM were classified into the bBR group. The propensity score matching analysis using preoperatively available factors was performed to assess long-term outcomes of the bBR-UFS and bBR-NAC groups. RESULTS: Of 831 patients reviewed, 240 were categorized into the bBR group: bBR -UFS (n = 139) and bBR-NAC (n = 101). Ten (10%) in the bBR-NAC group (n = 101) experienced biological status change from unfavorable to favorable after NAC (Biological Conversion) and showed significantly longer overall survival (hazard ratio 5.63, 95% confidence interval 1.37-23.1; P = 0.016) than the bBR-UFS group. However, after propensity score matching, no significant difference between the UFS and NAC groups (n = 67 for each) was found in long-term outcomes. CONCLUSIONS: NAC for bBR-CRLM did not enhance the prognostic impact of the following liver resection, except for a limited number of optimal candidates experiencing the Biological Conversion.

Reevaluation of Makuuchi's criteria for resecting hepatocellular carcinoma: A Japanese nationwide survey.

AIM: Although Makuuchi's criteria are widely used to determine the cut-off for safe liver resection, there have been few reports of concrete data supporting their validity. Here, we verified the utility of Makuuchi's criteria by comparing the operative mortality rates associated with liver resection between hepatocellular carcinoma (HCC) patients meeting or exceeding the criteria. METHODS: A database was built using data from 15 597 patients treated between 2000 and 2007 for whom values for all three variables included in Makuuchi's criteria for liver resection (clinical ascites, serum bilirubin, and indocyanine green clearance) were available. The patients were divided into those fulfilling (n = 12 175) or exceeding (n = 3422) the criteria. The postoperative mortality (death for any reason within 30 days) and long-term survival were compared between the two groups. RESULTS: The operative mortality rate was significantly lower in patients meeting the criteria than in those exceeding the criteria (1.07% vs. 2.01%, respectively; p < 0.001). On multivariate analysis, exceeded the criteria was significantly associated with the risk for operative mortality (relative risk 2.08; 95% confidence interval (CI), 1.23-3.52; p = 0.007). Surgical indication meeting or exceeding the criteria was an independent factor for overall survival (hazard ratio 1.27; 95% CI, 1.18-1.36; p < 0.001). CONCLUSION: Makuuchi's criteria are suitable for determining the indication for resection of HCC due to the reduction in risk of operative mortality.

Surgery versus Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Randomized Controlled Trial (SURF Trial).

Introduction: It remains unclear which surgery or radiofrequency ablation (RFA) is the more effective treatment for small hepatocellular carcinoma (HCC). We aimed to compare survival between patients undergoing surgery (surgery group) and patients undergoing RFA (RFA group). Methods: We conducted a randomized controlled trial involving 49 institutions in Japan. Patients with Child-Pugh scores ≤7, largest HCC diameter ≤3 cm, and ≤3 HCC nodules were considered eligible. The co-primary endpoints were recurrence-free survival (RFS) and overall survival (OS). The current study reports the final result of RFS, and the follow-up of OS is still ongoing. Results: During 2009-2015, 308 patients were registered. After excluding ineligible patients, the surgery and RFA groups included 150 and 151 patients, respectively. Baseline factors did not differ significantly between the groups. In both groups, 90% of patients had solitary HCC. The median largest HCC diameter was 1.8 cm (interquartile range [IQR], 1.5-2.2 cm) in the surgery group and 1.8 cm (IQR, 1.5-2.3 cm) in the RFA group. The median procedure duration (274 vs. 40 min, p < 0.01) and the median duration of hospital stay (17 days vs. 10 days, p < 0.01) were longer in the surgery group than in the RFA group. RFS did not differ significantly between the groups as the median RFS was 3.5 (95% confidence interval [CI], 2.6-5.1) years in the surgery group and 3.0 (95% CI, 2.4-5.6) years in the RFA group (hazard ratio, 0.92; 95% CI, 0.67-1.25; p = 0.58). Discussion/Conclusion: Our study did not show which surgery or RFA is the better treatment option for small HCC.

Phase I/II study of streptozocin monotherapy in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: This phase I/II study was conducted to evaluate the efficacy, safety and pharmacokinetics of streptozocin (STZ) in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors. METHODS: Twenty-two patients received up to 4 cycles of intravenous STZ at either 500 mg/m2 once daily for 5 consecutive days every 6 weeks (daily regimen) or at 1000-1500 mg/m2 once weekly for 6 weeks (weekly regimen). Tumor response was evaluated using the modified RECIST criteria ver. 1.1, and adverse events were assessed by grade according to the National Cancer Institute CTCAE (ver. 4.0). RESULTS: Fourteen (63.6%) patients completed the study protocol. No patients had complete response; partial response in 2 (9.1%), stable disease in 17 (77.3%), non-complete response/non-progressive disease in 2 (9.1%) and only 1 (4.5%) had non-evaluable disease. Excluding the latter, the response rate in the daily and weekly regimens was 6.7% (1/15) and 16.7% (1/6), respectively, with an overall response rate of 9.5% (2/21). However, the best overall response in each patient showed that the disease control rate was 100%.Adverse events occurred in all 22 patients, including 17 grade 3 adverse events in 11 patients; however, no grade 4 or 5 adverse events were reported. Prophylactic hydration and antiemetic treatment reduced the severity and incidence of nephrotoxicity, nausea and vomiting. Plasma STZ concentrations decreased rapidly after termination of infusion, with a half-life of 32-40 min. Neither repeated administration nor dose increases affected pharmacokinetic parameters. CONCLUSIONS: STZ may be a useful option for Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.

Evolutions in the Management of Hepatocellular Carcinoma over Last 4 Decades: An Analysis from the 100 Most Influential Articles in the Field.

INTRODUCTION: Over the past 4 decades, the management of hepatocellular carcinoma (HCC) has changed dramatically. The publications that have had the most significant impact on HCC management have not been quantitatively analyzed. In this article, we analyzed the 100 most influential articles over the past 4 decades using bibliometric citation analysis to characterize the evolution in HCC treatment. METHODS: The top-cited publications were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database. RESULTS: The 100 most cited articles were identified with an average of 738 citations (range: 349-6,799). There was an increase in the number of influential articles in the late 1990s, which was paralleled by an increase in reports focused on locoregional treatment of HCC. Most top 100 articles came from the USA (n = 35), followed by Italy (n = 28), mainland China (n = 26), and Japan (n = 24). The surgical management was the most studied topic (n = 33). The Annals of Surgery published the highest number of papers (n = 26) with 13,978 citations. While other 3 topics (surgical management, locoregional treatment, and outcome prediction) declined among publications beginning in the 2000s, there was an emergence of highly cited papers on targeted drugs and immune checkpoint inhibitors with a concomitant increase in the number of publications on systemic therapy. CONCLUSIONS: Based on bibliometric analysis of the literature over the last 40 years, a comprehensive analysis of the most historically significant HCC management articles highlighted the key contributions made to the evolution and advancement of this specialist field. The data should provide clinicians and researchers insight into future directions relative to the advancement of HCC management.

Adjuvant chemotherapy can prolong recurrence-free survival but did not influence the type of recurrence or subsequent treatment in patients with colorectal liver metastases.

BACKGROUND: Although liver resection is the only potentially curative treatment for colorectal liver metastases, recurrence is frequent. We previously published the early results of a randomized controlled phase 3 trial showing that adjuvant therapy with uracil-tegafur and leucovorin significantly prolongs recurrence-free survival. This study sought to elucidate the impact of adjuvant chemotherapy on patient survival after an additional follow-up period, building upon the results of our previous study. METHODS: After resection for colorectal liver metastases, patients were randomly assigned in a 1:1 ratio to receive adjuvant uracil-tegafur and leucovorin or surgery alone. Patients assigned to the uracil-tegafur and leucovorin group received 5 cycles of uracil-tegafur and leucovorin within 8 weeks after surgery. RESULTS: Patients were assigned to an adjuvant uracil-tegafur and leucovorin (n = 90) or a surgery alone (n = 90) group; 3 patients were excluded because of protocol violations. After a median follow-up period of 7.36 years (95% confidence interval, 6.93-7.87), 60 (68.2%) patients in the uracil-tegafur and leucovorin group and 61 (68.5%) patients in the surgery alone group developed recurrences. The median recurrence-free survival was 1.45 years (95% confidence interval, 0.96-2.16) in the uracil-tegafur and leucovorin group and 0.70 years (95% confidence interval, 0.44-1.07) in the surgery alone group. The locations and treatments of the first recurrences did not differ between the groups, nor did the overall survival (hazard ratio, 0.86; 95% confidence interval, 0.54-1.38; P = .54). The overall survival was significantly longer in patients who underwent curative repeated resection than in patients who received non-surgical treatment (hazard ratio, 0.25; 95% confidence interval, 0.15-0.40; P < .0001). CONCLUSION: Adjuvant uracil-tegafur and leucovorin significantly prolonged the recurrence-free survival but not the overall survival. The repeated resection was the most important factor influencing overall survival.

Is portal vein embolization safe and effective for patients with impaired liver function?

BACKGROUND AND OBJECTIVES: Portal vein embolization (PVE) is a safe and effective procedure used to increase the safety of extensive hepatectomy for selected patients. However, it is unknown whether PVE is safe for patients with impaired liver functional reserve. METHODS: Patients who underwent PVE from April 2007 to September 2016 in our hospital were retrospectively assessed. According to indocyanine green retention rate at 15 min (ICG-R15), we divided patients into Group A (≤10%), Group B (10%-20%), and Group C (>20%). We described and compared the treatment course and the outcome among the three groups. RESULTS: A total of 106 patients were assessed and divided into groups A (n = 46), B (n = 49), and C (n = 11). The morbidity and mortality after PVE showed no significant differences among the three groups (A:B:C = 37%:53%:64%, p = .16; A:B:C = 0%:0%:0%, p = 1.00, respectively). The morbidity and mortality after successive hepatectomy also showed no significant differences among the three groups (A:B:C = 55%:71%:78%, p = .19; A:B:C = 0%:2%:0%, p = 1.00, respectively). CONCLUSION: A patient with impaired liver functional reserve (ICG-R15 > 20%) can be a candidate for PVE and successive hepatectomy, as safely as a patient with normal and slightly impaired liver functional reserve (ICG-R15 ≤ 20%).

Algorithm for Resecting Hepatocellular Carcinoma in the Caudate Lobe.

OBJECTIVE: To propose an algorithm for resecting hepatocellular carcinoma (HCC) in the caudate lobe. BACKGROUND: Owing to a deep location, resection of HCC originating in the caudate lobe is challenging, but a plausible guideline enabling safe, curable resection remains unknown. METHODS: We developed an algorithm based on sublocation or size of the tumor and liver function to guide the optimal procedure for resecting HCC in the caudate lobe, consisting of 3 portions (Spiegel, process, and caval). Partial resection was prioritized to remove Spiegel or process HCC, while total resection was aimed to remove caval HCC depending on liver function. RESULTS: According to the algorithm, we performed total (n = 43) or partial (n = 158) resections of the caudate lobe for HCC in 174 of 201 patients (compliance rate, 86.6%), with a median blood loss of 400 (10-4530) mL. Postoperative morbidity (Clavien grade ≥III b) and mortality rates were 3.0% and 0%, respectively. After a median follow-up of 2.6 years (range, 0.5-14.3), the 5-year overall and recurrence-free survival rates were 57.3% and 15.3%, respectively. Total and partial resection showed no significant difference in overall survival (71.2% vs 54.0% at 5 yr; P = 0.213), but a significant factor in survival was surgical margin (58.0% vs 45.6%, P = 0.034). The major determinant for survival was vascular invasion (hazard ratio 1.7, 95% CI 1.0-3.1, P = 0.026). CONCLUSIONS: Our algorithm-oriented strategy is appropriate for the resection of HCC originating in the caudate lobe because of the acceptable surgical safety and curability.

Repeat Hepatectomy After Major Hepatectomy for Colorectal Liver Metastases.

OBJECTIVE: This study assessed predictors of survival after repeat hepatectomy and the feasibility of a repeat hepatectomy after a major hepatectomy in the patients with colorectal liver metastases (CLM). BACKGROUND: More than half of all patients who receive a curative initial hepatectomy for CLM develop hepatic recurrence, and aggressive indications for a repeat hepatectomy can improve the outcome in selected patients. However, the feasibility of repeat hepatectomy after major hepatectomy remains uncertain, and optimal selection criteria for repeat hepatectomy have not yet been established. METHODS: Data were collected retrospectively on 296 CLM patients who underwent an initial curative hepatectomy between 2007 and 2017 at our institution. The postoperative outcomes of patients undergoing a repeat hepatectomy after major hepatectomy were assessed, and independent predictors of survival were investigated. RESULTS: After a median follow-up period of 32 months, 247 patients (83%) developed disease recurrence and 122 patients (49%) underwent repeat hepatectomy. The 5-year overall survival (OS) was significantly higher in patients who underwent a repeat hepatectomy than in those who did not receive repeat hepatectomy (51% vs. 19%, respectively; P < 0.001). In a multivariate analysis, an extrahepatic lesion at the time of the repeat hepatectomy (HR, 2.49; P = 0.001) and 5 or more liver tumors at the time of recurrence (HR, 1.88; P = 0.04) remained as independent factors negatively affecting OS after repeat hepatectomy. The type of operative procedure and the intraoperative and postoperative factors at the time of the initial hepatectomy did not have any significant influence on the OS after repeat hepatectomy. No significant difference in OS was found between patients who received repeat hepatectomy after major hepatectomy (n = 43) and those after non-major hepatectomy (n = 79). CONCLUSIONS: The operative procedure and the liver tumor status at the time of the initial hepatectomy have little impact on the indications for a repeat hepatectomy for recurrent CLM. Repeat hepatectomy is feasible even if major hepatectomy was initially performed.

Precision surgery for primary liver cancer.

Liver resection remains the best curative option for primary liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. In particular, in liver resection for HCC, anatomical resection of the tumor-bearing segments is highly recommended to eradicate the intrahepatic metastases spreading through portal venous branches. Anatomical liver resection, including anatomical segmentectomy and subsegmentectomy using the dye-injection method, is technically demanding and requires experience for completion of a precise procedure. The recent development of imaging studies and new computer technologies has allowed for the preoperative design of the operative procedure, intraoperative navigation, and postoperative quality evaluation of the anatomical liver resection. Although these new technologies are related to the progress of artificial intelligence, the actual operative procedure is still performed as human-hand work. A precise anatomical liver resection still requires meticulous exposure of the boundary of hepatic venous tributaries with deep knowledge of liver anatomy and utilization of intraoperative ultrasonography.

Intratumoral Hemorrhage of Liver Metastasis from a Rectal Neuroendocrine Tumor.

A 56-year-old healthy woman was referred to our hospital for abdominal pain. Contrast-enhanced computed tomography (CT) showed a 14-cm-diameter liver tumor with intratumoral hemorrhage. We performed emergent transcatheter arterial embolization. She was referred to hepatic surgeon (M.M.) for resection. Preoperative colonoscopy showed an elevated lesion measuring 2 cm in diameter that was pathologically diagnosed as a rectal neuroendocrine tumor (NET). We performed low anterior resection of the rectum, followed by extended right hepatectomy for all hepatic lesions. Intratumoral hematoma was observed in the largest hepatic lesion (size: 150 mm×100 mm). Microscopy also indicated NET G2. We pathologically diagnosed a liver tumor from a rectal NET that bled spontaneously.

Living donor liver transplantation: looking back at my 30 years of experience.

Since I moved from the National Cancer Center to Shinshu University, I have been performing living donor liver transplantation (LDLT), which is the only way to save the life of patients with end-stage liver disease. In June 1990, we performed the first LDLT that case was the first successful case in Japan. The patient remains healthy and is enjoying a normal life still 28 years after the transplant. In 1993, we successfully performed adult-to-adult LDLT, which was the first successful case in the world. The patient enjoyed a normal life for 17 years until she died at 70 years of age. For small children, the left liver of adult donors is too large to close the abdomen. However, in adolescents or adults, even when the whole right liver is used, the volume of the graft is too small. The concept of the standard liver volume (SLV) has proven very important for this procedure and is calculated as follows: 706.2 × body surface area + 2.4. We proposed a method for evaluating the congestion of the liver by Doppler ultrasound. In addition, we devised the right lateral sector graft. Over the years, we have contributed to LDLT in many ways and published many papers. We feel that our findings are quite useful not only for LDLT but also for other hepatectomy procedures.

Practical Contribution of Virtual Hepatectomy for Colorectal Liver Metastases: a Propensity-Matched Analysis of Clinical Outcome.

BACKGROUND: Recent improvements in imaging technologies have enabled surgeons to perform precise planning using virtual hepatectomy (VH). However, the practical and clinical benefits of VH remain unclear. This study sought to assess how three-dimensional analysis using a VH contributed to preoperative planning and postoperative outcome in patients undergoing liver surgery for the treatment of colorectal liver metastases (CRLM). METHODS: From 2007 to 2017, a total of 473 CRLM patients who received curative hepatectomy were retrospectively assessed. A 1:1 matched propensity analysis was performed between patients who did not receive a VH (without 3D group: n = 188) and received a VH (3D(+) group: n = 285). RESULT: The rate of VH increased over the study period (P < 0.001). After propensity score matching (n = 150 for each group), no significant differences were observed in the intraoperative and postoperative outcome, including liver transection time, blood loss, or morbidity between the groups. More patients received a small anatomical resection (plus limited resections) in the 3D(+) group (25 vs 11%, [P = 0.03]). A submillimeter margin was less frequent in the 3D(+) group. No significant differences in the 5-year overall survival and disease-free survival rates were seen between the without 3D group and the 3D(+) group (38.0 vs. 45.9% [P = 0.99], 11.1 vs. 21.7%, respectively [P = 0.109]). CONCLUSION: Although VH did not significantly influenced on the long-term outcome after hepatectomy, a more parenchymal-sparing operative procedure (anatomical resections, plus limited resections) was selected and the risk of a submillimeter surgical margin was reduced after introduction of VH.

R1 Resection for Colorectal Liver Metastases: a Survey Questioning Surgeons about Its Incidence, Clinical Impact, and Management.

BACKGROUND: A ≥ 1-mm margin is standard for resection of colorectal liver metastases (CLM). However, R1 resection is not rare (10-30%), and chemotherapy could mitigate its impact. The possibility of detaching CLM from vessels (R1 vascular margin) has been described. A reappraisal of R1 resection is needed. METHODS: A 19-question survey regarding R1 resection for CLM was sent to hepatobiliary surgeons worldwide. Seven clinical cases were included. RESULTS: In total, 276 surgeons from 52 countries completed the survey. Ninety percent reported a negative impact of R1 resection (74% local recurrence, 31% hepatic recurrence, and 36% survival), but 50% considered it sometimes required for resectability. Ninety-one percent of responders suggested that the impact of R1 resection is modulated by the response to chemotherapy and/or CLM characteristics. Half considered the risk of R1 resection to be an indication for preoperative chemotherapy in patients who otherwise underwent upfront resection, and 40% modified the chemotherapy regimen when the tumor response did not guarantee R0 resection. Nevertheless, 80% scheduled R1 resection for multiple bilobar CLM that responded to chemotherapy. Forty-five percent considered the vascular margin equivalent to R0 resection. However, for lesions in contact with the right hepatic vein, right hepatectomy remained the standard. Detachment from the vein was rarely considered (10%), but 27% considered detachment in the presence of multiple bilobar CLM. CONCLUSIONS: A negative margin is still standard for CLM, but R1 resection is no longer just a technical error. R1 resection should be part of the modern multidisciplinary, aggressive approach to CLM.

Surgical Strategy Based on Indocyanine Green Test for Chemotherapy-Associated Liver Injury and Long-Term Outcome in Colorectal Liver Metastases.

BACKGROUND: It remains unclear whether the presence of chemotherapy-induced liver injury (CALI) or impaired liver functional reserve affects the long-term outcome. This study assessed the applicability and long-term effects of using criteria based on the indocyanine green (ICG) test results in selecting the operative procedure among patients with colorectal liver metastases (CRLM) who had a risk of CALI. STUDY DESIGN: CRLM patients who received preoperative chemotherapy including oxaliplatin and/or irinotecan prior to a curative hepatectomy between 2007 and 2017 were included. For each case, the minimum required future remnant liver volume and operative procedure were decided based on the ICG retention rate at 15 min (ICG R15). Patients with an ICG R15 > 10% and who had undergone a major hepatectomy were categorized in a marginal liver functional reserve (MHML) group. RESULTS: Overall, 161 patients were included; 77 of them had an ICG R15 > 10%, and 57 had pathological liver injury (PLI). After the median follow-up time of 30.9 months, the 5-year overall survival rate was 36.1%. The presence of an impaired ICG test result or CALI did not negatively impact the overall and recurrence-free survival outcomes. A multivariate analysis revealed that the presence of four or more nodules of liver metastases was the only independent predictor of a poor overall survival. A significantly larger proportion of patients in the MHML group (n = 37) had a 25% or larger increase in splenic volume (30 vs. 13%; P = 0.024). CONCLUSION: The presence of an impaired ICG test result or PLI did not affect the long-term outcome after individually selected operative procedure. However, patients undergoing MHML had a higher possibility of developing a > 25% splenic volume increase after hepatectomy.

Feasibility of Intraoperative Navigation for Liver Resection Using Real-time Virtual Sonography With Novel Automatic Registration System.

BACKGROUND: The clinical feasibility and usability of intraoperative ultrasonography (IOUS) tracked by computed tomography (CT) images have been proposed; however, it requires technically demanding manual registration procedure. STUDY DESIGN: A prospective study using real-time virtual sonography (RVS) with novel automatic registration system was conducted in four high-volume centers of liver resection from 2015 to 2016. The requiring time for registration of IOUS and CT images and positional error of confluence of middle hepatic venous tributaries (V8-MHV, V5-MHV) were measured in patients undergoing laparotomy. RESULTS: Automatic registration was successful in 43 of 52 enrolled patients (83%), with error ranges of 11.4 (3.1-69.4) mm for V8-MHV and 16.2 (4.3-66.8) mm for V5-MHV. Time required for total registration process was 36 (27-74) s. CONCLUSIONS: The RVS with novel automatic registration system can provide quick and easy registration and acceptable accuracy, which can promote the usage of IOUS.

Hepatopancreaticoduodenectomy for Biliary Cancer: Strategies for Near-zero Operative Mortality and Acceptable Long-term Outcome.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of hepatopancreaticoduodenectomy (HPD) for patients with biliary cancer. BACKGROUND: HPD is thought to be the only curative treatment for widespread bile duct cancer and for some advanced cases of gallbladder cancer; however, HPD has not yet been accepted as a standard operative procedure because of concerns over morbidity and mortality. METHODS: Fifty-two patients undergoing HPD were retrospectively reviewed. The patient and tumor characteristics, preoperative treatments, operative results, and survival outcomes were investigated. RESULTS: Preoperative biliary drainage and portal vein embolization were applied for all patients undergoing right-sided HPD or a left trisectionectomy. A major hepatectomy was performed in 42 patients, and a 2-stage pancreaticojejunostomy was selected in all the cases. The 90-day mortality was 0; however, 1 patient died because of a liver abscess 230 days after surgery. Postoperative significant complications (grade III or greater) and liver insufficiency were observed in 19 (37%) and 2 (3.8%) patients, respectively, and no abdominal bleeding events after the formation of a pancreatic fistula were encountered. The 5-year overall survival rate was 44.5%, and a significant difference was not observed between patients with bile duct cancer and those with gallbladder cancer. The operative procedure was switched to an HPD in 13 patients based on intraoperative findings, and the recurrence-free survival rate for these patients was poorer than that for patients who did not require a switch in operative procedure (P = 0.004). CONCLUSIONS: HPD can be safely performed using the presently reported surgical strategies with acceptable short and long-term outcomes. A precise assessment of the extent of tumor spread might improve patient outcome.

Prospective evaluation of the International Study Group for Liver Surgery definition of post hepatectomy liver failure after liver resection: an international multicentre study.

BACKGROUND: The International Study Group for Liver Surgery (ISGLS) definition of post hepatectomy liver failure (PHLF) was developed to be consistent, widely applicable, and to include severity stratification. This international multicentre collaborative study aimed to prospectively validate the ISGLS definition of PHLF. METHODS: 11 HPB centres from 7 countries developed a standardised reporting form. Prospectively acquired anonymised data on liver resections performed between 01 July 2010 and 30 June 2011 was collected. A multivariate analysis was undertaken of clinically important variables. RESULTS: Of the 949 patients included, 86 (9%) met PHLF requirements. On multivariate analyses, age ≥70 years, pre-operative chemotherapy, steatosis, resection of >3 segments, vascular reconstruction and intraoperative blood loss >300 ml significantly increased the risk of PHLF. Receiver operator curve (ROC) analysis of INR and serum bilirubin relationship with PHLF demonstrated post-operative day 3 and 5 INR performed equally in predicting PHLF, and day 5 bilirubin was the strongest predictor of PHLF. Combining ISGLS grades B and C groups resulted in a high sensitivity for predicting mortality compared to the 50-50 rule and Peak bilirubin >7 mg/dl. CONCLUSIONS: The ISGLS definition performed well in this prospective validation study, and may be the optimal definition for PHLF in future research to allow for comparability of data.

Surgical Site Infection after Hepatectomy for Hepatocellular Carcinoma.

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.