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Aim: Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway., Methods: Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl 4 )-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity., Results: The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence., Conclusion: Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Background: The number of older patients with cancer has increased, and colorectal cancer is expected to be affected by this trend. This study aimed to compare prognostic factors, including nutritional and inflammation-based indices, between patients aged ≥ 70 and < 70 years following curative resection of stage I-III colorectal cancer., Patients and Methods: This study included 560 patients with stage I-III colorectal cancer who underwent curative resection between May 2010 and June 2018. A retrospective analysis was performed to identify prognosis-associated variables in patients aged ≥ 70 and < 70 years., Results: Preoperative low body mass index, high C-reactive protein/albumin ratio, and comorbidities were mainly associated with poor prognosis in patients aged ≥ 70 years. Tumor factors were associated with a poor prognosis in patients aged < 70 years. The C-reactive protein/albumin ratio was independently associated with poor overall survival and recurrence-free survival in those aged ≥ 70 years. The time-dependent area under the curve for the C-reactive protein/albumin ratio was superior to those of other nutritional and inflammation-based indices in most postoperative observation periods in patients aged ≥ 70 years., Conclusions: Tumor factors were associated with a poor prognosis in patients aged < 70 years. In addition to lymph node metastasis, preoperative statuses were associated with poor prognosis in patients aged ≥ 70 years. Specifically, the preoperative C-reactive protein/albumin ratio was independently associated with long-term prognosis in patients aged ≥ 70 years with stage I-III colorectal cancer after curative resection., (© 2024. The Author(s).)

Introduction: Hepatocellular carcinoma (HCC) is a major global health challenge, being the fifth most prevalent neoplasm and the third leading cause of cancer-related deaths worldwide. Liver transplantation offers a potentially curative approach for HCC, yet the risk of recurrence posttransplantation remains a significant concern. This study investigates the influence of a liver immune status index (LISI) on the prognosis of patients undergoing living-donor liver transplantation for HCC., Methods: In a single-center study spanning from 2001 to 2020, 113 patients undergoing living-donor liver transplantation for HCC were analyzed. LISI was calculated for each donor liver using body mass index, serum albumin levels, and the fibrosis-4 index. This study assessed the impact of donor LISI on short-term recurrence rates and survival, with special attention to its correlation with the antitumor activity of natural killer (NK) cells in the liver., Results: The patients were divided into two grades (high donor LISI, >-1.23 [n = 43]; and low donor LISI, ≤-1.23 [n = 70]). After propensity matching to adjust the background of recipient factors, the survival rates at 1 and 3 years were 92.6% and 88.9% and 81.5% and 70.4% in the low and high donor LISI groups, respectively (p = 0.11). The 1- and 3-year recurrence-free survival were 88.9% and 85.2% and 74.1% and 55.1% in the low and high donor LISI groups, respectively (p = 0.02)., Conclusions: This study underscores the potential of an LISI as a noninvasive biomarker for assessing liver NK cell antitumor capacity, with implications for living-donor liver transplantation for HCC. Donor LISI emerges as a significant predictor of early recurrence risk following living-donor liver transplantation for HCC, highlighting the role of the liver antitumor activity of liver NK cells in managing liver malignancies., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: This study aimed to assess the risk factors for components of metabolic syndrome, such as diabetes mellitus, hypertension, and dyslipidemia, more than a year after liver transplantation., Methods: This study included 164 patients with liver failure secondary to acute and chronic liver disease or hepatocellular carcinoma who underwent liver transplantation between 2000 and 2019. Univariate and multivariate analyses were performed to identify the risk factors associated with metabolic syndrome components after liver transplantation., Results: The median follow-up period was 10.5 years. Of the 164 patients who underwent liver transplantation, 144 (87.8%) developed components of metabolic syndrome after liver transplantation. The most common cause of liver failure was hepatitis C virus infection (34.1%). The incidence of hepatocellular carcinoma was 36.0%. In univariate analysis, preoperative diabetes mellitus was a significantly more common component of metabolic syndrome than the others. In multivariate analysis, preoperative abdominal aortic calcification was a risk factor for the new onset of all components of metabolic syndrome after liver transplantation, despite the varying degree of calcification at risk of development (odds ratio for diabetes mellitus = 3.487, P = .0069; odds ratio for hypertension = 2.914, P = .0471; odds ratio for dyslipidemia = 3.553, P = .0030)., Conclusions: Preoperative abdominal aortic calcification was significantly associated with the development of each metabolic syndrome component after liver transplantation., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV), the most common opportunistic infection of kidney transplantation (KT), is preventable by prophylactic and preemptive antiviral drugs in CMV-immunoglobulin (Ig)G-positive donors. Our preemptive therapy optimized immunosuppressive doses based on mixed lymphocyte response (MLR) results, regardless of preoperative CMV-IgG serostatus pairing. This study used the MLR to compare the anti-donor T-cell responses between CMV antigenemia-positive and -negative cases., Methods: One hundred patients underwent KT using a cyclosporine (CsA)-based immunosuppressive regimen at Hiroshima University Hospital. CMV antigenemia-positive cells were defined as 4/50,000 CMVpp65-positive cells. T-cell responses to allo-antigens were measured using MLR assays to evaluate patients' anti-donor immune reactivity. After analyzing the proliferation of CD4 + and CD8 + T-cell subsets, the stimulation indices of CD4 + or CD8 + T cells were quantified. The study used no prisoners, and the participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul., Results: Forty-three patients tested positive for CMV antigenemia within 3 months after KT. No significant differences were found between the CMV antigenemia-positive and -negative groups in the stimulation indices for CD4 + and CD8 + T-cell responses to anti-donor stimulation. However, T-cell responses to third-party stimuli during the postoperative month 1 were significantly less in the CMV antigenemia-positive than -negative group., Conclusion: Anti-donor T-cell responses are not necessarily attenuated during CMV infection in KT recipients. In CMV-infected KT recipients, caution should be exercised against inadvertent dose reduction of immunosuppressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Abdominal aortic calcification (AAC) is associated with cardiovascular-related mortality, along with an elevated risk of coronary, cerebrovascular, and cardiovascular events. Notably, AAC is strongly associated with poor overall and recurrence free survival posthepatectomy for hepatocellular carcinoma. Despite the acknowledged significance of atherosclerosis in systemic inflammation, its response to ischemia/reperfusion injury (IRI) remains poorly elucidated. In this study, we aimed to clarify the impact of atherosclerosis on the liver immune system using a warm IRI mouse model., Methods: Injury was induced in an atherosclerotic mouse model (ApoE -/- ) or C57BL/6J wild-type (WT) mice through 70% clamping for 1 hour and analyzed after 6 hours of reperfusion., Results: Elevated serum levels of aspartate and alanine aminotransferase, along with histological assessment, indicated considerable damage in the livers of ApoE -/- mice than that in WT mice. This indicates a substantial contribution of atherosclerosis to IRI. Furthermore, T and natural killer (NK) cells in ApoE -/- mouse livers displayed a more inflammatory phenotype than those in WT mouse livers. Reverse transcription-polymerase chain reaction analysis revealed a significant upregulation of interleukin (IL)-15 and its transcriptional regulator, interferon regulatory factor-1 (IRF-1) in ApoE -/- mouse livers compared with that in WT mouse livers., Conclusions: These findings suggest that in an atherosclerotic mouse model, atherosclerosis can mirror intrahepatic immunity, particularly activating liver NK and T cells through IL-15 production, thereby exacerbating hepatic damage. The upregulation of IL-15 expression is associated with IRF-1 overexpression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic indicator in various malignancies; however, the impact of postoperative NLR on living donor liver transplant (LDLT) recipients is unknown. Immunotherapy with donor liver-derived activated natural killer (NK) cells may improve postoperative NLR by coactivating immune cells or suppressing activated neutrophils. This study aims to clarify the clinical significance of postoperative NLR in recipients after LDLT with HCC and assess whether immunotherapy improves postoperative NLR., Methods: We conducted a retrospective study of LDLT recipients between 2001 and 2022 to evaluate the clinical significance of postoperative NLR. Furthermore, the correlation between postoperative NLR and the activation marker of infused NK cells was also evaluated. The postoperative NLR was examined 4 weeks after LDLT., Results: The postoperative high NLR group (N = 78) had preoperative lower NLR and higher model for end-stage liver disease and a higher rate of postoperative infection within 30 days after LDLT than the postoperative low NLR group (N = 41). Postoperative high NLR (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.01-6.79; P = .047) and nontreatment of immunotherapy (HR, 3.10; 95% CI, 1.33-7.22; P < .01) were independent risk factors for poor overall survival in multivariate analysis. Furthermore, the activation marker of infused NK cells is inversely correlated with decreased postoperative NLR., Conclusions: The higher level of postoperative NLR was independently associated with poor prognosis in patients after LDLT with HCC. Immunotherapy using activated NK cells may improve postoperative NLR and long-term prognosis., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Natural killer (NK) cells are involved in innate immunity and have been reported to play an important role in hepatocellular carcinoma recurrence and post-liver transplantation (LT) infection. However, the relationship between donor age and liver-resident NK cell activity remains to be elucidated., Methods: We successfully performed NK cell immunotherapy in 19 living donor LT recipients to prevent post-LT bloodstream infections. Liver mononuclear cells (LMNCs) were collected from the liver graft perfusate and stimulated with interleukin 2 for 3 days. Liver-resident NK cells were analyzed using flow cytometry and a chromium release assay before and after cell culture., Results: The median donor age was 44 years (range, 24-64 years). The graft weight was 492 g (range, 338-642 g), and the median number of LMNCs was 584 million cells (range, 240-1472 million cells). The proportion of NK cells before and after culture was 22% and 33%, respectively. A significant correlation was found between graft weight and the number of LMNCs. However, no correlation was found between donor age and the number or percentage of NK cells in the liver. Moreover, donor age showed a significant inverse correlation with NKp46 and NKp44 expression before culture and with NKp44, tumor necrosis factor-related apoptosis-inducing ligand, and CD69 expression after culture., Conclusion: A significant inverse correlation was observed between donor age and NK cell activity in the liver. This information may be useful for cell therapy during LT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have seemed to influence in the work in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/aim: The aim of the study was to analyze the association between abdominal aortic calcification (AAC) and patient prognosis following resection of colorectal liver metastases (CRLM). AAC potentially reflects intrahepatic immunity and is involved in tumor development and progression. However, the clinical effects of AAC on colorectal cancer (CRC) prognosis after curative-intent liver resection for CRLM remain unclear., Patients and Methods: We evaluated the effect of AAC on the clinical prognosis and metastatic patterns in 99 patients who underwent hepatectomy for CRLM between 2010 and 2019., Results: The high-AAC group had significantly worse overall survival (OS) and remnant liver recurrence rate (RR) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In multivariate Cox regression analyses, high AAC volume was an independent risk factor for poor OS and liver RR, but not poor lung RR. The expression of tumor necrosis factor-related apoptosis-inducing ligand, known as an anti-tumor marker, in liver natural killer (NK) cells was lower in the high-AAC group than in the low-AAC group., Conclusion: High AAC volume showed a strong relationship with remnant liver RR after curative resection of CRLM. High AAC volume may be responsible for the suppression of anti-tumor activity of liver NK cells, which results in an increased risk of liver recurrence and poor prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Adjuvant chemotherapy is recommended following colorectal cancer resection based on risk of recurrence. In older patients, treatment decisions should consider recurrence rates and tolerability, as well as functional prognosis, residual disease, and social factors. This study aims to investigate factors, including social background, influencing implementation of postoperative adjuvant chemotherapy in older patients undergoing curative resection for colorectal cancer., Methods: This multi-institutional prospective cohort study included 15 institutions belonging to the Hiroshima Surgical study group for Clinical Oncology. We analyzed 159 older patients aged ≥ 80 years, who underwent curative resection for stage III colorectal cancer between December 2013 and June 2018, as sub-analysis of the HiSCO-04 study., Results: In total, 62 (39.0%) patients underwent postoperative adjuvant chemotherapy. Four factors were significantly associated with its implementation: performance status < 2, Charlson Comorbidity Index < 2, prognostic nutritional index ≥ 40, and presence of a spouse or siblings as lifestyle supporters. No significant difference was found in the backgrounds between complete and incomplete postoperative adjuvant chemotherapy patients., Conclusion: Performance status, Charlson Comorbidity Index, nutritional status, and presence of a spouse or siblings as lifestyle supporters are possible factors influencing the implementation of postoperative adjuvant chemotherapy in older patients. To select appropriate treatment options, including postoperative adjuvant chemotherapy, it is essential to consider physical condition and comorbidities of older patients, thoroughly explain the situation to their families, and establish a support system to enhance understanding of the available treatment options., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Liver-resident natural killer (lr-NK) cells are distinct from conventional NK cells and exhibit higher cytotoxicity against hepatoma via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). However, the mechanism by which partial hepatectomy (PH) significantly suppresses TRAIL expression in lr-NK cells remains unclear., Methods: This study aimed to investigate the PH influence on the function and characteristics of liver-resident NK (lr-NK) cells using a PH mouse model., Results: Here, we report that PH alters the differentiation pattern of NK cells in the liver, and an aryl hydrocarbon receptor (AhR) molecule is involved in these changes. Treatment with the AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ) inhibited the maturation of NK cells. FICZ increased the immature subtype proportion of NK cells with high TRAIL activity and decreased the mature subtype of NK cells with low TRAIL activity. Consequently, FICZ increased the expression of TRAIL and cytotoxic activity of NK cells in the liver, and this effect was confirmed even after hepatectomy. The participation of AhR promoted FoxO1 expression in the mTOR signaling pathway involved in the maturation of NK cells, resulting in TRAIL expression., Conclusion: Our findings provide direct in-vivo evidence that partial hepatectomy affects lrNK cell activity through NK cell differentiation in the liver. Perioperative therapies using an AhR agonist to improve NK cell function may reduce the recurrence of hepatocellular carcinoma after hepatectomy., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: The anti-tumor effects of natural killer (NK) cells vary among individuals. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressed on liver NK cells is a marker of anti-tumor cytotoxicity against hepatocellular carcinoma (HCC) in immune cell therapy. This study aimed to develop a liver immune status index (LISI) that predicts low TRAIL expression and validates its ability to predict recurrence after initial hepatectomy for primary HCC., Methods: A functional analysis of liver NK cells co-cultured with interleukin-2 for 3 days was performed of 40 liver transplant donors. The LISI, which predicted low TRAIL expression (25% quartile: <33%) in liver NK cells, was calculated using multiple logistic regression analysis. Next, 586 initial hepatectomy cases were analyzed based on the LISI., Results: Our model was based on the Fibrosis-4 index +0.1 (odds ratio [OR], 1.33), body mass index (OR, 0.61), and albumin levels +0.1 (OR, 0.54). The area under the receiver operating characteristic curve (AUC) of the LISI for low TRAIL expression was 0.89. Stratification of the recurrence rates (RR) revealed that LISI was an independent predictive factor of RR (moderate risk: hazard ratio, 1.44; high risk: hazard ratio, 3.02). The AUC was similar for the LISI, albumin-indocyanine green evaluation grade, albumin-bilirubin score, and geriatric nutritional risk index for predicting RR. Among the vascular invasion cases, the LISI was more useful than the other indexes., Conclusion: Our model facilitates the prediction of RR in high-risk patients by providing LISI to predict the anti-tumor effects of NK cells., Competing Interests: Hideki Ohdan is an editorial board member., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Purpose: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection., Methods: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020., Results: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection., Conclusions: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In kidney transplantation (KT), efforts to minimize rewarming and optimize anastomosis time during vascular anastomosis improve graft outcomes. We recently reported the safety and efficacy of a pouch-type thermal barrier bag (TBB) made of elastomer gel to reduce second-warm ischemic injury during vascular anastomosis. We aimed to examine the usefulness of the TBB in prolonged vascular anastomosis in KT performed by young transplant fellows., Methods: Young transplant fellows performed KT under the supervision of certified transplant surgeons. The kidney graft was placed inside the TBB with an outlet for vessels and preserved during vascular anastomosis. A non-contact infrared thermometer measured the graft surface temperature before and after vascular anastomosis. After completion of the anastomosis, the TBB was manually slid out of the transplanted kidney and removed before graft reperfusion. Clinical data, including patient characteristics and perioperative variables, were collected. The primary endpoint was the median graft surface temperature at the end of the anastomosis., Results: Ten living-donor kidney transplant recipients with a median age of 56.5 years (range, 40-69 years) underwent KT procedures performed by young transplant fellows. The median anastomosis time was 53 (43-67) min. At the end of anastomosis, the median graft surface temperature was 17.7°C (16.3-18.3°C); no serious adverse events or delayed graft function were observed., Conclusion: The TBB can keep transplanted kidneys at a low temperature even with prolonged vascular anastomosis time, thus contributing to the functional preservation of transplanted kidneys and stable transplant outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is critical for natural killer (NK) cell-mediated anti-tumor and anti-microbe killing. The TRAIL expression on the donor's liver NK cells from the liver perfusate after interleukin-2 stimulation varies between individuals and is unpredictable. This study aimed to clarify the risk factors for low TRAIL expression by analyzing perioperative donor characteristics., Methods: This retrospective study of living donor liver transplant (LDLT) donors between 2006 and 2022 was performed to analyze low TRAIL expression risk factors. Seventy-five donors who had undergone hepatectomy for LDLT were divided into 2 groups, low and high TRAIL, according to their TRAIL expression on liver NK cells, using median values., Results: The low TRAIL group (N = 38) was older and had lower nutrition and a higher low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, related to arteriosclerosis, than the high TRAIL group (N = 37). In multivariate analysis, the geriatric nutritional risk index (GNRI) (odds ratio, 0.86; 95% CI, 0.76-0.94; P < .001) and LDL/HDL cholesterol ratio (odds ratio, 2.32; 95% CI, 1.10-4.86; P = .005) were independent predictive factors for low TRAIL expression on liver NK cells. Furthermore, the TRAIL expression of liver NK cells decreased in donors who already had atherosclerosis and in donors at risk of potentially developing atherosclerosis., Conclusions: The TRAIL expression on liver NK cells in donors had a strong relationship with atherosclerosis and GNRI. Atherosclerosis can reflect the TRAIL expression on liver NK cells., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The rate of postoperative morbidity, including infectious complications, is still high after major hepatobiliary pancreatic (HBP) surgery. Although surgery-related disseminated intravascular coagulation (DIC) occurs in some cases, its significance has not been elucidated in HBP surgery. This study aimed to evaluate the influence of surgery-related DIC on the complication severity after HBP surgery., Methods: We analyzed the records of 100 patients with hepatectomy in two or more segments, hepatectomy with biliary tract reconstruction, and pancreaticoduodenectomy. The baseline characteristics and complications were compared between patients with and without surgery-related DIC on postoperative day 1 (POD1) after HBP surgery between 2010 and 2018. Complication severity was assessed using the Comprehensive Complication Index (CCI)., Results: The DIC group (surgery-related DIC on POD1) had predictive factors, such as larger bleeding volume and higher liver enzyme levels. The DIC group exhibited significantly elevated rates of surgical site infection, sepsis, prolonged intensive care unit stay, more frequent blood transfusions, and higher CCI. Furthermore, compared with and without adjustment of DIC, odds ratio (OR) of AST level and operation time for  the risk of high CCI decreased (OR of AST level: 1.25 to 1.19 and OR of operation time: 1.30 to 1.23) and the significant differences had vanished., Conclusions: Surgery-related DIC on POD1 could be a partial mediator between AST level, operation time and higher CCI. The prevention or proper management of surgery-related DIC on POD1 can be an important target to reduce the severity of postoperative complications., (© 2023. The Author(s).)

Introduction: There are various methods for appendiceal stump dissection, but the necessity for stump invagination remains unclear. This study aimed to assess the efficacy of appendiceal stump invagination in patients with acute appendicitis after laparoscopic appendectomy (LA)., Methods: We enrolled 327 patients with acute appendicitis who underwent LA between 2012 and 2020. Perioperative variables and surgical outcomes were analyzed between the invagination of the appendiceal stump and noninvagination groups. Propensity score-matched analysis (PSM) was performed., Results: More patients experienced severe inflammation and severe intra-abdominal contamination in the noninvagination group than in the invagination group. Patients in the noninvagination group had an older age, higher body mass index, and poorer American Society of Anesthesiologists physical status than the invagination group. Severe inflammation in the noninvagination group was associated with longer hospital stays and poorer postoperative complications than in the invagination group. PSM analysis was performed to minimize bias in the two groups. After PSM analysis, there were no significant differences in surgical site infection, postoperative intra-abdominal abscess, Clavien-Dindo class ≥IIIa, or postoperative stay between the two groups. During the follow-up period, the postoperative adhesive ileus was not significantly different between the invagination and noninvagination groups., Conclusion: Invagination of the appendiceal stump during LA is not necessary to prevent short- and long-term complications. Even in cases dissected using a laparoscopic endostapler, the appendiceal stump per se is not related to postoperative adhesive ileus., (© 2022 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Purpose: Abdominal aortic calcification (AAC) is a well-known risk marker for cardiovascular disease. However, its clinical effect on patients who underwent radical surgery for colorectal cancer (CRC) stages II-III is unclear. This study aimed to analyze the associations between AAC and prognosis of patients with stage II-III CRC., Methods: To evaluate the effect of AAC on clinical outcomes, prognosis, and metastatic patterns of CRC, we analyzed 362 patients who underwent radical surgery for stage II-III CRC between 2010 and 2018., Results: The high AAC group had significantly worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In the multivariate Cox regression analyses, a high AAC was an independent risk factor for poor OS (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.23-4.59; p = 0.01), poor CSS (HR, 5.22; 95% CI, 1.74-15.6; p < 0.01), and poor RFS (HR, 1.83; 95% CI, 1.19-2.83; p < 0.01). A high AAC was not associated with a risk of lung metastasis or local or peritoneal recurrence, but a risk for liver metastasis of CRC., Conclusion: A high AAC showed a strong relationship with poor OS, CSS, and RFS after curative resection for stage II-III CRC. A high AAC was also associated with a risk for liver metastasis, which may worsen the prognosis in stage II-III CRC. AAC could be a new clinical tool for predicting the prognosis for patients in stage II-III CRC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: The rate of postoperative morbidity after major hepatobiliary pancreatic (HBP) surgery is estimated to be high. We hypothesized that the frailty and insufficient blood supply of organs caused by arteriosclerosis may lead to increased severity of postoperative complications. The aim of this study was to clarify the relationship between abdominal aortic calcification (AAC) and severity of major HBP surgery postoperative complications., Patients and Methods: A total of 322 major HBP surgeries were performed in Hiroshima University Hospital, Japan from January 2010 to March 2018. The records of 214 patients were retrospectively analyzed to include those with hepatectomy in two or more segments. These included donor hepatectomy, hepatectomy with biliary tract reconstruction, and pancreaticoduodenectomy. We compared the baseline AAC levels (cut-off; 1,000 mm 3 ) with their corresponding levels after HBP surgery complications developed. The complication severity was assessed using the Comprehensive Complication Index (CCI)., Results: The high-AAC (N=71) group had significantly increased incidence rates of surgical site infections and a higher CCI, even after propensity matching. Multivariate analysis revealed that a higher AAC was an independent risk factor of severe postoperative complications (CCI ≥40) (OR=10.21, p<0.01)., Conclusion: An increased AAC has a corresponding increase in postoperative complication severity after major HBP surgery. Careful anastomosis and infection control are required to prevent the progression of severe postoperative complications among high-AAC patients., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The occurrence of schwannomas in the hepatoduodenal ligament is rare, and its preoperative accurate diagnosis is difficult. Only few cases have been treated with laparoscopic surgery., Case Presentation: A 54-year-old man visited our hospital following abnormal abdominal computed tomography findings. He had no complaints, and his laboratory investigations were normal. Abdominal contrast-enhanced computed tomography revealed a tumor with enhancement at the margin of the hepatoduodenal ligament. The abdominal magnetic resonance imaging findings of the tumor showed hypointensity on the T1-weighted images and mixed hypointensity and hyperintensity on the T2-weighted fat-suppression images. Positron emission tomography showed localized accumulation of fludeoxyglucose only in the hepatoduodenal ligament tumor. The patient underwent laparoscopic tumor resection for accurate diagnosis. Histopathologically, the tumor was mainly composed of spindle cells, which were strongly positive for S-100 protein on immunohistochemical staining. The patient was discharged without any postoperative complications on day 5., Conclusions: Complete tumor resection is essential for schwannomas to avoid recurrence. Laparoscopic surgery is useful for schwannomas occurring in the hepatoduodenal ligament and can be performed safely by devising an appropriate surgical method., (© 2021. The Author(s).)

Objectives: Anastomotic leakage is associated with severe morbidity, mortality, and functional defects. Its risk factors remain unclear. However, blood perfusion may be a potential major risk factor. It has been reported that the Agatston score is an index for blood flow perfusion evaluation. Therefore, we evaluated the clinical indicators associated with anastomotic leakage, including the Agatston score, in patients who underwent colorectal surgery., Methods: We retrospectively analyzed 147 patients who underwent elective colorectal surgery with the double-staple technique anastomosis for colorectal cancer between April 2015 and March 2020. The primary outcome was the presence or absence of anastomotic leakage. Univariate and multivariate analyses were employed to identify pre- and intraoperative risk factors., Results: Of the 147 patients analyzed, anastomotic leakage occurred in 12 (8.16%). Male gender, history of angina and myocardial infarction, preoperative white blood cell count, the Agatston score, extent of bleeding, operation time, and intraoperative fluid volume were significantly related to a higher incidence of anastomotic leakage in univariate analysis. Multivariate analysis demonstrated that the incidence of anastomotic leakage was high in patients with a high Agatston score., Conclusions: The Agatston score can predict the incidence of anastomotic leakage in patients following colorectal surgery. Thus, perioperative measures to prevent anastomotic leakage are recommended when a high Agatston score is observed. A prospective trial is required to demonstrate, with a high level of evidence, that the Agatston score can be useful as a risk score for anastomotic leakage following colorectal surgery., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2021 by The Japan Society of Coloproctology.)

Background: Submucosal fecalith(s) mimicking submucosal tumors of the gastrointestinal lumen are rare. Moreover, accurate preoperative diagnosis of these entities is exceedingly difficult, and the mechanism(s) of their formation remains unclear., Case Presentation: A 40-year-old woman visited the authors' hospital due to lower abdominal pain and diarrhea. She had previously been treated for endometriosis. Laboratory investigation revealed increased C-reactive protein levels. Abdominal contrast-enhanced computed tomography revealed thickening of the appendix wall and dilation of the small intestine. The patient was diagnosed with paralytic ileus caused by appendicitis, and interval appendectomy was scheduled. She underwent laparoscopic-assisted appendectomy after conservative treatment. Partial cecal resection was selected due to the presence of an elastic mass in the cecum. The final pathological diagnosis was submucosal fecalith, not submucosal tumor. On day 5, the patient was discharged without any postoperative complications., Conclusions: In cases of appendicitis with fecalith(s) that appear as submucosal tumor(s) on colonoscopy, submucosal fecalith mimicking submucosal tumor should be considered in the differential diagnosis.

Introduction: The revised Tokyo guideline 2018 (TG18) recommends early laparoscopic cholecystectomy (LC) in patients with acute cholecystitis (AC) who satisfy the Charlson Comorbidity Index criteria and the ASA Physical Status Classification (ASA-PS). Our study aims to determine the efficacy of the TG18 treatment strategy., Methods: We enrolled 324 patients who had been diagnosed with AC according to the TG18 and who underwent cholecystectomy between 2010 and 2018. Perioperative variables and surgical outcomes were analyzed according to the TG18 treatment strategy and severity grading., Results: The Charlson Comorbidity Index and ASA-PS scores were significantly higher in patients with Grade II and Grade III AC than in those with Grade I AC. In patients with a higher severity grading, LC failed, necessitating blood transfusion and bailout surgery. Among patients treated by the TG18 strategy were a higher proportion with Grade I or II AC; their ASA-PS scores were significantly lower than patients with Grade III AC. Compared to patients not treated by the TG18 strategy, this group demonstrated significant differences in the achievement of LC, bailout surgery, postoperative hospital stays, and 90-day mortality rates. Intraoperative blood loss and blood transfusion were significantly higher in those not treated by the TG18 strategy., Conclusions: Our study shows that the TG18 treatment strategy is well-designed and efficacious. Given the high rate of blood transfusion and conversion surgery in treatment strategies other that TG18, special attention should be paid when selecting the optimal treatment strategy., (© 2020 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to assess the prognostic factors including low skeletal muscle mass index (SMI) and perioperative blood transfusion for patients with hepatocellular carcinoma (HCC) following curative surgery., Methods: This study included 139 patients with HCC who underwent hepatectomy between 2005 and 2016. Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and recurrence-free survival (RFS)., Results: Low SMI was significantly related with poor OS, while blood transfusion had a strong impact on RFS. The male ratio and body mass index in the low SMI group were significantly higher than those in the high SMI group. There were no significant differences in age, virus etiology, laboratory data, liver function, tumor makers, and operative variables between the groups. Tumor factors such as tumor diameter, tumor number, poor differentiation, and intrahepatic metastasis (IM) did not significantly differ between the two groups. Operation time, intraoperative blood loss volume, and recurrence ratio were significantly higher in the blood transfusion group than in the non-transfusion group. IM was associated with poor OS and RFS., Conclusions: Low SMI and blood transfusion were independently related with long-term prognosis in patients with HCC following curative surgery.

Background: Formation of a liver abscess due to gastrointestinal perforation by a foreign body is rare. In addition, there are few case reports on laparoscopic surgical treatment of a liver abscess caused by perforation of the gastrointestinal tract by a foreign body., Case Presentation: A 51-year-old man visited our hospital because of fever and anorexia. There were no physical findings except for fever. He had no comorbidities or surgical history. Laboratory tests showed increased inflammatory marker and liver enzyme levels. Abdominal ultrasonography showed a hypoechoic lesion in the left lobe of the liver. Abdominal contrast-enhanced computed tomography revealed an air-containing abscess in the left side of the liver and a high-density linear object. We diagnosed a liver abscess secondary to stomach perforation by a foreign body. Emergency laparoscopic surgery identified a fish bone in the abscess that formed between the stomach and liver. We succeeded in removing the fish bone laparoscopically. The patient was discharged without any postoperative complications on day 11., Conclusions: A liver abscess secondary to perforation of the gastrointestinal tract by a foreign body usually requires surgical treatment. Foreign body removal is important to prevent recurrence of liver abscess. In cases with the foreign body located at the liver margin, a laparoscopic approach to the abscess is very useful.

A 56-year-old woman with complaints of anal bleeding and pain visited our hospital, and an elastic soft mass was detected in the anal canal on digital examination.Colonoscopy showed a black Isp polypoid lesion with a black pit from the anal canal to the lower rectum(P-Rb).She was diagnosed with malignant melanoma based on colonoscopic biopsy.Tumor marker levels(CEA, CA19-9)were not increased.No distant metastasis was detected on abdominal CT.No direct invasion was detected on MRI of the pelvis.The patient underwent laparoscopic abdominoperineal resection and D2 lymph node dissection. Histopathology showed a malignant melanoma(pT4b, N0, M0, pStageⅡC).The patient received interferon therapy as adjuvant therapy.There is no sign of recurrence 2 years and 1 month after the surgery.Anorectal malignant melanoma is relatively rare, so establishment of therapy by the accumulation of cases is desired.

Introduction: Liver metastasis of an anal squamous cell carcinoma (SCC) with a pseudocyst is uncommon. There are many diseases which form hepatic cystic lesions and sometimes it is difficult to arrive at an accurate diagnosis., Presentation of Case: A 69-year-old woman visited our hospital with complaints of bloody stool and difficult defecation. A palpable mass in the anal canal was found on digital examination. The laboratory tests revealed anemia and raised levels of SCC antigen. On endoscopy a type 2 tumor was identified in the anal canal and biopsy revealed SCC. The patient was diagnosed with advanced anal SCC (cT2N1aM0, cStage IIIA) as a result of the examination and underwent chemoradiotherapy (CRT); unfortunately the tumor persisted after CRT. A salvage abdominoperineal resection with D2 and left lateral lymph node dissection was conducted. Histopathologically, the tumor was diagnosed as poorly differentiated SCC. She was readmitted for fever 3 weeks after surgery, and the abdominal CT showed multiple low density areas with enhancement at the edge of the liver, suggesting abscess or metastasis. The metastatic SCC was revealed by cytology of liver drainage and liver biopsy., Discussion: Anal cancers are sometimes encountered however; a pseudo cystic presentation of a liver metastasis is very rare which makes it difficult to distinguish from other diseases., Conclusion: We present a case of SCC in the anal canal with liver metastasis presenting as a hepatic pseudocyst., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: A spontaneous mesenteric hematoma is rare, and its etiology is unclear. We present a very rare case of spontaneous mesenteric hematoma with a fistula to the transverse colon., Presentation of Case: A 90-year-old male visited our hospital because of lower abdominal pain. The physical examination revealed tenderness in the lower abdomen. The laboratory data revealed anemia and low estimated glomerular filtration rate (eGFR). The abdominal contrast-enhanced computerized tomography (CT) indicated a mass with coexisting low- and high-density areas adjacent to the transverse colon. The mass was diagnosed as a mesenteric hematoma. We selected conservative therapy, because the patient's condition was stable. After 15 days from discharge, he was admitted to the hospital again for the complaint of bloody stool. A fistula with blood flowing out at the splenic flexure was reported on colonoscopy. In the laparoscopic operative findings, the hematoma adhered to the stomach, pancreas and omentum. A hand-assisted laparoscopic transverse colectomy including hematoma in the mesentery was successful. The pathological reports revealed that a spontaneous mesenteric hematoma formed the fistula to the colon. The patient was discharged without any postoperative complication on day 10., Discussion: Generally, laparotomy is often chosen for the treatment of mesenteric hematoma. The laparoscopic approach for mesenteric hematoma is useful under the specific condition that the preoperative patient's condition is stable., Conclusions: This is the first case of a spontaneous mesenteric hematoma with a fistula to the colon resected safely by laparoscopic surgery., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study investigated the optimal timing and usefulness of early cholecystectomy for acute cholecystitis in patients with comorbid acute cholangitis., Materials and Methods: In 2011-2016, 252 patients who underwent early cholecystectomy for acute cholecystitis and 7 who underwent delayed cholecystectomy were enrolled and compared. Patients with comorbid acute cholangitis were then divided into those who underwent urgent cholecystectomy (within 72 h after symptom onset), semi-urgent cholecystectomy (3-14 days after symptom onset), or delayed cholecystectomy (3 months after symptom onset)., Results: There were no significant intergroup differences in postoperative complication rate ( p  = 0.561), operation time ( p  = 0.496), or intraoperative blood loss ( p  = 0.151) between those with and those without acute cholangitis. Postoperative stays were significantly longer in the comorbid acute cholangitis group ( p  = 0.004). In the patients with acute cholangitis, the urgent cholecystectomy, semi-urgent, and delayed cholecystectomy groups had comparable intra- and postoperative outcomes., Conclusion: Early cholecystectomy within 14 days after symptom onset was safely performed for patients with concomitant acute cholecystitis and acute cholangitis after the successful treatment of acute cholangitis.

Background: Gastric carcinosarcoma with severe venous invasion is extremely rare, and to the best of our knowledge, this is the first reported case., Case Presentation: A 79-year-old man visited the Onomichi General Hospital following abnormal upper gastrointestinal series findings. Laboratory data demonstrated no anemia, and the serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were not elevated. Endoscopy identified a Borrmann type III lesion in the cardiac end of the stomach. Abdominal contrast-enhanced computerized tomography (CT) indicated that the lesser curvature of the stomach wall was modestly enhanced with bulky lymph nodes. Pathological biopsy examination identified a group 5, papillary adenocarcinoma. We diagnosed advanced gastric cancer with bulky lymph nodes (cT4aN3M0, cStage IIIC). Following neoadjuvant chemotherapy, the patient underwent open total gastrectomy with D2 lymph node dissection. Histopathologically, the tumor consisted of two components: a tubular adenocarcinoma and a sarcoma. The tumor cells were mainly intravenous and were not detected in the gastric wall stroma; this resulted in a venous invasion. Immunohistochemical analysis revealed that the tumor was positive for vimentin and partly positive for desmin and cytokeratin CAM5.2. We diagnosed a true gastric carcinosarcoma with severe venous invasion. Abdominal CT 2 months after surgery showed a low density area in the liver, suggesting metastasis., Conclusions: Carcinosarcomas with lymph node metastasis are sometimes reported, but progression into the vasculature is very rare. We present a case of carcinosarcoma with unusual progression characteristics.

Several recent reports have described the administration of preoperative chemotherapy for locally advanced rectal cancer. In our hospital, preoperative chemotherapy based on oxaliplatin was administered for locally advanced rectal cancer with a tumor diameter of 5 cm or more and half semicircularity or more, and curative resection with laparoscopic surgery was performed after tumor shrinkage. We have experienced 25 cases that underwent preoperative chemotherapy for local advanced rectal cancer in our hospital from May 2012 to April 2016. No tumor increased in size during preoperative chemotherapy and there were no cases where R0 resection was impossible. In addition, no distant metastasis during chemotherapy was observed. Postoperative complications were observed in 3 cases(12%), and anastomotic leakage was observed in 1 case (4%), but conservative treatment was possible. Multidisciplinary treatment of preoperative chemotherapy and surgery should be considered as a therapeutic strategy for locally advanced rectal cancer, mainly in medical institutions without radiation treatment facilities.

Introduction: Gallbladder torsion is mainly associated with a floating gallbladder. From an anatomical perspective, laparoscopic cholecystectomy is a more optimal treatment than open cholecystectomy., Presentation of Case: An 84-year-old woman visited the Onomichi General Hospital because of progressive pain in the right upper quadrant of her abdomen. Physical examination revealed a positive Murphy sign and peritoneal irritation. Laboratory data demonstrated that inflammatory marker levels were increased. Abdominal ultrasonography showed that blood flow in the cystic artery was reduced and the gallbladder was swollen. Abdominal contrast-enhanced computerized tomography indicated that the swollen gallbladder was modestly enhanced and the fundus was displaced under the midline and detached from the gallbladder bed. The cystic duct was twisted. Magnetic resonance cholangiopancreatography showed that the root of the cystic duct was unclear and the extrahepatic bile duct had V-shaped distortion. The gallbladder neck showed a tapering interruption with the common biliary duct. We made a preoperative diagnosis of gallbladder torsion. Accordingly, emergency laparoscopic cholecystectomy was performed. The intraoperative findings included a dark swollen gallbladder that was twisted in the counterclockwise direction. The patient was discharged without any postoperative complications on day 7., Discussion: Combined acute onset of abdominal pain with characteristic radiological findings made it possible to precisely diagnose gallbladder torsion., Conclusion: Laparoscopic cholecystectomy can be the gold standard treatment for gallbladder torsion after a preoperative diagnosis is made., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)