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Background: New diagnostic criteria have recently been established to classify small-for-size syndrome (SFSS) after living donor liver transplantation into 3 groups based on severity. This study aimed to evaluate the clinical impact of grade A SFSS and identify the mortality risk., Methods: We collected data from 406 patients diagnosed with grade A SFSS after living donor liver transplantation. Grade A SFSS is characterized by total bilirubin >5 mg/dL on postoperative day (POD) 7 or total bilirubin >5 mg/dL or ascites >1 L/d on POD 14. After propensity score matching, 193 patients were categorized into the up-trend group, down-trend group, and ascites group, with 43 patients (22.3%) in the up-trend group (total bilirubin on POD 7 < POD 14), 107 patients (55.4%) in the down-trend group (total bilirubin on POD 7 > POD 14), and 43 patients (22.3%) in the ascites group (only satisfying ascites criteria)., Results: There was no significant difference in survival between patients with grade A SFSS and those without SFSS (P = 0.152). The up-trend group showed a higher 90-d mortality rate than the down-trend and ascites groups (P = 0.025). The 1-y survival rate differed significantly between the groups (87.6%, 91.9%, and 97.7%, respectively; P = 0.044). The independent risk factors for survival were up-trend of total bilirubin, recipient age (65 y and older), model for end-stage liver disease score (≥30), and ABO incompatibility. Patients with ≥2 risk factors had worse survival rates than those with none and only 1 risk factor (P < 0.001)., Conclusions: Although the survival rate was comparable between the grade A SFSS and non-SFSS cohorts, the up-trend group showed worse survival. Aggressive interventions should be considered for up-trend patients with risk factors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The relationship between patterns of outpatient oral loop diuretic (LD) dose reduction and prognosis in patients with heart failure (HF) remains unclear., Methods: We evaluated 679 patients with HF-prescribed LDs at baseline between September 2015 and August 2019. Dose reduction was defined as a change to a lower LD dose than the previous outpatient dose. Dose intensification was defined as a change to a higher LD dose than the previous outpatient dose. Patients were classified into no-reduction (no LD dose reduction during follow-up) and reduction groups (categorized into successive-reduction [≥2 successive LD dose reductions without intervening LD dose intensification] and single-reduction [LD dose reduction without successive dose reduction] groups). The primary outcomes were all-cause death, HF hospitalization (HFH), and the composite of cardiovascular death (CVD) or HFH., Results: Within a median follow-up of 53.7 (range, 2.6-99.1) months, 156 deaths were recorded: 121 (29 %), 31 (15 %), and three (4 %) patients in the no-reduction (n = 411), single-reduction (n = 195), and successive-reduction (n = 73) groups, respectively. After adjusting for cofounders, the reduction group had a lower risk of primary outcomes than the no reduction group (all-cause death: hazard ratio (HR) = 0.65, 95 % confidence interval (CI) = 0.44-0.96; CVD or HFH: HR=0.69, 95 %CI=0.52-0.93; HFH: HR=0.69, 95 % CI=0.52-0.93). The successive-reduction group had a lower risk of the composite of CVD or HFH (HR=0.26, 95 % CI: 0.10-0.67) and HFH (HR=0.34, 95 % CI=0.13-0.86) than the single-reduction group., Conclusions: Outpatient LD dose reduction patterns can be indicators of good prognosis in HF patients., Competing Interests: 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., (© 2024 The Author(s).)

Purposes: The optimal surgical technique and perioperative management to prevent postoperative pancreatic fistula (POPF) formation after pancreaticoduodenectomy have not yet been established. This study examined the perioperative outcomes of pancreaticogastrostomy with endoscopic transgastric drainage., Methods: We performed a retrospective analysis of 191 patients who underwent pancreaticoduodenectomy between 2016 and 2023. They were divided into two groups: pancreaticojejunostomy group (n = 135) and pancreaticogastrostomy group (n = 56). We compared preoperative factors and postoperative outcomes. We performed endoscopic drainage only in the pancreaticogastrostomy group., Results: Preoperative factors were similar between the two groups. Operative time [480 (404-542) vs. 382 (346-458) minutes], blood loss [505 (270-850) vs. 315 (145-535) g], pseudoaneurysm formation (7 % vs. 0 %), and postoperative hospital stay [28 (22-38) vs. 19 (17-24) days] were significantly lower in the pancreaticogastrostomy group. In the analysis of 41 patients with POPF, postoperative hospital stay [40 (23-108) vs. 27 (18-54) days] and hospital stay after POPF diagnosis [30 (10-99) vs. 15 (5-35) days] were significantly shorter in the pancreaticogastrostomy group. Endoscopic transgastric drainage was performed in 77 % of patients in the pancreaticogastrostomy group, and drainage was successfully completed in all patients., Conclusion: Pancreaticogastrostomy with endoscopic transgastric drainage could be effective for the safe management of pancreaticoduodenectomy., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/aim: No studies have investigated the advantage of laparoscopic hepatectomy (LH) compared with open hepatectomy (OH) from a nutritional perspective. This study aimed to compare the postoperative nutritional status between LH and OH., Patients and Methods: A total of 186 patients who underwent partial hepatic resection for liver tumors were analyzed retrospectively. We compared perioperative variables between LH and OH. The nutritional status was assessed using serum albumin (Alb) and rapid turnover protein concentrations. We investigated risk factors for postoperative malnutrition using univariate and multivariate analyses., Results: The LH group, compared with the OH group, had a significantly shorter operative time (239 vs. 344 min, p<0.03), less intraoperative blood loss (100 vs. 343 g, p<0.01), and a shorter length of postoperative stay (8 vs. 11 days, p<0.01). Postoperative serum Alb and prealbumin concentrations in the LH group were significantly higher than those in the OH group (3.4 vs. 3.2 g/dl, p<0.01; 15.0 vs. 12.0 mg/dl, p=0.02, respectively). The multivariate analysis showed that OH (p=0.02) and hepatocellular carcinoma (p<0.01) were significant and independent risk factors for postoperative malnutrition., Conclusion: LH may be superior to OH in terms of the postoperative nutritional status, intraoperative blood loss, and length of postoperative stay., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The study aimed to investigate the efficacy of radiotherapy or chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer., Patients and Methods: Twenty-eight patients who had isolated locoregional recurrence after pancreatectomy for pancreatic cancer between 2007 and 2021 were retrospectively analyzed. We investigated the effect of the treatment method [radiotherapy or chemoradiotherapy (radiotherapy with concurrent chemotherapy)] on progression-free survival (PFS) and post-recurrence survival (PRS)., Results: The median disease-free survival was 16.1 months (range=4.7-47.1 months). Five patients received radiotherapy and 21 patients received chemoradiotherapy [radiotherapy concurrent with gemcitabine (GEM) or S-1] for locoregional recurrence. All patients except one patient with interstitial pneumonia were treated with salvage chemotherapy after irradiation. The median PFS rates of the radiotherapy group and the chemoradiotherapy group were 2.8 months (range=1.5-5.4 months) and 16.8 months (range=2.7-42.8 months), respectively. The median PRS rates were 23.7 months (range=8.1-26.4 months) for the radiotherapy group and 26.2 months (range=6.0-64.7 months) for the chemoradiotherapy group. Multivariate analysis identified radiotherapy [hazard ratio (HR)=12.2, 95% confidence interval (CI)=3.29-45.6, p<0.001] and serum DUPAN-2 >150 U/ml (HR=2.90, 95%CI=1.22-6.93, p=0.02) as independent predictors of PFS, and UICC TNM Stage ≥III (HR=3.23, 95%CI=1.17-8.96, p=0.02) and modified Glasgow prognostic score before the treatment for the recurrence 1 or 2 (HR=3.05, 95%CI=1.15-8.08, p=0.03) as independent predictors of PRS., Conclusion: Chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer could suppress re-recurrence more effectively than radiotherapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: This study aimed to investigate the effects of changes in clinicopathological factors during preoperative chemotherapy for pancreatic cancer, including skeletal muscle volume, on recurrence and prognosis after pancreatectomy., Methods: Data from 41 patients who underwent resection for pancreatic cancer after preoperative chemotherapy from 2012 to 2021 were retrospectively reviewed. Skeletal muscle volume was substituted for the psoas muscle area (PMA) at the level of the third lumbar vertebra. We investigated the relationship of clinicopathological factors during preoperative chemotherapy with disease-free survival (DFS) and overall survival (OS). The association between clinicopathological factors and a decrease in PMA was investigated., Results: In the multivariate analyses for DFS and OS, the factors associated with recurrence were as follows: decrease in PMA ( P = 0.003) and the absence of adjuvant therapy ( P = 0.03), and the factors associated with poor prognosis were as follows: decrease in PMA ( P = 0.04) and the absence of adjuvant therapy ( P = 0.008), and the resectability of borderline resectable and unresectable-locally advanced tumors ( P = 0.033). All patients with partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1) had no decrease in PMA ( P = 0.01). The proportion of patients with Evans classification ≥ II was significantly higher in the group without a decrease in PMA ( P = 0.02). The proportion of patients with an average relative dose intensity of adjuvant therapy ≥0.6 was significantly higher in the group without a decrease in PMA ( P = 0.02)., Conclusion: Changes in preoperative skeletal muscle volume during preoperative chemotherapy for pancreatic cancer is a potential predictor of recurrence and prognosis after pancreatectomy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study aimed to identify the prognostic factors after pancreatectomy for borderline resectable pancreatic cancer abutting major arteries (BR-A). Methods: We retrospectively investigated relationship between preoperative and intraoperative variables and overall survival (OS) through univariate and multivariate analyses. The cut-off points of preoperative therapy duration and response rates of serum carbohydrate antigen 19-9 (CA19-9) levels after preoperative therapy were determined through a minimum P -value approach using the log-rank test for OS. Overall survival was compared among patients stratified according to the independent prognostic factors and the presence or absence of pancreatectomy. Results: After pretreatment, 17 patients underwent pancreatectomy and four patients continued chemotherapy without surgery. Multivariate analysis in 17 resected BR-A patients demonstrated decreased serum CA19-9 levels and preoperative therapy duration of ≥4 months were the independent prognostic factors [hazard ratio (HR) 0.01; P = 0.002, HR 0.13; P = 0.02]. Patients who underwent surgery with decreased serum CA19-9 levels after preoperative therapy of ≥4 months had a significantly better prognosis than those without one or both of independent prognostic factors and those who did not undergo surgery (median survival time: not estimated, 23.3 months, 10.5 months, and 10.8 months; P = 0.02, P = 0.004, and P = 0.001, respectively). Furthermore, the prognosis did not significantly differ between the patients who underwent surgery without meeting either one or both criteria and those without surgery. Conclusions: Preoperative therapy duration of ≥4 months and decreased serum CA19-9 levels are independent prognostic factors among BR-A patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Abdominal aortic calcification (AAC), an indicator of systemic arteriosclerosis, is associated with short- and long-term outcomes in malignancies. We investigated the prognostic impact of AAC in patients who underwent hepatectomy for intrahepatic cholangiocarcinoma (IHCC)., Methods: The study cohort comprised 46 patients who underwent hepatectomy for IHCC between January 2008 and September 2020. The AAC volume measured by preoperative computed tomography was used to construct a model of the calcified segment from the renal artery to the common iliac artery bifurcation. We investigated the relationship between AAC and the long-term outcomes. The AAC volume cutoff value was calculated from a receiver-operating characteristic curve based on the three-year survival., Results: According to our cutoff AAC volume of 3,700 mm 3 , 11 patients (24%) had high AAC volumes. The high-AAC group was significantly older than the low-AAC group (73 vs. 62 years old, p < 0.01). A multivariate analysis of the cancer-specific survival showed that a high serum carbohydrate antigen 19-9 concentration (hazard ratio [HR] 5.57, p = 0.01), high AAC volume (HR 3.03, p = 0.04), and [high?] T3 or T4 levels (HR 9.05, p < 0.01) were independently associated with a poor prognosis., Conclusion: AAC is a useful predictor of the oncological prognosis in patients undergoing hepatectomy for IHCC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant ( P interaction = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; P interaction = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.

Background: This study aimed to identify postoperative recurrence and prognostic factors, including osteosarcopenia for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer and to examine the impact of postoperative pancreatic enzyme replacement therapy (PERT)., Methods: We retrospectively examined 32 resected patients with BR and UR-LA pancreatic cancer. We investigated independent factors in the disease-free survival and overall survival. The relation of osteosarcopenia with the clinicopathological factors was investigated. Additionally, the association of the administration of a standard dose of pancrelipase, the amount of lipase required for patients with pancreatic exocrine insufficiency, for ≥6 months postoperatively with improvement of sarcopenia, osteopenia, and osteosarcopenia and completion rate of adjuvant chemotherapy was investigated., Results: Multivariate analyses identified osteosarcopenia ( P = 0.049) and lymph node metastasis ( P = 0.01) as independent recurrence predictors, and osteosarcopenia ( P = 0.002), maximum tumor diameter ≥40 mm ( P = 0.006), and no adjuvant therapy ( P = 0.01) as independent prognostic predictors. In the osteosarcopenia group, serum CA19-9 levels were higher ( P = 0.03). The administration of a standard dose of pancrelipase for ≥6 months postoperatively was none in the osteosarcopenia group (0% vs 42.9%, P = 0.01), while significantly improved postoperative sarcopenia (33% vs 0%, P = 0.004), increased number of cycles of adjuvant chemotherapy (n = 6 vs n = 3, P = 0.03), and the completion rate of adjuvant chemotherapy in excluding cases interrupted because of recurrence (86% vs 25%, P = 0.007)., Conclusions: Osteosarcopenia was an independent recurrent and prognostic factor in patients after pancreatectomy for locally advanced pancreatic cancer. Appropriate postoperative PERT may contribute to a better prognosis by improving sarcopenia and increasing the completion rate of adjuvant chemotherapy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index is a novel immune nutrition scoring system associated with cancer prognosis. This study investigated the association between the CALLY index and the long-term outcomes of patients with gastric cancer., Methods: We included 175 patients with gastric cancer who underwent curative gastrectomies at the Department of Surgery, International University of Health and Welfare Hospital between January 2011 and October 2019. The CALLY index was calculated based on the levels of serum albumin, serum CRP, and peripheral lymphocyte count. Utilizing both univariate and multivariate analyses, the prognostic value of the CALLY index was investigated., Results: In the multivariate analyses, disease stage (hazard ratio [HR], 7.85; 95% confidence interval [CI], 3.31-18.6; P < .01), microvascular invasion (HR, 2.88; 95% CI, 1.30-6.36; P < .01), and low CALLY index (HR, 2.18; 95% CI, 1.00-4.76; P = .05) were independent and significant predictors of disease-free survival. Low body mass index (HR, 4.15; 95% CI, 1.63-10.6; P < .01), advanced disease stage (HR, 8.22; 95% CI, 3.47-19.5; P < .01), and low CALLY index (HR, 3.00; 95% CI, 1.3-6.93; P = .01) were independent and significant predictors of overall survival. The low CALLY index group had a lower body mass index ( P < .01), advanced disease stage ( P < .01), and a higher Glasgow prognostic score ( P < .01)., Conclusions: The CALLY index may be associated with a poor prognosis for gastric cancer, highlighting the utility of a comprehensive assessment using inflammatory, nutritional, and immunological statuses., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Atherosclerosis and cancer may progress through common pathological factors. This study was performed to investigate the association between the abdominal aortic calcification (AAC) volume and outcomes following surgical treatment for pancreatic cancer., Methods: The subjects of this retrospective study were 194 patients who underwent pancreatic cancer surgery between 2007 and 2020. The AAC volume was assessed through routine preoperative computed tomography. Univariate and multivariate analyses were performed to evaluate the impact of the AAC volume on oncological outcomes., Results: A higher AAC volume (≥ 312 mm 3 ) was identified in 66 (34%) patients, who were significantly older and had a higher prevalence of diabetes and sarcopenia. Univariate analysis revealed several risk factors for overall survival (OS), including male sex, an AAC volume ≥ 312 mm3, elevated carbohydrate antigen 19-9, prolonged operation time, increased intraoperative bleeding, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy. Multivariate analysis identified an AAC volume ≥ 312 mm3, prolonged operation time, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy as independent OS risk factors. The OS rate was significantly lower in the high AAC group than in the low AAC group., Conclusion: The AAC volume may serve as a preoperative prognostic indicator for patients with pancreatic cancer., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Although the frequency of community-acquired infections caused by Klebsiella pneumoniae subsp. ozaenae (K. ozaenae) is low, they are often detected in sputum specimens. In addition, lung abscesses, necrotizing pneumonia, and urinary tract infections caused by K. ozaenae have also been reported. We herein report the first detection of K. ozaenae as an etiological agent of bacterial meningitis in Japan. Cases of K. ozaenae meningitis complicated by diabetes mellitus and sinusitis have been reported elsewhere. When Klebsiella pneumoniae is detected in such cases, it is important to use other detection methods in addition to mass spectrometry for correct identification.

Background: Owing to advances in the multidisciplinary treatment of hepatocellular carcinoma (HCC), a conceptualization and definition for borderline resectable (BR) HCC, which carries a high risk of recurrence, is warranted. In this study, we aimed to define BR-HCC using a prognosis-oriented approach., Study Design: The study included an original cohort of 221 patients and an independent validation cohort of 181 patients who had undergone primary hepatic resection for HCC. To define biological BR-HCC, we evaluated the risk factors for early recurrence beyond the Milan criteria within 1 year after hepatic resection using multivariable logistic regression models. Subsequently, we developed high-risk scores using the identified risk factors and defined BR-HCC. The utility of high-risk score was validated in the validation cohort., Results: In the original cohort (hepatitis B virus:hepatitis C virus = 20%:29%), recurrence beyond the Milan criteria within 1 year was observed in 28 patients (13%), with a 5-year survival rate of 25%. Multivariable analysis identified risk factors for recurrence beyond the Milan criteria within 1 year, including serum alpha-fetoprotein levels of 12 ng/mL or more (p = 0.02), tumor diameters less than 5 cm (p = 0.02), tumor number 3 or more (p = 0.001), and macrovascular invasion (p = 0.04). BR-HCC was defined as a tumor with 2 or more identified risk factors, and 42 patients (19%) were diagnosed with BR-HCC, with a 5-year survival rate of 51%. In the validation cohort, 45 (25%) patients had BR-HCC, with a 5-year survival rate of 42%., Conclusions: The prognosis-oriented definition of BR-HCC enabled us to identify patients who are susceptible to early unresectable recurrence and have poor survival after hepatic resection for HCC. For patients with BR-HCC, preoperative systemic therapy may be a viable option to improve postresection outcomes., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis even after curative-intent hepatic resection due to a high recurrence rate. The aim of this study was to investigate preoperative risk factors for early recurrence after surgery for ICC, which may help to identify patients who need preoperative chemotherapy., Methods: We retrospectively analyzed 51 patients who had undergone primary surgery for ICC. We investigated the association of preoperative clinical variables with recurrence within 1 year after resection for ICC. We then created a high-risk ICC score using the identified preoperative factors and investigated the association of the score with disease-free and overall survival., Results: Recurrence within 1 year after surgery for ICC was significantly associated with poor overall survival ( P < .01). In the multivariate analysis, preoperative tumor size > 5 cm ( P = .03) and elevated C-reactive protein-to-albumin ratio (CAR) ( P = .04) were significantly associated with recurrence within 1 year after surgery. A high-risk ICC score of 2 was associated with poor disease-free survival ( P < .01) and overall survival ( P = .02) compared with a score of 0 or 1., Conclusions: Our high-risk ICC score, combining preoperative tumor size and CAR, can be an indicator of early recurrence and poor survival in patients after hepatic resection for ICC. Our findings may provide better preoperative risk stratification of patients with ICC, and the high-risk ICC patients may benefit from preoperative therapy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/aim: With the aging of the population, there is a rising proportion of elderly patients undergoing liver resection. However, the safety and efficacy of laparoscopic liver resection (LLR) in the elderly have not yet been established. In this study, we compared the short-term results of LLR and open liver resection (OLR) in elderly patients using propensity score matched (PSM) analysis., Patients and Methods: The study comprised 237 elderly patients aged 65 years and older who had undergone liver resection between 2015 to 2021, excluding biliary and vascular reconstruction and simultaneous surgeries other than liver resection. We conducted PSM analysis for baseline characteristics (age, sex, BMI, ASA-PS, disease, procedure, tumor size, and number of tumors) to eliminate potential selection bias. We then compared short-term postoperative outcomes between LLR and OLR groups in patients selected by PSM analysis., Results: Applying PSM analysis, 90 cases each were selected for the LLR and OLR groups. The LLR group had a significantly lower complication rate (Clavien-Dindo: CD ≥II) (19% vs. 33%, p=0.03), especially bile leakage (CD ≥II) (0% vs. 6.7%, p=0.03) compared with those in the OLR group. In addition, a shorter operation time (244 min vs. 351 min, p<0.01), less blood loss (150 ml vs. 335 ml, p<0.01), and shorter hospital stay (8 days vs. 12 days, p<0.01) were observed in the LLR group. No operative or in-hospital deaths were observed in both groups., Conclusion: LLR can be safely performed in elderly patients and offers better short-term outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To test hypotheses that appendectomy history might lower long-term colorectal cancer risk and that the risk reduction might be strong for tumors enriched with Fusobacterium nucleatum, bacterial species implicated in colorectal carcinogenesis., Background: The absence of the appendix, an immune system organ and a possible reservoir of certain pathogenic microbes, may affect the intestinal microbiome, thereby altering long-term colorectal cancer risk., Methods: Utilizing databases of prospective cohort studies, namely the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of appendectomy history with colorectal cancer incidence overall and subclassified by the amount of tumor tissue Fusobacterium nucleatum​​ (Fusobacterium animalis). We used an inverse probability weighted multivariable-adjusted duplication-method Cox proportional hazards regression model., Results: During the follow-up of 139,406 participants (2,894,060 person-years), we documented 2811 incident colorectal cancer cases, of which 1065 cases provided tissue F. nucleatum analysis data. The multivariable-adjusted hazard ratio of appendectomy for overall colorectal cancer incidence was 0.92 (95% CI, 0.84-1.01). Appendectomy was associated with lower F. nucleatum-positive cancer incidence (multivariable-adjusted hazard ratio, 0.53; 95% CI, 0.33-0.85; P=0.0079), but not F. nucleatum-negative cancer incidence (multivariable-adjusted hazard ratio, 0.98; 95% CI, 0.83-1.14), suggesting a differential association by F. nucleatum status (Pheterogeneity=0.015). This differential association appeared to persist in various participant/patient strata including tumor location and microsatellite instability status., Conclusions: Appendectomy likely lowers the future long-term incidence of F. nucleatum-positive (but not F. nucleatum-negative) colorectal cancer. Our findings do not support the existing hypothesis that appendectomy may increase colorectal cancer risk., Competing Interests: A.T.C. previously served as a consultant for Bayer Healthcare and Pfizer Inc. M.G. was on an advisory board for AstraZeneca and receives research funding from Bristol-Myers Squibb. J.A.M. has served as an advisor/consultant to Merck Pharmaceuticals and COTA Healthcare. K.W. is currently a stakeholder and employee of Vertex Pharmaceuticals. This study was not funded by any of these commercial entities. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: Laparoscopic hepatic resection is currently used for ruptured hepatocellular carcinoma (HCC); however, it is technically challenging. We developed and implemented surgical strategies for emergency laparoscopic partial liver resection in selected patients with peripheral lesions who were hemodynamically stable and without severe liver dysfunction., Patients and Methods: The surgical techniques used were as follows. First, the Pringle maneuver was performed to control hepatic blood inflow (step 1). Next, strong hemostatic agents were applied at the rupture point of the tumor (step 2). The hanging tape was positioned along the dorsal side of the resection line to control the partial blood inflow and outflow of the tumor, as well as to expose the surgical plane (step 3). The liver parenchyma was dissected along the hanging tape (step 4). We performed emergency laparoscopic partial liver resection in three patients who were in a pre-shock status., Results: The tumors were located in segments 6 (cases 1 and 2) and 2 (case 3). The tumor diameters were 90, 62, and 80 mm. The Preoperative Child-Pugh scores were B7, B9, and B8. The hemostatic products performed well and controlled bleeding from the ruptured HCC. The hanging tape facilitated the dissection of the liver parenchyma. The operative time and intraoperative blood loss were 135 min and 400 ml, 266 min and 200 ml, and 191 min and 495 ml for cases 1, 2, and 3 respectively. There were no in-hospital deaths., Conclusion: Emergency laparoscopic partial liver resection could be an option for patients with ruptured HCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Data support that enterotoxigenic Bacteroides fragilis (ETBF) harbouring the Bacteroides fragilis toxin (bft) gene may promote colorectal tumourigenesis through the serrated neoplasia pathway. We hypothesized that ETBF may be enriched in colorectal carcinoma subtypes with high-level CpG island methylator phenotype (CIMP-high), BRAF mutation, and high-level microsatellite instability (MSI-high)., Methods: Quantitative PCR assays were designed to quantify DNA amounts of Bacteroides fragilis, ETBF, and each bft gene isotype (bft-1, bft-2, or bft-3) in colorectal carcinomas in the Health Professionals Follow-up Study and Nurses' Health Study. We used multivariable-adjusted logistic regression models with the inverse probability weighting method., Results: We documented 4476 colorectal cancer cases, including 1232 cases with available bacterial data. High DNA amounts of Bacteroides fragilis and ETBF were positively associated with BRAF mutation (p ≤ 0.0003), CIMP-high (p ≤ 0.0002), and MSI-high (p < 0.0001 and p = 0.01, respectively). Multivariable-adjusted odds ratios (with 95% confidence interval) for high Bacteroides fragilis were 1.40 (1.06-1.85) for CIMP-high and 2.14 (1.65-2.77) for MSI-high, but 1.02 (0.78-1.35) for BRAF mutation. Multivariable-adjusted odds ratios for high ETBF were 2.00 (1.16-3.45) for CIMP-high and 2.86 (1.64-5.00) for BRAF mutation, but 1.09 (0.67-1.76) for MSI-high. Neither Bacteroides fragilis nor ETBF was associated with colorectal cancer-specific or overall survival., Discussion: The tissue abundance of Bacteroides fragilis is associated with CIMP-high and MSI-high, whereas ETBF abundance is associated with CIMP-high and BRAF mutation in colorectal carcinoma. Our findings support the aetiological relevance of Bacteroides fragilis and ETBF in the serrated neoplasia pathway., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study examined the impact of osteosarcopenia on recurrence and the prognosis after resection for extrahepatic biliary tract cancer (EBTC)., Methods: We retrospectively analyzed 138 patients after resection for perihilar cholangiocarcinoma (11), distal cholangiocarcinoma (54), gallbladder carcinoma (30), or ampullary carcinoma (43). Osteosarcopenia is defined as the concomitant occurrence of osteopenia and sarcopenia. We investigated the relationship between osteosarcopenia and the overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses., Results: Osteosarcopenia was identified in 38 patients (27.5%) before propensity score (PS) matching. In the multivariate analysis, the independent recurrence factors were the prognostic nutrition index (p = 0.015), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.004), perineural invasion (p = 0.002), and non-curability (p = 0.008), whereas the independent prognostic factors were prognostic nutrition index (p = 0.030), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.007), lymphatic invasion (p = 0.018), and non-curability (p = 0.004). After PS matching, there was no significant difference in the variables between the patients with and without osteosarcopenia (n = 34 each). The 5-year DFS and OS after PS matching in patients with osteosarcopenia were significantly worse than in patients without osteosarcopenia (17.6% vs. 38.8%, p = 0.013 and 20.6% vs. 57.4%, p = 0.0005, respectively)., Conclusions: Preoperative osteosarcopenia could predict the DFS and OS of patients after resection for EBTC., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: Simultaneous dual hepatic vein embolization (DHVE) has been proposed for safe right-sided hepatectomy, with good results for liver hypertrophy and function. However, the histological and radiological findings of DHVE have not been thoroughly investigated., Methods: This study included 14 patients who underwent DHVE before right-sided major hepatectomy. DHVE was performed if the future liver remnant was < 35% or borderline, but with concomitant vascular resection. The liver function was assessed using the signal intensity on Gd-EOB-DTPA-MRI. A histological evaluation of the area of DHVE and portal vein embolization (PVE) were performed., Results: The median pre- and post-functional liver remnants were 363 ml and 498 ml, respectively (p < 0.001). The median growth rate was 48.6%, and there was no post-hepatectomy liver failure in the patients who underwent DHVE. The signal intensity ratio in the area of DHVE was lower than that in the areas of PVE and the remnant liver (p < 0.01). The degree of congestion and necrosis was greater in the area of DHVE than in the area of PVE alone (p < 0.01 and p = 0.04, respectively)., Conclusions: We observed good liver hypertrophy after DHVE and histological and radiological changes in the area of DHVE. Our findings provide a compelling rationale for further investigation of the mechanism of liver hypertrophy in DHVE., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: We investigated the prognostic impact of osteosarcopenia, defined as the combination of osteopenia and sarcopenia, in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC)., Methods: The relationship of osteosarcopenia with disease-free survival and overall survival was analyzed in 183 patients who underwent elective pancreatic resection for PDAC. Computed tomography was used to measure the pixel density in the midvertebral core of the 11th thoracic vertebra for evaluation of osteopenia and in the psoas muscle area of the 3rd lumbar vertebra for evaluation of sarcopenia. Osteosarcopenia was defined as the simultaneous presence of both osteopenia and sarcopenia. The study employed a retrospective design to examine the relationship between osteosarcopenia and survival outcomes., Results: Osteosarcopenia was identified in 61 (33%) patients. In the univariate analysis, disease-free survival was significantly worse in patients with male sex (p = 0.031), pathological stage ≥ III PDAC (p = 0.001), NLR, ≥ 2.71 (p = 0.041), sarcopenia (p = 0.027), osteopenia (p = 0.001), and osteosarcopenia (p < 0.001), and overall survival was significantly worse in patients with male sex (p = 0.001), pathological stage ≥ III PDAC (p = 0.001), distal pancreatectomy (p = 0.025), sarcopenia (p = 0.003), osteopenia (p < 0.001), and osteosarcopenia (p < 0.001). In the multivariate analysis, the independent predictors of disease-free survival were osteosarcopenia (p < 0.001) and pathological stage ≥ III PDAC (p = 0.002), and the independent predictors of overall survival were osteosarcopenia (p < 0.001), male sex (p = 0.006) and pathological stage ≥ III PDAC (p = 0.001)., Conclusion: Osteosarcopenia has an adverse prognostic impact on long-term outcomes in patients undergoing pancreatic resection for PDAC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been associated with prognosis in patients with hepatocellular carcinoma (HCC). We hypothesized that dynamic changes in CXI might be associated with long-term outcomes in HCC., Methods: This study comprised 131 patients who had undergone primary hepatic resection for HCC between 2008 and 2019. Preoperative CXI (pre-CXI) and postoperative CXI (post-CXI) were calculated by the following formula: skeletal muscle index x serum albumin level / neutrophil-to-lymphocyte ratio. Pre- and post-CXI were classified into two groups (high vs. low). We retrospectively investigated the association of perioperative dynamic changes in CXI with disease-free and overall survival., Results: In multivariate analyses, negative HBs-antigen ( p  = 0.02), high serum PIVKA-II level ( p  < 0.01), poor tumor differentiation ( p  = 0.02), multiple tumors ( p  < 0.01), microvascular invasion ( p  < 0.01), partial resection ( p  < 0.01), postoperative complications ( p  < 0.01), and low-pre-CXI ( p  < 0.01) were significant predictors of disease-free survival, while high ICG R15 ( p  = 0.01), poor tumor differentiation ( p  < 0.01), multiple tumors ( p  = 0.01), postoperative complications ( p  < 0.01), low-pre-CXI ( p  < 0.01), and low-post-CXI ( p  < 0.01) were significant predictors of overall survival. Low-post-CXI was associated with older age ( p  = 0.045), larger tumor ( p  < 0.01), longer operation time ( p  = 0.047), greater intraoperative bleeding ( p  < 0.01), and intraoperative blood transfusion ( p  < 0.01). Moreover, dynamic changes in CXI were associated with overall survival in each subgroup of patients with low-pre-CXI ( p  = 0.02) or high-pre-CXI ( p  = 0.03)., Conclusions: Not only post-CXI but also dynamic changes in CXI from pre- to post-hepatectomy can be a prognostic indicator of HCC, providing a compelling rationale for aggressive perioperative nutritional and physical interventions to improve long-term outcomes., Competing Interests: The authors declare no conflict of interests for this article., (© 2024 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed procedure in bariatric-metabolic surgery (BMS) worldwide, accounting for approximately 90% of BMS procedures in Japan. While numerous studies have reported on the safety and efficacy of LSG, gastroesophageal reflux disease (GERD) remains a major postoperative complication. Although Roux-en-Y gastric bypass (RYGB) is preferred for severe obesity with GERD, it is less suitable for Japanese patients who have a higher risk of gastric cancer due to the remnant stomach which is difficult to observe with esophago-gastro-duodenoscopy. To address de novo and exacerbation GERD after LSG, we conducted LSG with Toupet fundoplication (T-sleeve) for Japanese patients with severe obesity. In our first T-sleeve case, the patient demonstrated sufficient weight loss and improved GERD following surgery. Hence, we suggest that T-sleeve is a feasible option for Japanese patients with obesity and concurrent GERD., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background/aim: This study aimed to identify the risk factors for early recurrence (ER) after pancreatic ductal adenocarcinoma (PDAC) resection to create a novel scoring system for ER and analyze their effect on the recurrence pattern., Patients and Methods: Sixty patients with PDAC who underwent pancreatectomy were included. The predicted risk factors for ER were analyzed. A new score defining ER was created and analyzed for recurrence pattern and prognosis., Results: Independent predictors included high CA 19-9 (≥147 U/ml), high lymph node ratio (LNR of ≥0.1277), and no adjuvant chemotherapy (AC). The 5-year overall survival rates with a score of 0, 1, and 2 were 55.8%, 11.0%, and 0%, respectively. In the moderate- risk score group, prognosis was improved by induction of AC within 58 days., Conclusion: Preoperative high CA19-9, high LNR, and no AC could be ER predictors. Induction of postoperative chemotherapy within 58 days may improve prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Signal intensity ratio of pancreas to spleen (SI ratio p/s ) on fat-suppressed T1-weighted images of magnetic resonance imaging has been associated with pancreatic exocrine function. We here investigated the predictive value of the SI ratio p/s for the development of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD)., Materials and Methods: This study comprised 208 patients who underwent PD. NAFLD was defined as a liver-to-spleen attenuation ratio of <0.9 calculated by a computed tomography 1 year after surgery. SI ratio p/s was calculated by dividing the average pancreas SI by the spleen SI. We retrospectively investigated the association of clinical variables including the SI ratio p/s and NAFLD by univariate and multivariate analyses., Results: NAFLD after 1 year was developed in 27 patients (13%). In multivariate analysis, the SI ratio p/s < 1 ( P < 0.001) was an independent predictor of incidence of NAFLD. The SI ratio p/s < 1 was associated with low amylase level of the pancreatic juice ( P < 0.001) and progressed pancreatic fibrosis ( P = 0.017). According to the receiver operating characteristics curve, the SI ratio p/s had better prognostic ability of NAFLD than the remnant pancreas volume., Conclusions: The SI ratio p/s is useful to predict NAFLD development after PD. Moreover, the SI ratio p/s can be a surrogate marker, which represents exocrine function of the pancreas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To study the effect of preoperative osteosarcopenia (OSP) on the prognosis of treatment (surgery or radiofrequency ablation (RFA)) in patients with Barcelona Cancer Liver Classification stage A hepatocellular carcinoma (BCLC A HCC)., Methods: This study enrolled 102 patients with BCLC A HCC who underwent surgical resection (n = 45) and RFA (n = 57); the patients were divided into two groups: OSP (n = 33) and non-OSP (n = 69). Overall survival (OS) and disease-free survival (DFS) curves for both the groups and treatment methods (surgery and RFA) were generated using the Kaplan-Meier method and compared using the log-rank test. Univariate analyses for OS and DFS were performed using log-rank test. Multivariate analyses were performed for factors that were significant at univariate analysis by Cox proportional hazard model., Results: Multivariate analysis showed that OSP (HR 2.44; 95 % CI 1.30-4.55; p < 0.01) and treatment (HR 0.57; 95 % CI 0.31-0.99; p = 0.05) were significant independent predictors of DFS; and treatment (HR, 0.30; 95 % CI 0.10-0.85; p = 0.03) was a significant independent predictor of OS in the non-OSP group, in which the OS rate was significantly lower in patients treated with RFA than in those treated by resection (p = 0.01)., Conclusions: OSP is a prognostic factor for BCLC A HCC treatment. Surgical approach was associated with a significantly better prognosis in patients without OSP compared to those who underwent RFA., Competing Interests: Declaration of competing interest The authors declare no Conflicts of Interest for this article., (Copyright © 2024. Published by Elsevier Ltd.)

Background/aim: This study aimed to investigate the relationship between prechemotherapy blood eicosapentaenoic acid (EPA) levels, sarcopenia, and overall survival in patients with pancreatic and biliary tract cancer undergoing chemotherapy., Patients and Methods: Forty-five patients with recurrent, non-resected pancreatic or biliary tract cancer undergoing chemotherapy were retrospectively analyzed. The skeletal muscle mass was measured at the third lumbar vertebra. Sarcopenia cut-off values were based on the Japanese Society of Hepatology sarcopenia assessment criteria. Two months after starting chemotherapy, the patients received enteral nutrition containing omega-3 fatty acids., Results: Patients with pancreatic and biliary tract cancers with low pre-treatment blood EPA levels had significantly more intense sarcopenia than those with high EPA levels (p=0.023). Patients with sarcopenia before chemotherapy had significantly lower overall survival than those without sarcopenia. Multivariate analysis revealed blood EPA concentration as an independent prognostic factor (p<0.01). Lumbar muscle volume, a marker of sarcopenia, showed a clear positive correlation with prechemotherapy EPA concentration (p=0.008). In patients administered with enteral nutrition containing omega-3 fatty acids, both EPA concentration and lumbar muscle volume were significantly higher than those prior to intervention, indicating sarcopenia improvement due to the intervention., Conclusion: In patients with recurrent non-resected pancreatic and biliary tract cancer, low blood EPA levels before chemotherapy are associated with sarcopenia and poor prognosis., Competing Interests: The Authors declare no conflicts of interest in relation to this study., (Copyright 2024, International Institute of Anticancer Research.)

Purpose: The preoperative platelet-to-lymphocyte ratio (PLR) has been reported as an important prognostic index for pancreatic ductal adenocarcinoma (PDAC); however, the significance of the postoperative (post-op) PLR for this disease has not been elucidated., Methods: We analyzed data on 118 patients who underwent pancreaticoduodenectomy for pancreatic head PDAC, collected from a prospectively maintained database. The post-op PLR was obtained by dividing the platelet count after surgery by the lymphocyte count on post-op day (POD) 14. The patients were divided into two groups according to a post-op PLR of < 310 or ≥ 310. Survival data were analyzed., Results: A high post-op PLR was identified as a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The post-op PLR remained significant, along with tumor differentiation and adjuvant chemotherapy, on multivariate analysis for OS (hazard ratio = 2.077, 95% confidence interval: 1.220-3.537; p = 0.007). The post-op PLR was a significant independent prognostic index for poor DFS, along with tumor differentiation and lymphatic invasion, on multivariate analysis (hazard ratio = 1.678, 95% confidence interval: 1.056-2.667; p = 0.028)., Conclusions: The post-op PLR in patients with pancreatic head PDAC was an independent predictor of DFS and OS after elective resection., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objective: The prognostic impact of occult vertebral fracture (OVF) in patients with malignancies is a new cutting edge in cancer research. This study was performed to analyze the prognostic impact of OVF after surgery for pancreatic cancer., Methods: This study involved 200 patients who underwent surgical treatment of pancreatic ductal adenocarcinoma. OVF was diagnosed by quantitative measurement using preoperative sagittal computed tomography image reconstruction from the 11th thoracic vertebra to the 5th lumbar vertebra., Results: OVF was diagnosed in 65 (32.5 %) patients. The multivariate analyses showed that male sex (p = 0.01), osteopenia (p < 0.01), OVF (p < 0.01), a carbohydrate antigen 19-9 level of ≥400 U/mL (p < 0.01), advanced stage of cancer (p < 0.01), and non-adjuvant chemotherapy (p = 0.02) were independent risk factors for overall survival. An age of ≥74 years (p < 0.01) and obstructive jaundice (p = 0.03) were independent risk factors for OVF. Furthermore, the combination of OVF and osteopenia further worsened disease-free survival and overall survival compared with osteopenia or OVF alone (p < 0.01; respectively)., Conclusion: Evaluation of preoperative OVF might be a useful prognostic indicator for patients with pancreatic ductal adenocarcinoma., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin. To overcome these issues, the identification of novel biomarkers is an unmet need., Objective: This study aimed to assess the usefulness of serum protein kinase C delta (PKCδ) for detecting these HCCs., Methods: PKCδ levels were measured using a sandwich enzyme-linked immunosorbent assay in 363 chronic liver disease (CLD) patients with and without HCC., Results: In both viral and non-viral CLD, PKCδ can detect HCCs with high sensitivity and specificity, particularly in the very early stages. Notably, the value and sensitivity of PKCδ were not modified by HCV elimination status. Liver injury and warfarin administration, which are known to cause false-positive results for conventional markers, did not modify PKCδ levels., Conclusions: PKCδ is an enhanced biomarker for the diagnosis of HCC that compensates for the drawbacks of conventional markers.

Background: The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5 years and early recurrence (within 1 year) is now recognized as having a poor prognosis and has limited treatment options., Methods: We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1 year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes., Results: Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1 year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis., Conclusions: In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Aim: Pancreatic ductal adenocarcinoma treatment is mainly based on the anatomical resectability classification. However, prognosis-based classification may be more reasonable. In this study, we stratified resectable pancreatic ductal adenocarcinoma according to preoperative factors and reconsidered treatment strategies., Methods: We retrospectively evaluated 131 patients who underwent upfront surgery for resectable pancreatic ductal adenocarcinoma between 2007 and 2019. Recurrence within 1 year after surgery was defined as early recurrence, and the risk factors for early recurrence were identified using preoperative factors. Subsequently, we calculated the scores and stratified the participant groups., Results: Fifty-five (42 %) patients who relapsed within 1 year showed significantly poorer survival than those without recurrence (median overall survival, 14.0 vs. 80.6 months; p < 0.01). Multivariate analysis revealed that a tumor diameter of ≥24 mm (p < 0.01) and preoperative serum carbohydrate antigen 19-9 level of ≥380 U/mL (p = 0.04) were the independent risk factors for early recurrence. Early recurrence score was created using these factors, stratifying the participant group into three groups of 0-2 points, and the prognosis was significantly different (median overall survival, 49.3 vs. 31.2 vs. 16.0 months; p < 0.01)., Conclusion: We stratified the upfront surgical cases of resectable pancreatic ductal adenocarcinoma. The group with a score of 0 had a good prognosis, and upfront surgery was possibly not futile on patients in poor general condition. The group with a score of 2 had a poor prognosis and may require stronger preoperative treatment., (Copyright © 2024. Published by Elsevier Ltd.)

Hypomagnesemia commonly occurs as a side effect of panitumumab treatment. In severe cases, temporary discontinuation or dose reduction of panitumumab may be necessary. Proton pump inhibitors (PPIs) are reportedly potential risk factors for hypomagnesemia. We conducted a multicenter study to assess the impact of PPIs on the risk of grade 3-4 hypomagnesemia in patients with metastatic colorectal cancer (mCRC) receiving panitumumab. We adjusted for potential bias using a propensity score-matched analysis and retrospectively reviewed the medical records of patients. Hypomagnesemia severity was graded according to the Common Terminology Criteria for Adverse Events, version 5.0. A total of 165 patients were enrolled in this study. The incidence of grade 3-4 hypomagnesemia was significantly higher in the PPI group than in the non-PPI group, both before (20.0% [30/60] vs. 8.0% [8/105], p = 0.026) and after propensity score matching (16.2% [6/37] vs. 0% [0/37], p = 0.025). In the propensity score-matched cohort, the risk of grade 3-4 hypomagnesemia was significantly higher in the PPI group (odds ratio, 2.19; 95% confidence interval, 1.69-2.84; p = 0.025). These findings suggest that concomitant use of PPIs significantly increases the risk of grade 3-4 hypomagnesemia in patients with mCRC receiving panitumumab. Therefore, close monitoring of these patients is imperative.

Background: Pancreatic cancer in contact with the superior mesenteric vein/portal vein is classified as resectable pancreatic cancer; however, the biological malignancy and treatment strategy have not been clarified., Methods: Data from 186 patients who underwent pancreatectomy for pancreatic cancer were evaluated using a prospectively maintained database. The patients were classified as having resectable tumors without superior mesenteric vein/portal vein contact and with superior mesenteric vein/portal vein contact of ≤180°. Disease-free survival, overall survival, and prognostic factors were analyzed., Results: In the univariate analysis, superior mesenteric vein/portal vein contact in resectable pancreatic cancer was a significant prognostic index for disease-free survival and overall survival. In the multivariate analysis for poor disease-free survival, the superior mesenteric vein/portal vein contact remained significant (hazard ratio = 2.13, 95% confidence interval: 1.29-3.51; p < 0.01). In the multivariate analysis, superior mesenteric vein/portal vein contact was a significant independent prognostic index for overall survival (hazard ratio = 2.17, 95% confidence interval: 1.27-3.70; p < 0.01), along with sex, tumor differentiation, nodal involvement, and adjuvant chemotherapy. Portal vein resection for superior mesenteric vein/portal vein contact did not improve the overall survival (p = 0.86)., Conclusions: Superior mesenteric vein/portal vein contact in resectable pancreatic cancer was found to be an independent predictor of disease-free survival and overall survival after elective resection. Thus, pancreatic cancer in contact with the superior mesenteric vein/portal vein may be considered as borderline resectable pancreatic cancer., 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 © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Anamorelin, a selective ghrelin receptor agonist, has been approved for pancreatic cancer treatment in Japan. We aimed to investigate whether systemic inflammation, represented by the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP)-albumin ratio (CAR), could predict the effect of anamorelin in patients with advanced pancreatic cancer., Methods: This study included 31 patients who had received anamorelin for advanced pancreatic cancer between 2021 and 2023. Patients' NLR, PLR, LMR, and CAR were evaluated before anamorelin administration. The patients were classified as responders and non-responders based on whether they gained body weight after 3 months of anamorelin administration. We investigated the association between systemic inflammation and anamorelin efficacy using a univariate analysis., Results: Twelve (39%) patients were non-responders. A high serum CRP level (p = 0.007) and high CAR (p = 0.013) was associated with non-response to anamorelin. According to the receiver operating characteristics analysis, the CAR cutoff value was 0.06, and CAR ≥ 0.06 was a risk factor (odds ratio, 5.6 [95% confidence interval 1.2-27.1], p = 0.032) for non-response to anamorelin., Conclusion: CAR can be a predictor of non-response to anamorelin in patients with advanced pancreatic cancer, suggesting the importance of a comprehensive assessment of the inflammatory status., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: The impact of occult vertebral fracture (OVF) on oncological outcomes after surgery has not been investigated, although its significance in orthopedics has been much debated recently. We evaluated the prognostic significance of OVF on the long-term outcomes of patients with colorectal liver metastases (CRLM) after hepatectomy., Methods: We included 140 patients with CRLM who underwent hepatectomy. OVF was identified using quantitative measurement and preoperative sagittal computed tomography image reconstruction from the 11th thoracic vertebra to the 5th lumber vertebra., Results: OVF was identified in 48 (34%) of the patients. In multivariate analysis, lymph node metastases ( p < 0.01), multiple tumors ( p = 0.02), extrahepatic lesions ( p < 0.01), OVF ( p < 0.01), intraoperative bleeding ( p = 0.04), and curability 1 or 2 ( p < 0.01) were independent and significant predictors of disease-free survival and extrahepatic lesions ( p < 0.01), osteosarcopenia ( p = 0.02), and OVF ( p < 0.01) were independent and significant predictors of overall survival. A higher age, adjuvant chemotherapy for a primary lesion before metachronous liver metastases, osteopenia, and hypoalbuminemia were independent risk factors for OVF., Conclusions: The evaluation of preoperative OVF is a useful prognostic factor for risk stratification and clinical decision-making for patients with CRLM.

Background: Laparoscopic hepatectomy after esophageal cancer surgery is a technically challenging procedure as it is difficult to control hepatic inflow due to adhesion 1. Ann Hepatobiliary Pancreat Surg. 22:344-349; 2. Dis Esophagus. 28:483-487; 3. Surg Endosc. 35:5375-5380; 4. Surg Laparosc Endosc Percutan Tech. 23:e103-105. Thus, we introduce our technique for hepatic inflow control using an endovascular clip., Methods: After the confirmation of space between the right and dorsal side of the hepatoduodenal ligament and the inferior vena cava, an endovascular clip was introduced laterally from the right side of the hepatoduodenal ligament to control hepatic inflow. The control of hepatic inflow was confirmed using intraoperative Doppler ultrasound and then a hepatic parenchymal transection was performed. The video demonstrates our technique using an endovascular clip for hepatic inflow control to perform safe open or laparoscopic hepatectomy after esophageal cancer surgery. Patient 1 was an 82-year-old woman with a history of laparoscopic assisted esophagectomy for esophageal neuroendocrine cancer. She underwent open anatomical resection of segment 3 for a 38-mm liver tumor. Patient 2 was a 71-year-old man with a history of laparoscopic esophagectomy for esophageal cancer. He underwent laparoscopic partial resection of segment 6 for a 24-mm liver tumor., Results: The operation times were 105 and 123 min, and the estimated blood loss was 30 g and 10 g, respectively. The patients' postoperative courses were uneventful and the patients were discharged on postoperative days 9 and 8, respectively., Conclusion: Right-lateral Pringle maneuver using an endovascular clip may be a safe and feasible technique in both open and laparoscopic hepatectomy after esophagectomy., (© 2023. Society of Surgical Oncology.)

Antibody-mediated rejection (AMR) after liver transplantation is uncommon but sometimes has a grave prognosis. We herein describe a 40-year-old man who developed simultaneous acute cellular rejection and acute AMR due to de novo donor-specific anti-human leukocyte antigen antibodies after living donor liver transplantation. He underwent living donor liver transplantation with his brother-in-law as the donor. Hepatic function deteriorated on postoperative day 6, and a liver biopsy revealed histologic findings of typical acute cellular rejection. However, steroid pulse therapy and thymoglobulin did not produce a clinical response, and his liver function dramatically deteriorated on postoperative day 13 (aspartate aminotransferase, 2787 IU/L; total bilirubin, 14.1 mg/dL). We diagnosed acute AMR based on positive immunohistochemical staining for C4d in portal areas and added plasma exchange and high-dose intravenous immunoglobulin after rituximab. The patient's clinical state improved and ultimately resolved. To our knowledge, this is the first report of dual antibody treatment for simultaneous acute cellular rejection and acute AMR induced by de novo donor-specific anti-human leukocyte antigen antibodies. Despite his fulminant clinical course, we successfully rescued the recipient with immediate anti-humoral therapy. The rapid treatment decision and adequate understanding of the mechanisms of anti-humoral therapy were crucial to overcoming acute AMR in this case., 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 © 2023 Elsevier Inc. All rights reserved.)

Obesity-related non-eosinophilic asthma has been identified as a phenotype of asthma. However, mepolizumab and omalizumab improve asthma control in severe asthma with obesity, implying that type-2 cytokines may be involved in the deterioration of control in obese asthma. Despite this, the clinical details of obese asthma with positive type-2 inflammation markers have not yet been reported. The objective of this study was to investigate the clinical characteristics of patients with obese asthma with positive type-2 inflammation markers. Adult obese asthmatic patients were enrolled and were classified into two groups: obese asthma with positive type-2 inflammation markers (T2) and obese asthma with negative type-2 inflammation markers (NT2), then data were compared. In total, 434 patients were enrolled (85% of patients were at GINA therapy step 4-5). The T2 group had a higher proportion of patients with persistent asthma since childhood and with allergic rhinitis. A higher percentage of patients used high-dose inhaled corticosteroids (ICS) and experienced acute exacerbations (annual exacerbation ratio ≥ 1) in the T2 group. Multivariate logistic regression analysis showed that the T2 group was independently associated with younger age, comorbidity of allergic rhinitis, persistent asthma since childhood, use of high-dose ICS, and acute exacerbation rate ≥ 1. Adipocytokine levels were similar between the groups. Collectively, obese asthma with positive type-2 inflammation markers is characterised by a higher percentage of persistent asthma since childhood and more severe asthma., (© 2023. Springer Nature Limited.)

Purpose: The prognostic significance of the cachexia index, a novel biomarker of cancer cachexia, remains unclear in colorectal cancer; we, therefore, evaluated this relationship., Methods: This retrospective cohort study included 306 patients with stage I-III colorectal cancer who underwent R0 resection between April 2010 and March 2020. The cachexia index was calculated as (skeletal muscle index [cm 2 /m 2 ] × serum albumin level [g/dL])/neutrophil-to-lymphocyte ratio. The overall and disease-free survival rates were analyzed using a Cox proportional hazards model., Results: A low cachexia index was found in 94 patients. This group had significantly lower disease-free survival and overall survival than the high-cachexia index group (5-year survival, 86.3% vs. 63.1%, p < 0.01; 87.9% vs. 67.2%, p < 0.01). Multivariate analyses showed that T3 or T4 (hazard ratio [HR]: 2.56; 95% confidence interval CI 1.04-6.25, p = 0.039), stage III (HR: 3.77; 95% CI 1.79-7.93, p < 0.01), and a low cachexia index (HR: 2.27; 95% CI 1.31-3.90, p = 0.003) were significant independent predictors of the disease-free survival. CA19-9 ≥ 37.0 ng/mL (HR: 2.68; 95% CI: 1.37-5.24, p = 0.004), stage III (HR: 2.57; 95% CI 1.34-4.92, p = 0.004), and a low cachexia index (HR: 2.35; 95% CI 1.31-4.21, p = 0.004) were significant independent predictors of the overall survival., Conclusion: A low cachexia index might be a long-term prognostic factor of colorectal cancer., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background/aim: This study aimed to identify the optimal duration of pretreatment for unresectable locally advanced (UR-LA) pancreatic cancer and analyze its effect on the prognosis., Patients and Methods: This retrospective study included 39 patients with UR-LA pancreatic cancer after pancreatectomy. The cutoff period of preoperative therapy was determined using a receiver operating characteristic curve. We investigated the relationship between preoperative and intraoperative clinical variables and overall survival (OS) in univariate and multivariate analyses. The relationship between the preoperative therapy duration and the clinicopathological variables was investigated. OS was compared according to preoperative therapy duration and the presence or absence of adjuvant surgery., Results: After pretreatment, 15 patients underwent adjuvant surgery and 24 patients continued on chemotherapy without surgery. The multivariate analysis demonstrated preoperative therapy duration ≥6 months was an independent prognostic factor [hazard ratio (HR)=0.10, p=0.04]. No significant difference in the clinicopathological variables was observed between the two groups according to preoperative therapy duration. The OS was significantly better in patients who underwent adjuvant surgery after preoperative therapy duration ≥6 months than in those after preoperative therapy duration <6 months and in those without adjuvant surgery (5-year OS rates: 80% vs. 0%; p=0.01 and 5-year OS rates: 80% vs. 0%; p=0.004, respectively). The OS was not significantly better in patients with adjuvant surgery after preoperative therapy duration <6 months than in those without adjuvant surgery (2-year OS rates: 45.7% vs. 38.1%; p=0.98)., Conclusion: Preoperative therapy for UR-LA pancreatic cancer for ≥6 months is necessary to improve prognosis after adjuvant surgery., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Systemic inflammatory response represented by C-reactive protein and albumin ratio (CAR) and modified albumin-bilirubin (mALBI) grade both have been associated with long-term outcome in patients with hepatocellular carcinoma (HCC). In this study, we investigated the prognostic utility of combined score of CAR and mALBI score to predict the prognosis of HCC patients after hepatic resection., Methods: This study included 214 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. Systemic inflammatory response and mALBI were evaluated preoperatively and patients were classified into three groups based on the combination of CAR and mALBI score: low CAR and low mALBI grade (score 0), either high CAR or high mALBI grade (score 1), and both high CAR and high mALBI grade ≥2b (score 2). Multivariate Cox proportional hazard models were conducted to assess disease-free and overall survival., Results: In multivariate analysis, sex ( p  < 0.01), HBsAg positivity ( p  < 0.01), serum AFP level ≥20 ng/mL ( p  < 0.01), microvascular invasion ( p  = 0.02), multiple tumors ( p  < 0.01), type of resection ( p  < 0.01), and CAR-mALBI score ≥2 (HR 2.19, 95% CI 1.39-3.44, p  < 0.01) were independent prognostic factors of disease-free survival, while sex ( p  = 0.01), HBsAg positivity ( p  < 0.01), poor tumor differentiation ( p  = 0.03), multiple tumors ( p  < 0.01), CAR-mALBI score ≥2 (HR 2.70, 95% CI 1.51-4.83, p  < 0.01) were independent prognostic factors of overall survival., Conclusions: CAR-mALBI score is associated with disease-free and overall survival in patients with HCC after hepatic resection, suggesting the importance of evaluating both hepatic functional reserve and host-inflammatory state in the risk assessment of HCC patients., Competing Interests: The authors declare that they have no conflicts of interest., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Objectives: The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of Fusobacterium nucleatum . We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of F. nucleatum in colorectal carcinoma., Methods: We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and KRAS , BRAF and PIK3CA mutations., Results: Fusobacterium nucleatum DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue ( P  = 0.0077). For one category-unit increase in three ordinal F. nucleatum categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28) and 0.50 (0.25-0.99), respectively ( P trend  = 0.032)., Conclusions: Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor F. nucleatum enrichment) tend to be used by different tumor subgroups., Competing Interests: ATC previously served as a consultant for Bayer Healthcare and Pfizer Inc. MG was on an advisory board for AstraZeneca and receives research funding from Bristol‐Myers Squibb. JAM has received institutional research funding from Boston Biomedical, has served as an advisor/consultant to Ignyta and COTA Healthcare, and served on a grant review panel for the National Comprehensive Cancer Network funded by Taiho Pharmaceutical. This study was not funded by any of these commercial entities., (© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Background: Identifying the prognostic indicators that reflect the efficacy of preoperative chemotherapy is necessary. In this study, we investigated the prognostic indicators targeting the systemic inflammatory response for the administration of preoperative chemotherapy in patients with colorectal liver metastases., Methods: Data for 192 patients were retrospectively analyzed. The relationship between overall survival and clinicopathological variables, including biomarkers such as the prognostic nutritional index, was investigated in patients who underwent upfront surgery or preoperative chemotherapy., Results: In the upfront surgery group, extrahepatic lesion (p=0.01) and low prognostic nutritional index (p < 0.01) were significant prognostic indicators, whereas a decrease in the prognostic nutritional index (p=0.01) during preoperative chemotherapy were independent poor prognostic factors in the preoperative chemotherapy group. In particular, a decrease in the prognostic nutritional index was a significant prognostic marker in patients aged <75 years (p=0.04). In patients with a low prognostic nutritional index aged <75 years, preoperative chemotherapy significantly prolonged overall survival (p=0.02)., Conclusion: A decrease in the prognostic nutritional index during preoperative chemotherapy predicted overall survival of patients with colorectal liver metastases after hepatic resection, and preoperative chemotherapy may be effective for patients aged <75 years with a low prognostic nutritional index., Competing Interests: Declaration of competing interest Authors declare no Conflict of Interests for this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Cholinesterase is a nutritional marker associated with sarcopenia. The present study evaluated the relationship between cholinesterase and postoperative infectious complications in patients undergoing colorectal resection for colorectal cancer., Methods: The study involved 231 patients who had undergone colorectal resection for colorectal cancer. We retrospectively investigated the relationship between preoperative serum cholinesterase levels and postoperative infectious complications. Univariate and multivariate analyses were performed to identify independent risk factors for postoperative infectious complications. We then performed stratified analyses to assess the interaction between cholinesterase and clinical variables to predict postoperative infectious complications., Results: In the multivariate analysis, the body mass index (P = 0.010), serum cholinesterase levels (P = 0.005), sarcopenia (P = 0.003) and blood loss (P < 0.001) were independent risk factors for postoperative infectious complications. In stratified analyses, the association between serum cholinesterase levels and postoperative infectious complications differed by the sarcopenia status (P interaction  = 0.006)., Conclusion: Preoperative serum cholinesterase levels may be useful for predicting postoperative infectious complications in colorectal cancer surgery. The association differs by the sarcopenia status, suggesting a potential interaction between nutritional markers and sarcopenia., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)