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Background: Liver resection offers substantial advantages over open liver resection (OLR) for patients with hepatocellular carcinoma (HCC) in terms of reduced intraoperative blood loss and morbidity. However, there is limited evidence comparing the indications and perioperative outcomes with the open versus laparoscopic approach for resection. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection (LLR) and OLR for HCC with clinically significant portal hypertension (CSPH)., Methods: A total of 316 HCC patients with CSPH (the presence of gastroesophageal varices or platelet count < 100,000/ml and spleen diameter > 12 cm) undergoing minor liver resection at eight centers were included in this study. To adjust for confounding factors between the LLR and OLR groups, an inverse probability weighting method analysis was performed., Results: Overall, 193 patients underwent LLR and 123 underwent OLR. After weighting, LLR was associated with a lower volume of intraoperative blood loss and the incidence of postoperative complications (including pulmonary complications, incisional surgical site infection, and paralytic ileus) compared to the OLR group. The 3-, 5-, and 7-year postoperative recurrence-free survival rates were 39%, 26%, and 22% in the LLR group and 49%, 18%, and 18% in the OLR group, respectively (p = 0.18). And, the 3-, 5-, and 7-year postoperative overall survival rates were 71%, 56%, and 44% in the LLR group and 76%, 51%, 44% in the OLR group, respectively (p = 0.87)., Conclusions: LLR for HCC patients with CSPH is clinically advantageous by lowering the volume of intraoperative blood loss and incidence of postoperative complications, thereby offering feasible long-term survival., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The influence of prolonged intermittent Pringle maneuver (IPM) on post-hepatectomy liver failure (PHLF) remains unclear. We evaluated the impact of the prolonged IPM on PHLF in patients undergoing open and laparoscopic hepatectomy., Methods: We retrospectively included 546 patients who underwent hepatectomy using IPM. The patients were divided into open (n = 294) and laparoscopic (n = 252) groups. Odds ratios for PHLF occurrence were estimated in each group according to cumulative Pringle time (CPT). The cut-off value was set at CPT of 120 min. Risk factors for PHLF were evaluated in the open and laparoscopic groups. Additionally, we analyzed the post-operative outcomes in the open and laparoscopic groups with CPT ≥ 120 min and performed propensity score matching analysis based on PFLF-associated factors., Results: In the open group, the risk of PHLF increased as CPT increased, particularly after 120 min. However, in the laparoscopic group, PHLF did not occur at less than 60 min, and the risk of PHLF was not significantly different at more than 60 min. Multivariate analysis identified CPT ≥ 120 min as an independent risk factor for PHLF in the open group (p < 0.001), but not in the laparoscopic group. Propensity score matching analysis showed that the PHLF rate was significantly lower in the laparoscopic group with CPT ≥ 120 min (p = 0.027). The post-operative transaminase levels were significantly lower in the laparoscopic group with CPT ≥ 120 min., Conclusions: Laparoscopic hepatectomy may cause less PHLF with prolonged IPM compared with open hepatectomy., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Delirium is a multifactorial and heterogeneous syndrome that is defined as acutely altered consciousness. This retrospective multicenter study evaluated the impact of postoperative delirium after liver resection for hepatocellular carcinoma (HCC) in elderly patients., Methods: Patients aged ≥75 years, who underwent curative liver resection for HCC at nine university hospitals from April 2010 to December 2017, were evaluated to compare short- and long-term outcomes between patients with and without delirium. Risk factors for delirium were determined using multivariate regression analysis., Results: The rate of postoperative delirium was 14.2% (n = 80) in the study cohort of 562 patients. Multivariate analysis revealed smoking history, hypertension, sleeping pill consumption, and open liver resection as risk factors for postoperative delirium. The rate of other causes of death was significantly higher in the delirium group than in the no-delirium group although the rate of death at 1 year due to HCC or liver failure was similar between the two groups (p = .015). The 1-year mortality rates due to vascular diseases were 71.4% and 15.4% in the delirium and no-delirium groups, respectively (p = .022). The 1-, 3-, and 5-year survival rates after liver resection were 86.6%, 64.1%, and 36.5% in the delirium group and 91.3%, 71.2%, and 56.9% in the no-delirium group, respectively (p = .046)., Conclusion: The multivariate analysis revealed the possible benefits of laparoscopic liver resection in reducing the rate of postoperative delirium after liver resection for HCC in elderly patients., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objective: This multicenter study aimed to compare the short- and long-term outcomes of laparoscopic (LRLR) versus open repeat liver resection (ORLR) for recurrent hepatocellular carcinoma (HCC) using propensity score matching (PSM). Despite the expanding indications for laparoscopic liver resection, limited data regarding the outcomes of LRLR have previously been reported., Methods: This study included patients who underwent repeat liver resection for recurrent HCC. Patients were divided into the LRLR and ORLR groups, and their short- and long-term outcomes were compared via PSM., Results: There were 256 and 130 patients in the ORLR and LRLR groups, respectively. After PSM, 64 patients were included in each group. Intraoperative blood loss was significantly less in LRLR than in ORLR (56 vs 208 ml, P < .001). Postoperative complications of Clavien-Dindo IIIa or more were significantly less in LRLR than in ORLR (3.1% vs 15.6%, P = .030). The length of hospital stay was notably shorter in LRLR than in ORLR (9 vs 12 days, P < .001). Survival rates after repeat liver resection at 1, 3, and 5 years, respectively, were comparable at 93.4%, 81.9%, and 63.5% for ORLR and at 94.8%, 80.7%, and 67.3% for LRLR (P = .623). Subgroup analysis of patients who underwent wedge resection in repeat liver resection revealed that the postoperative complication rate was notably lower in LRLR than in ORLR (7.2% vs 21.8%, P = .030)., Conclusion: LRLR for recurrent HCC is a viable option due to its better short-term outcomes and comparable long-term outcomes compared to ORLR., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Backgrounds: Liver resection for hepatocellular carcinoma (HCC) in patients with Child-Pugh class (CPC) B increases the incidence of postoperative complication and in-hospital death and decreases the disease-free survival (DFS) and overall survival (OS) compared with those with CPC A. Conversely, some selected patients possibly gained benefits for liver resection., Methods: Clinical records of 114 patients with CPC B who underwent liver resection for HCC were retrospectively reviewed. The risk of postoperative complications (Clavien-Dindo classification grade of ≥ II), postoperative recurrence, and death was analyzed., Results: Postoperative complications occurred in 36 patients (31.6%), and 2 died within 90 days postoperatively due to the liver and respiratory failure, respectively. Multivariate analysis indicated that albumin-bilirubin (ALB) grade III and extended operation time were found as independent risk factors for postoperative complications. The DFS and OS rates at 3/5 years after liver resection were 30.8%/25.3% and 68.4%/48.9%, respectively. Multivariate analysis indicated that the extended blood loss, high α-fetoprotein (AFP) level (≥ 200 ng/mL), and Barcelona Clinic Liver Cancer stage C were found to be independent risk factors for postoperative recurrence. The high AFP level was also an independent prognostic factor for OS. Patients with high AFP levels had postoperative recurrence within 2 years and a higher number of extrahepatic recurrences than those with low AFP levels (< 200 ng/mL)., Conclusion: For patients with HCC with CPC B who were scheduled for liver resection, ALBI grade III and high AFP level should be considered as unfavorable outcomes after liver resection., (© 2022. The Society for Surgery of the Alimentary Tract.)

Purpose: Tumor-infiltrating lymphocytes (TILs) may influence the prognosis of colorectal liver metastasis (CRLM). We assessed the prognostic value of evaluating TILs in the primary and metastatic sites of synchronous CRLM as well as metachronous CRLM., Methods: We examined 90 patients who underwent curative primary and liver metastasis resection for colorectal cancer. CD8 + TILs (cytotoxic T cells) or CD45RO + TILs (memory T cells) in both primary and metastatic sites were simultaneously evaluated by immunohistochemistry., Results: Fifty-one patients had synchronous CRLM, and 39 patients had metachronous CRLM. In synchronous cases, the overall survival (OS) was significantly worse in patients with low CD8 + or CD45RO + TILs in a metastatic site than in those with high CD8 + or CD45RO + TILs (P = 0.017 and P = 0.005, respectively). Multivariate analysis showed that age ≥ 65 years (P = 0.043), maximum tumor size ≥ 30 mm (P = 0.003), primary N2-3 (P = 0.019), and low CD8 + TILs in metastatic site (P = 0.046) were independent poor prognostic factors. In contrast, in metachronous cases, OS was significantly worse in patients with low CD45RO + TILs in a primary site than in those with high CD45RO + TILs (P = 0.021). CD45RO + TILs in a primary site (P = 0.044) were determined to be independent prognostic factor on multivariate analysis., Conclusions: The immune microenvironment between synchronous and metachronous CRLM might be different, and these differences may affect its prognosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We investigated the detailed recurrent sites after wedge liver resection for primary hepatocellular carcinoma (HCC)., Methods: We retrospectively reviewed 278 patients with primary HCC who underwent curative liver resection between 2000 and 2016. Recurrent sites were divided into four groups: around the initial HCC (segmental recurrence), within the same section as the primary HCC (sectional recurrence), within the same lobe as the primary HCC (lobar recurrence), and contralateral or extrahepatic recurrence (extra recurrence)., Results: Recurrence was observed in 101 of 147 patients who underwent wedge resection. At first recurrence, segmental recurrence was observed in 18 patients (17.8%), while 28 patients (27.7%) were with sectional recurrence and 48 patients (47.5%) were with lobar recurrence. However, the cumulative recurrent sites of each patient showed extra recurrence in 53 patients (52.5%) at initial recurrence, 79 patients (78.2%) until the second recurrence, 89 patients (88.1%) until the third recurrence, 94 patients (93.0%) until the fourth, and 96 patients (95.0%) until the fifth recurrence., Conclusion: Some intrahepatic recurrence after wedge resection might have been avoided if anatomic resection had been performed instead. However, the number of contralateral or extrahepatic recurrences increased with the number of recurrences., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Organ/space surgical site infection (SSI) is one of the most common complications of liver resection, with significant impact on morbidity and mortality, so patients at high risk should be identified early. This study aimed to determine whether pre- and postoperative C-reactive protein (CRP) levels could predict organ/space SSIs., Methods: The hospital records of consecutive patients who underwent hepatectomy without biliary reconstruction at our institutions between 2008 and 2015 were reviewed retrospectively. Preoperative, intraoperative, and postoperative variables were compared between patients with or without organ/space SSIs. Its risk factors were also determined., Results: Among 443 identified patients, 55 cases (12.5%) developed organ/space SSIs; they more frequently experienced other complications and bile leakage (47.3% vs. 16.6%, p = 0.001; 40.0% vs. 8.5%, p < 0.001, respectively). Postoperative CRP elevation from postoperative day (POD) 3 to 5 was significantly more frequent in the SSI group (21.8% vs. 4.9%, p < 0.001). Multivariate analysis identified preoperative CRP ≥ 0.2 mg/dL (odds ratio (OR), 2.01, p = 0.044], preoperative cholangitis (OR, 15.7; p = 0.020), red cell concentrate (RCC) transfusion (OR, 2.61, p = 0.018), bile leakage (OR, 9.51; p < 0.001), and CRP level elevation from POD 3 to 5 (OR, 3.81, p = 0.008) as independent risk factors for organ/space SSIs., Conclusions: Preoperative CRP elevation and postoperative CRP trajectory are risk factors for organ/space SSIs after liver resection. A prolonged CRP level elevation at POD 5 indicates its occurrence. If there were no risk factors and no CRP elevation at POD 5, its presence could be excluded., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC)., Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups., Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group., Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver., Competing Interests: None of the other authors have potential conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Background: Liver regeneration after liver resection plays an important role in preventing posthepatectomy liver failure. In this study, we aimed to evaluate and compare the impact of laparoscopic liver resection (LLR) and open liver resection (OLR) on liver regeneration., Methods: Patients who underwent curative anatomical liver resection for hepatocellular carcinoma, cholangiocellular carcinoma, and colorectal liver metastases at our institution between January 2010 and December 2018 were included in this study. The patients were divided into the OLR and LLR groups. Preoperative liver volume (PLV), future remnant liver volume, resected liver volume (RLV), liver volume at 1 month after the surgery, and liver volume at 6 months after the surgery were calculated. The liver regeneration rate was defined as the increase in the rate of RLV, and the liver recovery rate was defined as the rate of return to the PLV., Results: The study included 72 patients. Among them, 43 were included in the OLR group and 29 were included in the LLR group. No differences were observed in the baseline characteristics and surgical procedures between the two groups. Moreover, no significant difference was observed in the liver regeneration rate at 1 month after the surgery (OLR vs. LLR: 68.9% vs. 69.0%, p = 0.875) and at 6 months after the surgery (91.8% vs. 93.2%, p = 0.995). Furthermore, the liver recovery rates were not significantly different between the two groups at 1 month after the surgery (90.3% vs. 90.6%, p = 0.893) and at 6 months after the surgery (96.9% vs. 98.8%, p = 0.986)., Conclusion: Liver regeneration after liver resection is not affected by the type of surgical procedure and both laparoscopic and open procedures yield similar regeneration and recovery rates., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The prognosis of highly advanced unresectable hepatocellular carcinoma (HCC) with a portal vein tumor thrombus (PVTT) is poor. There are currently no reports of long-term survival for up to 5 years in patients with advanced HCC who were treated with sorafenib. We describe a patient with Vp4 HCC who was treated with a sorafenib-based multidisciplinary treatment and experienced long-term survival, which may be the longest survival to date. A man in his late 60 s presented with general fatigue. Eight years previously, he received interferon monotherapy for chronic hepatitis C for 48 weeks and achieved a sustained virological response. He was diagnosed with a PVTT (Vp4) with diffuse-type HCC in the S6 lobe of the liver. He received hepatic arterial infusion of chemotherapy using 5-fluorouracil and cisplatin. Because of the occurrence of adverse effects, he was placed on sorafenib treatment. The treatment was effective and the HCC reduced. However, after 3 years of treatment, a 2-cm HCC was observed in the S5 lobe, and the patient underwent laparoscopic partial hepatectomy. After the operation, he continued to receive sorafenib, with no obvious recurrence, and survived for over 108 months after the first treatment. There are currently no reported cases of long-term progression-free survival by sorafenib for five years in patients of Vp4 HCC. In conclusion, we report a case of longest survival of a patient with Vp4 HCC treated with sorafenib-based multidisciplinary treatment., (© 2022. Japanese Society of Gastroenterology.)

Background: This study aimed to determine the risk factors for severe postoperative complications in patients undergoing pure laparoscopic liver resection (LLR) for tumors in the right posterosuperior (PS) segments., Methods: The study included 289 patients who underwent parenchyma-sparing pure LLR for tumors in the right PS segments at eight treatment centers between January 2009 and December 2019., Results: Multivariate analysis revealed tumor size ≥3 cm (P = .016), segmentectomy (P = .044), and liver cirrhosis (P = .029) as independent risk factors for severe postoperative complications. The severe complication rates (2.7% vs 12.1%, P = .0025), median intraoperative blood loss (100 mL vs 150 mL, P = .001), and median operation time (248 minutes vs 299.5 minutes, P = .0013) were lower in the patients without all these three risk factors than those with at least one risk factor. The median length of postoperative hospital stay was shorter in patients with no risk factors than those with at least one risk factor (9 days vs. 10 days, P = .001)., Conclusions: Tumor size ≥3 cm, segmentectomy, and liver cirrhosis were the risk factors for severe postoperative complications after parenchyma-sparing pure LLR for tumors in the right PS segments. Patients without these three risk factors would be appropriate candidates for safely performing parenchyma-sparing pure LLR in the right PS segments at the outset., (© 2022 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Late-onset biliary complications (LBC) after pancreatoduodenectomy (PD) can be serious. This study aimed to clarify the frequency and risk factors of severe LBC after PD., Methods: We defined LBC as biliary complications occurring 3 months after PD and severe LBC as cases that required intensive care. A total of 318 patients who underwent PD between 2010 and 2018 with at least 1 year of postoperative follow-up were evaluated., Results: Hospitalization for severe LBC was required in 59 patients (19%), of whom 20 had liver abscesses (6.3%); 18, acute cholangitis (5.7%); 12, biliary stones (3.8%); and 21, biliary strictures (6.6%). Interventional radiological or endoscopic treatment was required in 32 patients (10%), of whom 9 had a benign primary disease with biliary stones and/or strictures. Thirteen of the remaining 23 patients with a malignant primary disease had liver abscesses and cholangitis. Significant independent risk factors for severe LBC in patients with malignant primary disease were recurrence around the hepaticojejunostomy (odds ratio 6.5, P = 0.013) and chemotherapy (odds ratio 13.5, P < 0.001)., Conclusions: Severe LBC after PD may occur regardless of whether the primary disease is benign or malignant. The course of severe LBC differs according to the primary disease, and therefore, appropriate follow-up and optimal treatment should be recommended according to the condition of the patient and the disease state., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Purpose: The effects of subcuticular sutures on postoperative and cosmetic outcomes in patients who underwent liver resection have not been well studied. Here, we investigated the advantages of subcuticular suture compared to skin stapler regarding open liver resection., Methods: We assessed 342 patients who underwent liver resection at Nara Medical University between 2008 and 2015. They were divided into two groups: subcuticular suture and staple groups. Baseline characteristics and perioperative outcomes were retrospectively compared using one-to-one propensity score matching analysis., Results: In this period, 179 patients underwent skin closure with subcuticular sutures and 163 patients underwent skin closure with staples. After propensity matching, 85 pairs of cases were matched. The incidence of wound infection was similar in the two groups (3.5% in the subcuticular suture group and 9.4% in the staple group; p = 0.119). The length of hospital stay was significantly shorter in the subcuticular suture group than in the staple group (10 days vs 15 days; p < 0.001). In addition, the rate of patients who were discharged within 7 days after surgery was statistically higher in the subcuticular group (21.1% vs 3.5%, p = 0.001). Hypertrophic scar 6 months after surgery was significantly less frequent in the subcuticular group (9.4% vs 25.9%, p = 0.010)., Conclusion: Subcuticular sutures might be advantageous for liver surgery reducing length of hospital stay and proportion of hypertrophic scar., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Laparoscopic liver resection for hepatic lesions is increasingly performed worldwide. However, parenchyma-sparing laparoscopic liver resection for hepatic lesions in the right posterosuperior segments is very technically demanding. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection and open liver resection for hepatic lesions in the right posterosuperior segments., Methods: In total, 617 patients who underwent liver resection of hepatic lesions in the right posterosuperior segments (segment Ⅶ or Ⅷ) at 8 centers were included in this study. We lessened the impact of confounders through propensity score matching, inverse probability weighting, and double/debiased machine learning estimations., Results: After matching and weighting, the imbalance between the 2 groups significantly decreased. Compared with open liver resection, laparoscopic liver resection was associated with a lower volume of intraoperative blood loss and incidence of postoperative complications in the matched and weighted cohorts. After surgery, the incidence of pulmonary complication and cardiac disease was lower in the laparoscopic liver resection group than in the open liver resection group in both the matched and weighted cohorts. The odds ratios of laparoscopic liver resection for postoperative complications in the matched and weighted cohorts were 0.49 (95% confidence interval, 0.29-0.83) and 0.40 (95% confidence interval, 0.25%-0.64%), respectively. The double/debiased machine learning risk difference estimator for postoperative complications of laparoscopic liver resection was -19.8% (95% confidence interval, -26.8% to -13.4%)., Conclusion: Parenchyma-sparing laparoscopic liver resection for hepatic lesions in the right posterosuperior segments had clinical benefits, including lower volume of intraoperative blood loss and incidence of postoperative complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although the prognosis of patients experiencing recurrences after surgery for pancreatic cancer is extremely poor, patients who develop recurrence in the lung have a better prognosis compared to other types of recurrence. We performed a histo-immunological analysis of the metastatic specimens to identify specific features of this patient subgroup., Methods: We performed immunohistochemistry for CD4+, CD8+, CD45RO+, Foxp3, and PD-L1 in the lung (n = 22), peritoneal (n = 18), and liver (n = 6) metastases of pancreatic cancer. As microenvironmental and immunonutritional investigations, the tumor-stroma ratio and prognostic nutritional index (PNI) were utilized in the integrative analysis of immunological features., Results: We identified significantly increased tumor-infiltrating CD4+, CD8+, and CD45RO+ cells in lung metastasis, compared with peritoneal and liver metastases (lung vs. peritoneum/liver, CD4: P < 0.001/P = 0.015, CD8: P < 0.001/P = 0.038, CD45RO: P = 0.022/P = 0.012). The CD8/Foxp3 ratio was higher in the lung than in the liver (P = 0.024). PD-L1 expression was significantly higher in lung metastasis than in peritoneal metastasis (P = 0.010). Furthermore, we found that lung metastasis had fewer cancer stroma than peritoneal metastasis (P < 0.001). A higher PNI was observed in patients with lung metastasis, and PNI was positively correlated with tumor-infiltrating lymphocytes in metastatic sites., Conclusion: We identified that lung metastasis revealed an immunologically "hot" tumor with increased TILs and PD-L1 expression. This specific feature suggests that patients with lung metastasis can be candidates for immunotherapy, such as immune checkpoint inhibitors; therefore, our study provides a framework for developing individualized treatment strategies for this patient subgroup., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Adjuvant chemotherapy for resectable colorectal liver metastasis (CRLM) is widely used, but its efficacy lacks clear evidence. This retrospective cohort study investigated the effectiveness of neoadjuvant chemotherapy (NAC) compared to upfront surgery for CRLM., Methods: Data from patients with resectable CRLM were analyzed. Short-term outcomes and long-term prognosis were analyzed using propensity score matching. CRLM was stratified according to the H-classification (H1 and H2), and the effectiveness of adjuvant chemotherapy was analyzed in each group., Results: We analyzed 599 cases that were matched into an NAC group (n = 136) and an upfront surgery group (n = 136). The proportion of synchronous metastases, H2-classification, and postoperative chemotherapy rate did not differ between the groups. Overall survival (OS) after initial treatment was significantly worse in the NAC group than in the upfront surgery group (P = 0.029). The 5-, 7-, and 10-year OS rates for H1 patients were significantly better in the upfront surgery group than in the NAC group (64%, 51%, and 44% vs. 50%, 31%, and 18%, respectively) (P = 0.004)., Conclusion: Patients with resectable CRLM should undergo upfront surgery, because NAC did not improve OS after initial treatment in these patients., (© 2021. The Society for Surgery of the Alimentary Tract.)

Purpose: The efficacy of pre or postoperative chemotherapy for resectable colorectal cancer liver metastases (CRLM) is disputed. This study aimed to examine the risk factors for time to surgical failure (TSF) and analyze the efficacy of pre or postoperative chemotherapy prior to liver resection for CRLM., Methods: The clinicopathological factors of 567 patients who underwent initial hepatectomy for CRLM at 7 university hospitals between April 2007 and March 2013 were retrospectively analyzed. The prognostic factors were identified and then stratified into two groups according to the number of preoperative prognostic factors: the high-score group (H-group, score 2-4) and the low-score group (L-group, score 0 or 1)., Results: Patients who experienced unresectable recurrence within 12 months after initial treatment had a significantly shorter prognosis than other patients (p < 0.001). Multivariate analysis identified age ≥ 70 (p = 0.001), pT4 (p = 0.015), pN1 (p < 0.001), carbohydrate antigen 19-9 ≥ 37 U/ml (p = 0.002), Clavien-Dindo grade ≥ IIIa (p = 0.013), and postoperative chemotherapy (p = 0.006) as independent prognostic factors. In the H-group, patients who received chemotherapy had a better prognosis than those who did not (p = 0.001)., Conclusion: Postoperative chemotherapy is beneficial in colorectal cancer patients with more than two of the following factors: age ≥ 70, carbohydrate antigen 19-9-positivity, pT4, and lymph node metastasis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Non-invasive biomarkers detected preoperatively are still inadequate for treatment decision making for patients with intrahepatic cholangiocarcinoma (ICC). In this study, we analyzed preoperative findings to establish a novel preoperative staging system (PRE-Stage) for patients with ICC. Methods: The clinical data of 227 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals were analyzed. Results: Cox proportional hazards regression analysis of survival revealed that a CRP−albumin−lymphocyte index < 3, central tumor location, and CA19-9 level > 40 U/mL were prognostic factors among the preoperatively obtained clinical findings (hazard ratios (HRs) of all three factors for disease-specific survival (DSS) and disease-free survival (DFS: 2.4−3.3 and 1.7−2.9; all p < 0.05). The PRE-Stage was developed using these three prognostic factors, and it was able to significantly predict DSS and DFS when the patients were stratified into four stages (p < 0.05). In addition, the PRE-Stage resulted in similar HRs as those of the Liver Cancer Study Group of Japan (LCSGJ) stage (HRs for DSS: PRE-Stage, 1.985; LCSGJ stage, 1.923; HRs for DFS: LCSGJ stage, 1.909, and PRE-Stage, 1.623, all p < 0.05). Conclusion: The PRE-Stage demonstrated similar accuracy in predicting the prognosis of ICC as that of the LCSGJ stage, which is based on postoperative findings. The PRE-Stage may contribute to appropriate treatment decision making.

Background: Restrictive pulmonary dysfunction (RPD) is a risk factor for perioperative complications during gastrointestinal surgery. We hypothesized that high airway pressure due to RPD results in increased intraoperative blood loss during liver surgery. Thus, we investigated the effects of RPD on perioperative outcomes for liver resection., Methods: This study included 496 patients who underwent curative liver resection at our hospital between April 2009 and April 2020. Perioperative outcomes for the RPD and control groups were compared. Restrictive pulmonary dysfunction was defined as % vital capacity <80%., Results: Forty-one patients (8.3%) had RPD. No significant differences were observed in intraoperative blood losses (440 mL vs 320 mL, P = .340), overall complication rates (29.3% vs 31.2%, P = .797), or pulmonary complication rates (4.9% vs 9.0%, P = .286) between the RPD and control groups. In the 256 patients who underwent anatomical liver resection, 18 patients (7.0%) had RPD. The intraoperative blood loss was significantly higher in the RPD group (925 mL vs 456 mL, P = .013), but no differences in the overall complication rates (44.4% vs 37.3%, P = .528) or pulmonary complication rates (11.1% vs 10.5%, P = .589) between the two groups were detected. A multivariate analysis showed that RPD was an independent risk factor for intraoperative blood loss ≥500 mL during anatomical liver resection (odds ratio 4.132; 95% confidence interval 1.135-15.045; P = .031)., Discussion: Restrictive pulmonary dysfunction may be a risk factor for intraoperative blood loss during anatomical liver resection, which requires exposure of the main hepatic vein.

Background: Synchronous colorectal liver metastasis (SCRLM) is at an advanced tumor stage and requires multidisciplinary treatments. Neoadjuvant chemotherapy (NAC) is thought to be an effective treatment modality, but its prognostic impact is still unclear., Materials and Methods: Patients with resectable SCRLM presented to eight university hospitals between 2007 and 2017 were retrospectively reviewed. Propensity score matching (PSM) was performed to adjust baseline characteristics between patients who received NAC with those who underwent up-front hepatectomy. The prognostic impact of NAC was then evaluated., Results: The cohort comprised of 320 patients: 151 patients received NAC and the remaining 169 patients underwent up-front hepatectomy. After a 1:1 ratio of PSM, 102 patients per group were selected. Within the PSM cohort, 66% patients had multiple liver tumors, with 15% having five or more liver tumors. The median survival (95% confidence interval) periods for patients with and without NAC in the PSM cohort were 88.5 (68.4 - not reached) and 84.2 (52.1 - not reached) months, respectively (P = 0.51). On multivariate analysis, the postoperative events in these patients including operative complications and use of adjuvant chemotherapy after hepatectomy were prognostic factors with hazards (95% confidence interval) being 1.88 (1.18-2.98) and 0.65 (0.42-1.01), respectively., Conclusion: This PSM study was restricted to patients with SCRLM and relatively advanced tumor stagings. NAC did not show any significant prognostic impact. While operative complications had a significant prognostic impact, use of adjuvant chemotherapy after hepatectomy had only a marginal prognostic impact. Reconsideration of indications for NAC is needed., (Copyright © 2021 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: Primary tumor location of colon cancer has been reported to affect the prognosis after curative resection. However, some reports suggested the impact was varied by tumor stage. This study analyzed the prognostic impact of the sidedness of colon cancer in stages II, III, and liver metastasis after curative resection using propensity-matched analysis., Methods: Right-sided colon cancer was defined as a tumor located from cecum to splenic flexure, while any more distal colon cancer was defined as left-sided colon cancer. Patients who underwent curative resection at Nara Medical University hospital between 2000 and 2016 were analyzed., Results: There were 110 patients with stage II, 100 patients with stage III, and 106 patients with liver metastasis. After propensity matching, 28 pairs with stage II and 32 pairs with stage III were identified. In the patients with stage II, overall survival (OS) and recurrence-free survival (RFS) were not significantly different for right- and left-sided colon cancers. In the patients with stage III, OS and RFS were significantly worse in right-sided colon cancer. In those with liver metastasis, OS of right-sided colon cancer was significantly worse than left-sided disease, while RFS was similar. Regarding metachronous liver metastasis, the difference was observed only in the patients whose primary colon cancer was stage III. In each stage, significantly higher rate of peritoneal recurrence was found in those with right-sided colon cancer., Conclusion: Sidedness of colon cancer had a significant and varied prognostic impact in patients with stage II, III, and liver metastasis after curative resection.

Background: Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM)., Methods: We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated., Results: The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p < 0.001), primary CRC N2-3 (p = 0.049), and high-CD200 expression (p = 0.004). Furthermore, CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes in CRLM were significantly higher in the low-CD200 group than in the high-CD200 group (p = 0.005, p = 0.001, and p < 0.001, respectively). In addition, patients who had received preoperative chemotherapy had higher CD200 expression than those who had not received preoperative chemotherapy, and OS was significantly worse in patients in the high-CD200 group who had received preoperative chemotherapy., Conclusions: CD200 expression was an independent prognostic factor in CRLM. CD200 may play a critical role in tumor immunity in CRLM, and can therefore be used as a potential therapeutic target in CRLM., (© 2021. Society of Surgical Oncology.)

Background: Although postoperative pulmonary complications (PPCs) are one of the common complications after liver surgery and might be avoided with the use of a laparoscopic approach, few reports have focused on the comparison of PPCs between laparoscopic liver resection (LLR) and open liver resection (OLR). The aim of this study was to clarify the effect of LLR on PPCs., Methods: The study included 307 patients who underwent liver resection, excluding biliary reconstruction, at our institution between 2014 and 2018. Patients were divided into the OLR and LLR groups. The perioperative outcomes and PPCs were compared between the two groups using propensity score matching. On day 3 after liver surgery, all patients had chest radiography to confirm the presence of pleural effusion, including cases that required thoracentesis, and pneumonia., Results: Of the 307 patients, 172 and 135 patients were included in OLR and LLR groups, respectively. After propensity score matching, 65 patients were included in each group. Compared with the matched OLR group, the matched LLR group had significantly lower intraoperative blood loss (P < 0.001); rate of intraoperative blood transfusion (P = 0.011); overall PPCs (P = 0.032); and number of cases with chest radiography-confirmed pleural effusion (P = 0.048), pleural effusion requiring thoracentesis (P = 0.029), and pneumonia (P = 0.012). Moreover, postoperative hospital stay was significantly shorter in the matched LLR group than in the matched OLR group., Conclusions: Compared with OLR, LLR might be a better surgical approach to avoid PPCs.

Background: The aim of this study was to clarify the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with chronic kidney disease (CKD)., Methods: In all, 204 patients who underwent primary liver resection for HCC between 2011 and 2019 were analyzed. Short-term and long-term outcomes were compared between the CKD and control groups. The CKD group was defined by a preoperative estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m 2 and chronic kidney disease Stage 3B or higher., Results: Twenty-eight patients (13.7%) had CKD. No significant differences were observed in the overall complication rates between the groups (46.4% vs. 34.7% p = 0.229). The incidence of bile leakage was significantly higher in the CKD group than in the control group (14.3% vs. 4.0% p = 0.048), and the median postoperative hospital stay was significantly longer in the CKD group (11 vs. 9 days p = 0.031). No significant differences were found in the disease-free survival between the two groups (p = 0.763), but overall survival (OS) was significantly worse in the CKD group than in the control group (p = 0.022). In the multivariable analysis, a CKD diagnosis (hazard ratio, 2.261; 95% confidence interval (CI), 1.139-4.486 p = 0.020) was identified as an independent poor prognostic factor for OS. The percentage of patients who died from cardiovascular disease was significantly higher in the CKD group (27.3% vs. 2.3% p = 0.023)., Conclusions: Liver resection for HCC in CKD patients is associated with acceptable perioperative outcomes. However, cardiovascular disease may negatively affect the OS of CKD patients after liver resection.

Liver parenchymal transection is the most important process in laparoscopic liver resection (LLR). Various surgical methods and devices for LLR have been applied including the cavitron ultrasonic surgical aspirator, ultrasonic scalpel, and staplers. Very few reports have investigated the clamp--crush technique for LLR.1 , 2 Current study shows a clamp-crush technique for LLR and evaluates its perioperative outcomes. The clamp-crush technique was performed using simple forceps and the Pringle maneuver under a low central venous pressure. The vessels that remained after crushing were clipped if they were thick; or removed with an ultrasonic cutting-coagulation system if they were thin. Sixty-one LLRs were performed using the clamp-crush technique. Pathological cirrhosis was observed in 22 patients (36.0%). The types of resection were as follows: 31 wedge resections (50.8%), 11 segmentectomies (19.0%), 9 sectionectomies (14.8%), and 10 hemihepatectomies (16.4%). The intraoperative blood loss was 62 ml; the surgical duration was 272 min. The postoperative major complication (Clavien-Dindo ≥ IIIa) rate was 4.9%. The median hospital stay was 8 days (range = 4-53 days). A 76-year-old female underwent right LLR for a 9-cm HCC. The right hepatic artery and portal vein were dissected separately. After mobilizing the liver, parenchymal transection was performed using the clamp-crush technique. The middle hepatic vein was totally exposed. Intraoperative blood loss was 32 ml and the surgical duration was 5 h 32 min with no postoperative complications. The clamp-crush technique is safe and feasible for LLR and could contribute to quick parenchymal transection and flattening of the transection plane.

Background: Postoperative delirium was reported to be associated with increased postoperative mortality after liver resection. Therefore, it is crucial to prevent postoperative delirium in such cases. Ramelteon, an agonist of melatonin receptor has been suggested to be useful for preventing delirium. The aim of this study was to examine whether ramelteon is effective at preventing delirium after elective liver resection., Methods: The cases of patients who underwent liver resection at Nara Medical University (Nara, Japan) between January 2014 and August 2018 were analyzed. During the period from January 2017 to August 2018, ramelteon was prospectively administered to patients who underwent liver resection [8 mg/day on the day before surgery and on postoperative days 1 to 3] (ramelteon group), whereas ramelteon was not administered during the period from January 2014 to December 2016 (control group). The perioperative outcomes of the two groups were compared., Results: There were 120 patients in the ramelteon group and 186 patients in the control group. No significant intergroup differences in background factors, including age, gender, and preoperative serological laboratory data, were detected. The incidence of postoperative delirium was significantly lower in the ramelteon group (5.8% vs. 15.1%, P = 0.035). Multivariate analysis revealed that being aged ≥75 (P = 0.002), being male (P = 0.020), cardiovascular disease (P = 0.023), blood loss ≥1000ml (P = 0.001) and the absence of ramelteon treatment (P = 0.046) were independent risk factors for postoperative delirium., Conclusion: The administration of ramelteon might reduce the risk of postoperative delirium after elective liver resection., Competing Interests: The authors have declared that no competing interests exist.

Background/purpose: Aeromonas hydrophila can cause lethal infectious complications after surgery. There have been no large cohort studies of this specific to the hepato-biliary-pancreatic (HBP) field. We investigate the postoperative influence of A hydrophila infection after HBP surgery., Methods: We retrospectively reviewed patients who underwent HBP surgery between 2008 and 2017 at eight university hospitals. Patients with A hydrophila isolation during perioperative management were extracted, and their postoperative courses were investigated., Results: Bacterial culture examination of 10 074 patients was performed as perioperative management. Among them, 76 patients (0.75%) had A hydrophila isolation, most of whom underwent pancreatoduodenectomy (n = 38) or hepatectomy with biliary reconstruction (n = 14). There were seven mortalities after these two procedures (13.5%), five within 3 days after the onset of infection. Bile (n = 48) and abdominal drainage fluid (n = 29) were major sites of A hydrophila isolation. Typical prophylactic antibiotics, cefazolin or flomoxef, were mostly resistant. There was no mortality among patients that received sensitive antibiotics prophylactically., Conclusions: Isolation of A hydrophila was low in our cases of HBP surgery, but the condition of some patients deteriorated rapidly by this infection. Although there could be several bacterial infections during management of HBP surgery, A hydrophila should not be overlooked. Preparation of appropriate prophylactic antibiotics may prevent or reduce mortality., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The extrahepatic surgical technique in liver resection can be divided into glissonean pedicle transection and glissonean separated transection approaches. In this study, we compared remnant liver function and liver regeneration involving the Spiegel lobe between these two approaches regarding Spiegel lobe-preserving left hepatectomy., Methods: We enrolled 31 patients who underwent Spiegel lobe-preserving left hepatectomy for malignant hepatobiliary diseases between April 2008 and January 2020. The postoperative Spiegel lobe volume was measured using a volume analyzer at 3 and 6 months postoperatively., Results: Of the 31 patients, 22 and 9 were included in the glissonean separated transection and glissonean pedicle transection groups, respectively. There was no significant between-group difference in the preoperative Spiegel lobe volume. However, the volumes at 3 and 6 months postoperatively were significantly larger in the glissonean pedicle transection group than in the glissonean transection group (29.92 mL vs. 13.00 mL; P < 0.001 and 28.43 mL vs. 15.01 mL; P < 0.001, respectively). There was no significant between-group difference in postoperative remnant liver function., Conclusions: The postoperative Spiegel lobe volume was larger, and liver regeneration was better with the glissonean pedicle transection approach because of transection for Spiegel branch of the portal vein. It is desirable to preserve Spiegel branch in possible cases when surgeons select the glissonean separated transection approach based on the location and size of the tumors.

A 64-year-old man was diagnosed with cholangiocellular carcinoma based on preoperative computed tomography and magnetic resonance imaging and underwent laparoscopic segmentectomy (Segment 8) of the liver for radical operation. Pathological examination revealed the presence of an undifferentiated carcinoma with osteoclast-like giant cells, which were categorized as T3N0M0 and Stage III based on the third English edition of the Japanese classification of liver cancer. The patient was treated with three courses of combination chemotherapy, which included gemcitabine (1000 mg/m 2 ) and cisplatin (25 mg/m 2 ), as well as S-1 (120 mg/day) for adjuvant chemotherapy. At two months after the operation, CT revealed multiple liver- and lung metastases. Thereafter, the patient was prescribed the molecularly targeted drug, lenvatinib (12 mg/day). However, lenvatinib was not effective, as evident by the extension of several metastases. Testing for microsatellite instability was negative. The patient died 5 months after the operation. We experienced a case of primary undifferentiated carcinoma with osteoclast-like giant cells in the liver showed rapidly developing multiple metastases after curative liver resection., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Japan Society of Clinical Oncology 2020.)

Background : With an aging population, more elderly patients are being considered for hepatic resection for hepatocellular carcinoma (HCC). This study aimed to evaluate postoperative outcomes including liver regeneration after major hepatectomy for HCC in the elderly. Methods : We assessed 41 patients who underwent major hepatectomy (≥3 segments) at our institute between 2000 and 2013. Patients were divided into two age groups, elderly group (age ≥70 years, n  = 23) and younger group (age <70 years, n  = 18). Clinicopathological data and outcomes were retrospectively compared. To evaluate the effect of aging on liver regeneration, we measured liver volumes preoperatively and at 1 and 6 months after liver resection using a 3D simulation imaging system. Results : Overall and major complications after hepatectomy were not different between elderly and younger groups, and no case of mortality was recorded. Moreover, recurrence-free and overall survivals were similar in both groups. With regard to liver regeneration, no differences were observed between elderly and younger groups at 1 and 6 months after liver resection. Baseline liver functions were comparable between the groups. Furthermore, the only factor associated with liver regeneration was resected liver volume ( R 2  = 0.631, p  < 0.001). Age was not correlated with liver regeneration rate ( R 2  = 0.00537, p  = 0.695). Conclusions : Liver regeneration after major hepatectomy for HCC was not affected by age and that resected liver volume is an important factor for liver regeneration. Short- and long-term outcomes after major hepatectomy were similar in elderly and younger patients.

Background: The frequency of liver resection in elderly patients has been increasing. However, data are limited regarding the safety of laparoscopic liver resection (LLR) compared with that of open liver resection (OLR) for hepatocellular carcinoma (HCC) in elderly patients. The present study aimed to compare short-term outcomes between LLR and OLR in elderly patients with HCC using propensity score matching., Methods: The study included 630 patients (age, ≥ 75 years) who underwent liver resection for HCC at nine liver centres between April 2010 and December 2017. Patients were divided into LLR and OLR groups, and perioperative outcomes were compared between the groups. In addition, subgroup analysis was performed according to age (75-79 and ≥ 80 years)., Results: Of the 630 patients, 221 and 409 were included in the LLR and OLR groups, respectively. After propensity score matching, 155 patients were included in each group. Intraoperative blood loss and the transfusion, post-operative overall complication and major complication rates were lower in the matched LLR than the matched OLR group (P < 0.001, P = 0.004, P < 0.001 and P < 0.001, respectively). Moreover, post-operative pulmonary and cardiovascular complications were less frequent in the matched LLR group (P = 0.008 and P = 0.014, respectively). In subgroup analysis, among octogenarians, the post-operative major complication rate was lower and hospital stay was shorter in the matched LLR than the matched OLR group (P < 0.001 and P < 0.001, respectively)., Conclusion: LLR for HCC is associated with good short-term outcomes in patients aged ≥ 75 years compared with OLR. LLR is safe and feasible in selected octogenarians with HCC.

Background/aim: The aim of this study was to evaluate whether modern chemotherapy has changed characteristics of actual five-year survivors after liver resection for colorectal liver metastasis (CRLM)., Patients and Methods: The records of 210 patients, who underwent curative liver resection for CRLM at our institution between January 1990 and May 2014, were reviewed. The patients treated before 2004 when modern chemotherapy was not introduced were compared with the patients treated after 2005., Results: Actual five-year survivor rates were significantly higher after 2005 (33.3% vs. 49.0%, p=0.022). Preoperative characteristics of actual five-year survivors were not different. The median survival time after non-resectable recurrence was significantly longer after 2005 (20.3 vs. 8.7 months, p=0.002). The proportion of 5-year survivors with recurrent site was significantly higher after 2005 (34.0% vs. 10.5%, p=0.019)., Conclusion: Actual five-year survivors have increased by modern chemotherapy. However, approximately one-third of them were not cured., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: von Willebrand factor (VWF) is synthesised in vascular endothelial cells and released into the plasma as unusually large VWF multimers (UL-VWFMs). Sinusoidal endothelial cells are a major target of ischaemia-reperfusion injury due to liver surgery. This study aimed to clarify the effect of hepatectomy on UL-VWFMs., Materials and Methods: Thirty-five patients who underwent hepatectomy were eligible for the study. Plasma ADAMTS13 activity and VWF antigen levels were measured by enzyme-linked immunosorbent assay and multimer analysis of plasma VWF was performed according to Ruggeri and Zimmerman's method. For analyses, patients were categorised according to UL-VWFM positivity after hepatectomy., Results: Plasma ADAMTS13 activity significantly decreased from 61.0% (27.7%-126.2%) before operation to 37.4% (20.2%-71.4%) on postoperative day 7 (p < 0.001). Plasma VWF antigen levels significantly increased from 172.1% (80.5%-412.8%) before operation to 361.0% (154.7%-745.8%) on postoperative day 2, which remained high until postoperative day 7 (p < 0.001). Seven patients remained UL-VWFMs-negative and 22 patients became UL-VWFMs-positive after operation. Pringle's maneuver duration was significantly longer and blood loss volume was significantly higher in the UL-VWFMs-positive group (p = 0.001 and p = 0.003, respectively). By multivariable analysis, Pringle's maneuver duration [odds ratio 1.049, 95% confidence interval (CI) 1.001-1.098; p = 0.043] was significantly associated with increased UL-VWFMs level after hepatectomy. UL-VWFMs index was significantly correlated with Pringle's maneuver duration (r = 0.444, p = 0.017)., Conclusions: Plasma UL-VWFMs levels increased after hepatectomy due to ischaemia-reperfusion injury with Pringle's maneuver., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Herpesvirus entry mediator (HVEM) has been suggested to play various roles in cancer biology. The authors report that HVEM expression in tumor cells is associated with a reduction in the number of tumor-infiltrating lymphocytes and a poor prognosis after surgical resection in various human gastrointestinal cancers. This study aimed to clarify the clinical significance of HVEM expression in human colorectal liver metastasis (CRLM)., Methods: This study examined the cases of 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. The median follow-up period was 50.2 months. Immunohistochemical staining was performed using antibodies against HVEM, CD4, CD8, and CD45RO., Results: High HVEM expression was observed in 49 patients (47.1%) with CRLM. Expression of HVEM was not associated with age, gender, administration of preoperative chemotherapy, tumor size, number of tumors, or histologic differentiation. The high-HVEM group exhibited significantly worse overall survival (OS) than the low-HVEM group (P = 0.002). Multivariate analysis showed that high HVEM expression in CRLM, age of 70 years or older, and having five or more tumors are independent poor prognostic factors for OS (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.41-7.93; P = 0.006). The number of tumor-infiltrating CD8+ and CD45RO+ T cells was significantly lower in the high-HVEM group than in the low-HVEM group. High HVEM expression in primary colorectal cancer was significantly associated with synchronous CRLM, but not with metachronous CRLM., Conclusions: Tumor HVEM expression might play a critical role in CRLM.

Background: Among all laparoscopic liver resection techniques, anatomic liver resection is one of the most challenging procedures, with disorientation readily occurring during the laparoscopic approach compared with the open approach.1 Thus, navigation is warranted for laparoscopic anatomic liver resection. Recent research has remarkably established intraoperative fluorescence imaging techniques using indocyanine green fluorescence (ICG) in the field of liver surgery.2 - 4 This report describes real-time navigation for anatomic liver resection using the novel ICG system, PINPOINT (Stryker, Kalamazoo, MI)., Methods: The target Glissonian pedicle was identified and temporally clamped after confirmation of blood supply to the preserved adjacent segment using ultrasonography. Next, 1.5 mg of ICG was intravenously administered using the negative counterstaining method. After 3 min of administration, the ICG-stained area could be readily recognized. Parenchymal transection was subsequently initiated along the interface between the ICG-positive and ICG-negative areas using the Pringle maneuver., Results: Using PINPOINT, laparoscopic anatomic liver resection was performed for 16 patients. The extent of liver resection comprised two left hepatectomies, three right-anterior sectionectomies, three right-anterior sectionectomies, and eight segmentectomies. The identification rate of clear demarcations in the ICG images was 100%. The intraoperative blood loss was 226 mL, and the operative time was 305 min. Only one patient encountered the major postoperative complication of ascites, and all the patients attained R0 resection., Conclusions: Because the images provided by the ICG system are clearer than conventional ICG images, it could facilitate real-time navigation for laparoscopic anatomic liver resection.

Purposes: The relationship between the results of bacterial drainage fluid cultures in the early postoperative period after liver resection and the development of surgical site infections (SSIs) is unclear. We evaluated the diagnostic value of bacterial cultures of drainage fluid obtained on postoperative day (POD) 1 after liver resection., Methods: The cases of all consecutive patients who underwent elective liver resection from January 2014 to December 2016 were analyzed. The association between a positive culture result and the development of SSIs was analyzed., Results: A total of 195 consecutive patients were studied. Positive drainage fluid cultures were obtained in 6 patients (3.1%). A multivariate analysis revealed that a positive drainage fluid culture was an independent risk factor for SSIs (odds ratio: 8.04, P = 0.035), and combined resection of the gastrointestinal tract was a risk factor for a positive drainage fluid culture (P = 0.006). Among the patients who did not undergo procedures involving the gastrointestinal tract, there was no association between drainage fluid culture positivity and SSIs., Conclusions: The detection of positive culture results for drainage fluid collected on POD 1 after liver resection was associated with SSIs. However, among patients who did not undergo procedures involving the gastrointestinal tract, it was not a predictor of SSIs.

Background: There is no clear evidence that preoperative chemotherapy for resectable colorectal liver metastasis (CRLM) is superior to up-front surgery (UFS). The aim of this study was to identify the risk factors associated with poor prognosis after UFS for CRLM., Methods: Data about consecutive patients with CRLM who underwent liver resection at Nara Medical University Hospital between January 2000 and December 2015 were retrieved from a prospective database. Recurrence that developed within 2 years after liver resection and could not be surgically resected was defined as unresectable recurrence (UR). Preoperative risk factors associated with UR after UFS were analyzed. Among the patients with the identified risk factors, the patients who were treated with UFS were compared with those who received preoperative chemotherapy via propensity score-matching analysis., Results: There were 167 patients treated with UFS, and 71 of them developed UR (the UR group). The overall survival (OS) rate of the UR group was significantly worse than that of the non-UR group (5-year survival rate: 3.8 vs. 66.8%, p < 0.001). Multivariate analysis identified a primary colorectal cancer N factor of N2-3 as a risk factor for UR (hazard ratio 2.72, p = 0.004). Propensity score-matching analysis demonstrated that among patients with N2-3 primary colorectal cancer the post-initial treatment OS of the patients treated with UFS was significantly worse than that of the patients who received preoperative chemotherapy (5-year survival rate: 11.1 vs. 30.0%, p = 0.046)., Conclusions: Patients with CRLM with a primary colorectal cancer N factor of N2-3 should be considered for preoperative chemotherapy.

Background: It is unclear whether anatomic resection achieves better outcomes than nonanatomic resection in patients with hepatocellular carcinoma. This study aimed to compare the outcomes of anatomic resection and nonanatomic resection for hepatocellular carcinoma located on the liver surface via one-to-one propensity score-matching analysis., Methods: Data from all consecutive patients who underwent liver resection for primary solitary hepatocellular carcinoma at Nara Medical University Hospital, Japan, January 2007- December 2015 were retrieved. Superficial hepatocellular carcinomas were defined as hepatocellular carcinoma that extended to a depth of < 3 cm from the liver surface and measured < 5 cm in diameter. The prognoses of the patients with superficial hepatocellular carcinoma who underwent anatomic resection and nonanatomic resection were compared., Results: In this study 23 patients with superficial hepatocellular carcinoma underwent anatomic resection and 70 patients who underwent nonanatomic resection. The recurrence-free survival rate of the patients who underwent anatomic resection was better than that of the patients who underwent nonanatomic resection (P = .006), while no such difference was observed for nonsuperficial hepatocellular carcinoma. After the propensity score-matching procedure, the resected liver volume and operation time were the only background or clinical characteristics to exhibit significant differences between the anatomic resection (n = 20) and nonanatomic resection groups (n = 20). The recurrence-free survivial rate of the patients who underwent anatomic resection was significantly than that of the patients that underwent nonanatomic resections (P = .030), but overall survival did not differ significantly between the groups (P = .182)., Conclusion: Anatomic resection decreases the risk of tumor recurrence and improves recurrence-free survival compared with nonanatomic resection in patients with superficial hepatocellular carcinoma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Postoperative ascites is a common complication after liver resection. This study aimed to identify the risk factors for ascites in patients after liver resection and the relationship between postoperative ascites and other complications., Methods: We retrospectively analyzed data that were obtained from 266 patients who underwent liver resection for treating hepatocellular carcinoma between 2008 and 2015. Postoperative ascites was defined as a daily ascitic fluid drainage exceeding 500 mL on postoperative day 3 or later. The participants were categorized and analyzed with respect to the presence or absence of postoperative ascites., Results: Overall, 17 (6.4%) patients developed postoperative ascites. A multivariate analysis identified that three significant factors-serum albumin, platelet count, and operation duration-were associated with the development of postoperative ascites. Sixteen (94.1%) of the 17 patients with postoperative ascites experienced other associated complications. The patients with ascites had more pleural effusion (70.6 vs. 17.7%, P < 0.001) than the patients without ascites. Postoperative morbidity, except for pleural effusion, was similar between the groups. The postoperative hospital stay duration was significantly longer in patients with ascites than in those without ascites., Conclusions: Postoperative ascites frequently occurred in patients with decreased liver functional reserve. Moreover, the presence of ascites was associated with significantly increased pleural effusion rates, and postoperative hospital stay duration was significantly prolonged.

Background: Prophylactic drainage after liver resection remains a common practice amongst hepatic surgeons. However, there is little information about the optimal timing of drain removal., Methods: From April 2008 to December 2012 (conventional group), the drains were removed based on the treating surgeon's view. From January 2013 to April 2016 (ERP group), the drains were removed on POD 3 if the bile concentration of the drain discharge was less than three times the serum bilirubin on POD 3, and the amount of drain discharge was <500 ml on POD 3. The postoperative outcomes of the two groups were compared using one-to-one propensity score-matching analysis., Results: One hundred nine patients were extracted from ERP group (n = 226) and conventional group (n = 246). The time to drain removal was significantly shorter in the ERP group than in the conventional group (3 days vs. 5 days, P < 0.001). The frequency of delayed bile leakage or the appearance of symptomatic abdominal fluid collection after drain removal did not differ between the two groups (3% vs. 4%, P = 0.791)., Conclusion: Drain removal on POD 3 based on the volume and bile concentration is safe., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Few studies have reported the long-term outcomes of surgical resected intraductal papillary neoplasm of the bile duct (IPNB). Here, we describe the long-term observation and treatment of a case of widespread IPNB., Presentation of Case: A 57-year-old male was referred to our hospital due to jaundice and dilation of the intrahepatic bile duct. Computed tomography showed dilation and irregularities of the right intrahepatic and extrahepatic bile ducts together with a 3cm nodule in the common hepatic duct. Peroral cholangioscopy revealed mucinous discharge from the ampulla of Vater, which resulted in a diagnosis of IPNB. A biopsy of the nodule and the bile duct revealed papillary adenoma in all of them. Right hepatectomy, caudate lobectomy, extrahepatic bile duct resection, and left hepaticojejunostomy were performed. The nodule was histologically diagnosed as papillary carcinoma in situ, and R0 resection was performed. However, mucus production from the papillary adenoma in the B3 and B4 was observed. We carefully managed the patient's biliary tract by inserting a biliary drainage tube into the segment 2, and he has survived for more than 7 years since the initial treatment., Discussion: Mucus might be produced after the surgical resection of IPNB even if s surgical margin was benign. Five-year survival rate of benign IPNB was reported from 85% to 100%. That might be caused by difference of the postoperative management of the biliary tract., Conclusions: Careful management of the biliary tract should be performed after surgical resection of IPNB., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There are a few studies that have evaluated postoperative analgesia. The aim of this study was to evaluate the safety of administering celecoxib to manage postoperative pain after liver surgery., Methods: The cases of patients who underwent liver resection at Nara Medical University from April 2008 to December 2015 were retrospectively analyzed. From January 2013 to December 2015, celecoxib was routinely administered (600 mg/day on postoperative day (POD) 2 and 400 mg/day from POD 3-7), whereas celecoxib was not administered from April 2008 to December 2012. The patients' baseline characteristics, the operative procedures, and postoperative complications were analyzed., Results: In total, 207 patients were administered celecoxib (celecoxib group), whereas 246 were not (non-celecoxib group). The preoperative serum total bilirubin and creatinine levels and indocyanine green retention rate at 15 min values of the 2 groups were similar. Similar incidences of overall and major complications (Clavien-Dindo classification ≥grade IIIa) were seen in both groups (33.8 vs. 36.2%, p = 0.601 and 12.1 vs. 12.6%, p = 0.866, respectively). No significant differences in the incidences of gastrointestinal bleeding, acute renal failure, or portal vein thrombosis were observed between the groups., Conclusions: The use of celecoxib for postoperative analgesia in the early period after liver resection is safe., (© 2016 S. Karger AG, Basel.)

Background and Objectives: The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for ≥4 CRLM., Methods: Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with ≥4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan., Results: There were 50 and 144 patients with ≥4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of ≥20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of ≥100 U/ml (P = 0.018), and a primary colorectal cancer N factor of ≥N2 (P = 0.023)., Conclusions: The prognosis of patients with ≥4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959-965. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The prognosis of hepatocellular carcinoma(HCC)with main portal vein(MPV)and/or the inferior vena cava(IVC)tumor thrombi is dismal. The management of HCC with severe tumor thrombus is complicated. In this study, we report a case of HCC with tumor thrombi in the MPV and IVC that was successfullytreated via liver resection and perioperative hepatic arterial infusion chemotherapy(HAI). A 68-year-old man was referred to our institution to treat huge HCC lesion in the right lobe of the liver. Abdominal computed tomography(CT)revealed a tumor(12 cm in diameter)in the right hepatic lobe and tumor thrombi in the MPV and IVC. The patient was initiallytreated with HAI(cisplatin 100mg/body). After 3 courses of HAI, the tumor was dramaticallyreduced in size, and the thrombus in the IVC had disappeared; however, the thrombus in the MPV remained. Therefore, we performed right hepatectomy, wedge resection of the IVC, combined resection of the MPV, and portal vein reconstruction. The histopathological findings of the resected specimen revealed that viable cancer cells were observed onlyin an 8×8mm lesion. Subsequently, HAI was performed as adjuvant therapy for 3 courses. The patient died of other causes 2 years 3 months after surgery. There was no sign of recurrence at the time of death. This case suggested that perioperative HAI and liver resection mayrepresent an effective treatment strategyfor HCC with severe tumor thrombus.

The patient was a 73-year-old man, diagnosed with advanced huge hepatocellular carcinoma with a tumor thrombus extending into the inferior vena cava and extrahepatic metastases. Radiation therapy(50 Gy)was applied for the bone metastases, primary tumor, and tumor thrombus, and the patient received a cisplatin transcatheter arterial infusion(100mg/ body, 5 courses). Sorafenib was administered orally once the local lesion was under control. The tumor showed a partial response according to the RECIST criteria, but the tumor thrombus in the inferior vena cava almost disappeared. The presence of a tumor thrombus in the inferior vena cava must be regarded as an oncologic emergency. Acisplatin transcatheter arterial infusion and radiation therapy may be treatment options for unresectable cases.