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Background/aim: Radiotherapy (RT) for advanced oropharyngeal cancer (OPC) is effective, especially when combined with chemotherapy (CRT). However, its success can vary depending on factors, such as tumor stage, HPV infection (p16 status), and the patient's nutritional and immune status. This study examined the controlling nutritional status (CONUT) score and tumor immunity as predictive factors for treatment outcomes in OPC, aiming to develop a personalized risk score., Patients and Methods: A retrospective analysis was conducted on 84 patients with OPC treated with definitive RT or CRT, and survival outcomes were compared based on various factors, including BMI, CONUT score, CD8 expression, and HLA class II expression., Results: We observed better overall survival (OS) rates in CD8-positive patients and those with higher HLA class II expression. The univariate analysis identified stage, p16 status, BMI, CONUT score, and CD8 expression as significantly associated with OS. In multivariate analysis, stage, BMI, and CONUT score remained significant predictors of OS. A risk scoring system was developed based on stage, p16 status, BMI, CONUT score, and CD8 expression. Patients were categorized into low-risk and high-risk groups, with significantly better survival in the low-risk group., Conclusion: A combined risk score incorporating clinical, nutritional, and immune factors can improve the prediction of treatment outcomes for OPC patients. This risk stratification may enable personalized treatment plans and improve ΟS rates., Competing Interests: The Authors declare that they have no conflicts of interest in relation to this study., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

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: 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.

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.)

Background/aim: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association., Patients and Methods: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes., Results: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS., Conclusion: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Automated measurement of immunostained samples can enable more convenient and objective prediction of treatment outcome from radiotherapy. We aimed to validate the performance of the QuPath image analysis software in immune cell markers detection by comparing QuPath cell counting results with those of physician manual cell counting., Patients and Methods: CD8- and FoxP3-stained cervical, CD8-stained oropharyngeal, and Ku70-stained prostate cancer tumor sections were analyzed in 104 cervical, 92 oropharyngeal, and 58 prostate cancer patients undergoing radiotherapy at our Institution., Results: QuPath and manual counts were highly correlated. When divided into two groups using ROC curves, the agreement between QuPath and manual counts was 89.4% for CD8 and 88.5% for FoxP3 in cervical cancer, 87.0% for CD8 in oropharyngeal cancer and 80.7% for Ku70 in prostate cancer. In cervical cancer, the high CD8 group based on QuPath counts had a better prognosis and the low CD8 group had a significantly worse prognosis [p=0.0003; 5-year overall survival (OS), 65.9% vs. 34.7%]. QuPath counts were more predictive than manual counts. Similar results were observed for FoxP3 in cervical cancer (p=0.002; 5-year OS, 62.1% vs. 33.6%) and CD8 in oropharyngeal cancer (p=0.013; 5-year OS, 80.2% vs. 47.2%). In prostate cancer, high Ku70 group had worse and low group significantly better outcome [p=0.007; 10-year progression-free survival (PFS), 56.0% vs. 93.8%]., Conclusion: QuPath showed a strong correlation with manual counting, confirming its utility and accuracy and potential applicability in clinical practice., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), 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.)

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.)

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.)

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.)

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.)

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.)

Preoperative intra-arterial chemoradiotherapy (IACRT) can improve the outcome and reduce the extent of surgery in patients with advanced oral cancer. However, the response to this regimen varies among patients, which may be related to the immune status of the tumor. We investigated the effects of proteins involved in tumor immunity on the outcomes of combined IACRT and surgery for oral cancer. We examined CD8 + and FoxP3 + tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on immune cells and tumor cells in pretreatment biopsy samples from 69 patients diagnosed with oral cancer treated with IACRT at our institution during 2000-2020. Patients with abundant CD8 + TILs had significantly better 5-year disease-specific survival (DSS) compared to that of patients with less infiltration of these cells (P = 0.016). Patients with higher FoxP3 + T-cells invasion had significantly better DSS compared to that of less FoxP3 (P = 0.005). Patients with high PD-L1 expression in tumor cells and immune cells had significantly better DSS than that of patients with low PD-L1 expression in these cells (P = 0.009 and P = 0.025, respectively). Collectively, these results suggest that the tumor immune microenvironment could affect outcomes of IACRT treatment in oral cancer., (© 2023. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Radiation can induce DNA double-stranded breaks, which are typically detected by the fluorescence of phosphorylated histone H2AX. In this study, we examined the usefulness of the dynamics of radiation-induced gamma-H2AX foci of peripheral blood lymphocytes (PBLs), as a marker of DNA repair ability, in predicting late adverse events from radiotherapy. A total of 46 patients with cervical, vaginal and anal canal cancers treated with radical radiotherapy between 2014 and 2019 were included in this analysis. Concurrent chemotherapy was administered in 36 cases (78.3%). Peripheral blood was obtained before treatment, and then irradiated ex vivo with 1 Gy X-ray. The ratio of radiation-induced gamma-H2AX foci in PBLs measured at 30 min and at 4 h was defined as the foci decay ratio (FDR). With a median follow-up of 54 months, 9 patients (19.6%) were observed to have late genitourinary or gastrointestinal (GU/GI) toxicity. The FDR ranged from 0.51 to 0.74 (median 0.59), with a significantly higher incidence of Grade 1 or higher late adverse events in the FDR ≥ 0.59 group. In multivariate analysis, FDR ≥ 0.59 and hypertension also emerged as significant factors associated with the development of late toxicities. Overall, our results suggest that measurement of radiation-induced gamma-H2AX foci in PBLs may predict the risk of late GU/GI toxicities from chemoradiotherapy, which can enable tailoring the radiation dose to minimize adverse effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background/aim: Surgical resection is recommended for nonfunctional pancreatic neuroendocrine neoplasms (NF-pNENs). However, metastasis is rare in patients with small lesions with histological grade 1 (G1); thus, observation is an optional treatment approach for small NF-pNENs. Texture analysis (TA) is an imaging analysis mode for quantification of heterogeneity by extracting quantitative parameters from images. We retrospectively evaluated the utility of TA in predicting histological grade of resected NF-pNENs in a multicenter retrospective study., Patients and Methods: The utility of TA in preoperative prediction of grade were evaluated with 29 patients treated by pancreatectomy for NF-pNEN who underwent preoperative dynamic computed tomography scan between January 1, 2013 and December 31, 2020 at three hospitals affiliated with the Jikei University School of Medicine. TA was performed with dedicated software for medical imaging processing for determining histological tumor grade using dynamic computed tomography images., Results: Histological tumor grades based on the 2017 World Health Organization Classification for Pancreatic Neuroendocrine Neoplasms were grade 1, 2 and 3 in 18, 10 and one patient, respectively. Preoperative grades by TA were 1 and 2/3 in 15 and 14 patients, respectively. The sensitivity, specificity and area under the curve for TA-oriented grade 1 lesions were 1.00, 0.889 and 0.965 (95% confidence interval=0.901-1.000), respectively., Conclusion: TA is useful for predicting grade 2/3 NF-pNEN and can provide a safe option for observation for patients with small grade 1 lesions., Competing Interests: All the Authors have no conflicts of interest to declare in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

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: Previous studies have reported that laparoscopic distal pancreatectomy (LDP) has an advantage in reducing blood loss over open distal pancreatectomy (ODP). This study was performed to investigate whether blood loss is truly reduced in LDP., Methods: A total of 113 patients undergoing DP from 2014 to 2022 were classified into Open and LDP groups and compared by statistical analysis. Estimated blood loss (EBL) was calculated from the perioperative changes in the hematocrit, hemoglobin, or red blood cell volume, and actual blood loss (ABL) was taken from the operative record., Results: ABL was significantly lower in the LDP than ODP group (50[5-1350] vs 335 [5-1950] ml, P < .01). However, there were no significant differences in EBL calculated from the hematocrit (406 [66-1990] vs 540 [23-1490] ml, P = .14), hemoglobin, or red blood cell volume. EBL showed more linear correlations with ABL in the ODP group (r = 0.64-0.73) than in the LDP group (r = 0.52-0.57). In the multivariate analysis for ABL, ODP (P = .02) and operative time (P < .01) were significant factors. In contrast, no significant factors were found for EBL., Conclusions: Intraoperative blood loss may be underestimated in LDP, and a new evaluation method needs to be established., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Aims: Immediate bleeding after cold snare polypectomy (CSP) for colorectal polyps might interfere with confirmation of residuals and prolong the time required for resection. We investigated whether submucosal epinephrine-added saline injection reduces the time required for the CSP procedure., Methods: We conducted a single-center, prospective, randomized controlled trial (clinical trial registration number: UMIN000046770). Patients with colorectal polyps ≤ 10 mm were randomly allocated to either CSP with epinephrine-added submucosal injection (CEMR group) or conventional CSP (CSP group). The primary outcome was the time required for resection defined as the time from the initiation of resection (the first insertion of the snare in the CSP group or the injection needle in the CEMR group) to the end of resection (confirming complete resection endoscopically after recognizing the cessation of immediate bleeding) in each lesion, and the secondary outcome was the time to spontaneous cessation of immediate bleeding after resection defined as the time from ensnaring the lesion to confirming the spontaneous cessation of immediate bleeding., Results: A total of 126 patients were randomly assigned. Finally, 261 lesions in 118 patients (CEMR group, n = 59; CSP group, n = 59) were analyzed. The time required for resection calculated using the least-square mean was significantly shorter in the CEMR group (106.3 s, 95% CI 97.5 to 115.4 s) than in the CSP group (130.9 s, 95% CI 121.2 to 140.7 s) (P < 0.001). The time to spontaneous cessation of immediate bleeding was also significantly shorter in the CEMR group (20.4 s, 95% CI 14.3 to 26.5 s) than in the CSP group (74.2 s, 95% CI 67.6 to 80.7 s) (P < 0.001). Neither group had cases requiring hemostasis, perforation, or delayed bleeding., Conclusions: CEMR shortened the time for resection by shortening the time to cessation of immediate bleeding compared with conventional CSP in colorectal polyps ≤ 10 mm., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Katagiri et al.)

Background: Although primary biliary cholangitis (PBC) is considered a good indication for living-donor liver transplantation (LDLT), the postoperative results are not well known., Methods: At Jikei University Hospital, 14 patients with PBC underwent LDLT from February 2007 to June 2022. We consider PBC with a Model for End-Stage Liver Disease (MELD) score of <20 to indicate LDLT. We performed a retrospective analysis of the patients' clinical records., Results: The patients' median age was 53 years, and 12 of the 14 patients were female. A right graft was used in 5 patients, and 3 ABO-incompatible transplants were performed. The living donors were children in 6 cases, partners in 4 cases, and siblings in 4 cases. The preoperative MELD scores ranged from 11 to 19 (median, 15). The graft-to-recipient weight ratio ranged from 0.8 to 1.1 (median, 1.0). The median operative time for donors and recipients was 481 and 712 minutes, respectively. The median operative blood loss of donors and recipients was 173 and 1,800 mL, respectively. The median postoperative hospital stay of donors and recipients was 10 and 28 days, respectively. All recipients recovered satisfactorily and remained well during a median follow-up of 7.3 years. Three patients underwent a liver biopsy after LDLT because of acute cellular rejection without histologic findings of PBC recurrence., Conclusions: Living-donor liver transplantation provides satisfactory long-term survival for patients with PBC with a graft-to-recipient weight ratio of >0.7 and MELD score of <20 without hepatocellular damage and only portal vein hypertension., Competing Interests: DISCLOSURES 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 Inc. All rights reserved.)

Background: The influence of fine needle aspiration (FNA) on peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) is unknown., Methods: We retrospectively analyzed 29 patients with resectable left-sided PDAC undergoing FNA prior to CY examination. We assessed clinical factors related to CY+, scored the tumor diameter (<20 mm = 0, ≥20 mm = 1) and examination interval between FNA and CY (>18 days = 0, ≤18 days = 1), and investigated the probability of CY + by the sum of each score (0-2)., Results: The probability of CY+ was 31%. The CY + group had larger tumors and shorter examination intervals than the CY- group. The CY + probability was 75%, 15%, and 13% for a score of 2, 1, and 0, respectively (P = 0.011)., Conclusion: A short interval between FNA and CY examination for a large tumor may be a risk factor for CY+ in patients with left-sided PDAC., Competing Interests: Declaration of competing interest None., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA (miRNA) expression signatures associated with the outcome of cervical cancer patients treated with CCRT. Exosomes were isolated from the plasma of 45 patients prior to CCRT during 2014-2020, and miRNA analysis was performed by next-generation sequencing. At a median follow-up of 38 months, 26 patients were recurrence free, 15 patients had died of the disease, and 4 patients received salvage chemotherapy due to distant metastasis. Of the 2522 miRNAs detected, 9 (miR-148a-5p, 1915-3p, 3960, 183-5p, 196b-5p, 200c-3p, 182-5p, 374a-5p, and 431-5p) showed differential expression between the recurrence-free and recurrence groups. Patients were divided into high- and low-risk groups according to the cutoff of the miRNAs-based risk score calculated from respective expression levels. The high-risk group had significantly worse disease-specific survival than the low-risk group (p < 0.001). In addition, miR-374a-5p and miR-431-5p expression showed a weak inverse correlation with tumor-infiltrating CD8+ and FOXP3+ T cells, suggesting a potential inhibitory effect on CCRT by suppressing tumor immunity. This miRNA signature could improve non-invasive monitoring and personalized treatment for cervical cancer., (© 2022. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Background/aim: Evidence on the optimal extent of lymph node dissection for left-sided pancreatic ductal adenocarcinoma (PDAC) is scarce. The aim of the current study was to compare the long-term outcomes of patients who underwent D1 distal pancreatectomy (DP) with D2 DP for left-sided PDAC., Patients and Methods: Patients undergoing DP for left-sided PDAC at the four institutions affiliated to The Jikei University were enrolled in this study. Patients were divided into D1 and D2 groups. Patients' clinical characteristics, overall survival (OS), and relapse-free survival (RFS) were compared between the two groups before and after propensity-score matched (PSM) analysis., Results: Of 145 patients with left-sided PDAC, 55 patients underwent D1 DP and 90 underwent D2 DP, of whom 38 matched pairs were included in the PSM analytic cohort. In the unmatched cohort, no significant difference was found between the D1 and D2 groups for both OS (median 2.51 vs. 3.07 years; p=0.709) and RFS (median 1.47 vs. 1.27 years; p=0.565). After PSM, OS (median 2.37 vs. 3.56 years; p=0.407) and RFS (median 1.35 vs. 1.11 years; p=0.542) were not significantly different between the two groups. In a comparison of regional and systemic recurrence sites, no significant difference was observed between the two groups (p=0.500)., Conclusion: The long-term survival of D1 DP for left-sided PDAC was not inferior to D2 DP. In an era in which the importance of multidisciplinary treatment for PDAC has been documented, unnecessary extended surgery should be avoided., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Factors that may make endoscopic submucosal dissection (ESD) difficult for operators have been evaluated according to results based on the performance of experienced endoscopists. This study aimed to verify the predictors of difficult gastric ESD for ESD beginners., Methods: From January 2015 to December 2021, 466 superficial gastric neoplasms were treated with ESD at Showa University Hospital. Excluding 103 lesions that performed ESD by experts who experienced more than 80 ESDs, a total of 363 lesions were included. The lesions were divided into two groups according to the ESD performance experience of the operator: ESD beginner (EB; ESD experience≤30 cases) and ESD intermediate (EI; ESD experience 31-80 cases) groups. Relationships between difficult ESD (having at least one of the following: procedure time>60 min, incomplete resection, change of operator, and occurrence of severe complications) and clinicopathological findings of the lesion were analyzed., Results: The complete resection rates and the difficult ESD rates in the EB and EI groups were 99.3%, 94.8%, and 61.2%, 50.7%, respectively. In the EB group, univariate analysis showed that difficult ESD rate was significantly higher in the non-lower third lesions, the lesser curvature lesions, and cancerous lesions. In the EI group, univariate analysis showed that difficult ESD rate was significantly higher in lesion with ≥20 mm size, lesser curvature lesions, lesions with ulcers, and submucosal cancers. Multivariate analysis showed that the lesser curvature location and cancerous histology in the EB group and ≥20 mm lesion size, the lesser curvature location and submucosal invasion in the EI group were independent predictors of difficult ESD., Conclusions: The lesser curvature location is recognized as independent ESD difficulty factor for both beginners and intermediates. Cases with lesions located in the lesser curvature should not be selected for gastric ESD training by beginners., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Higuchi et al.)

Background: Cancer cachexia has been associated with unfavorable outcomes in several malignancies. The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been proposed as a novel biomarker of cachexia. Therefore, we here investigated prognostic value of the CXI in patients with hepatocellular carcinoma (HCC) after hepatic resection., Methods: The study comprised 213 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. First, the skeletal muscle index (SMI) was calculated as the area of the psoas muscle at the third lumbar vertebra/(the height) 2 . The CXI was then calculated by the following formula: SMI x serum albumin level/neutrophil-to-lymphocyte ratio (NLR). We retrospectively investigated the relationship between the CXI and disease-free survival as well as overall survival., Results: In multivariate analyses, female (p < 0.01), hepatitis B surface antigen-positivity (p < 0.01), preoperative serum alpha-fetoprotein level ≥20 ng/mL (p = 0.01), preoperative serum protein induced by vitamin K absence or antagonist-II level ≥200 mAU/mL (p = 0.02), multiple tumors (p < 0.01), macrovascular invasion (p = 0.04), type of resection (p < 0.01), and low CXI (p = 0.03) were significant predictors of disease-free survival, while Child-Pugh grade B (p < 0.01), poor tumor differentiation (p = 0.05), multiple tumors (p = 0.01), macrovascular invasion (p = 0.04), NLR (p = 0.04), and low CXI (p < 0.01) were significant predictors of overall survival. In the subgroup analysis of advanced T stage, the CXI was associated with both disease-free (p < 0.01) and overall survival (p = 0.06)., Conclusions: The CXI can be a prognostic indicator in patients with HCC after hepatic resection, suggesting the importance of comprehensive biomarker which includes skeletal muscle, inflammation, and nutritional status., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Adjuvant chemotherapy is recommended for patients with pancreatic cancer after curative resection. However, there is limited evidence regarding the efficacy and prognostic factors for adjuvant chemotherapy in patients with stage I pancreatic cancer. This study aimed to identify patients in whom chemotherapy was effective and to detect prognostic factors for stage I pancreatic cancer based on guidelines of the 8 th edition of the Union for International Cancer Control (UICC)., Methods: Between 2009 and 2017, 108 patients diagnosed with stage I pancreatic cancer were enrolled in this study. They were distributed into invasion (n = 68) and non-invasion (n = 40) groups. The relationship between clinicopathological variables, including various prognostic factors, disease-free survival (DFS), and overall survival (OS), were investigated by univariate and multivariate analyses., Results: Five-year survival in all patients with stage I pancreatic cancer was 38.9%. Adjuvant chemotherapy failed to improve DFS or OS in patients with stage I cancer (DFS, p = 0.26; OS, p = 0.30). In subgroup analysis, adjuvant chemotherapy significantly improved DFS (multivariate-adjusted hazard ratio (HR), 0.40; 95% confidence interval [CI], 0.21-0.78; p = 0.007) and OS (multivariate-adjusted HR, 0.32; 95% CI, 0.15-0.68; p = 0.003) in the invasion group than in non-invasion group. In contrast, in the non-invasion group, adjuvant chemotherapy failed to improve DFS and OS in univariate analysis (DFS, p = 0.992; OS, p = 0.808)., Conclusion: For stage I pancreatic cancer, based on guidelines of the UICC 8 th edition, adjuvant chemotherapy may benefit patients with extrapancreatic invasion., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Combined chemoradiotherapy (CRT) and programmed cell death-ligand 1 (PD-L1) blockade is a new care standard for unresectable stage III non-small-cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy. In this study, we analyzed T-cell receptor (TCR) sequences in the peripheral blood of five patients with NSCLC. T-cell receptor analysis was undertaken before treatment, after CRT, and after PD-L1 blockade. Notably, we observed the expansion and alteration of the dominant T-cell clonotypes in all cases with a complete response. In contrast, neither expansion nor alteration of the TCR repertoire was observed in cases with progressive disease. T cell expansion was initiated after CRT and was further enhanced after PD-L1 blockade. Our findings suggest the systemic effect of CRT on circulating T cells in addition to the curative effect on limited tumor sites. Dynamic changes in circulating T-cell clonotypes could have a prognostic significance for combined CRT and PD-L1 blockade., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: Peripancreatic fluid collection (PFC) is a frequent radiological finding on postoperative computed tomography (CT) after distal pancreatectomy (DP). We evaluated the risk factors for drainage of PFC after DP to clarify the optimal management of PFC., Methods: This study included 85 patients who underwent elective DP between January 2010 and December 2020. PFC was defined as an area of fluid located at the pancreatic resection margin on postoperative routine CT on approximately postoperative day 7 (first CT). We retrospectively investigated the relationship between clinical variables, including CT findings and PFC drainage., Results: Drainage was performed in 19 patients (22.4%). Drainage for PFC was significantly associated with a longer postoperative hospital stay, higher PFC volume, presence of air bubbles, and higher white blood cell (WBC) count at the time of the first CT. According to the multivariate analyses, a PFC volume ≥ 60 mL and WBC count ≥ 12,400/μL on the day of the first CT were independent risk factors for PFC drainage after DP. The combination of these 2 factors showed 73.7% sensitivity and 90.9% specificity., Conclusion: The PFC volume and WBC count at the first CT were significantly associated with PFC drainage and may help determine the appropriate treatment., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading., Methods: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC)., Results: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC 2  = 0.870, 90% CI: 0.768-0.972)., Conclusion: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Purpose: To assess the efficacy of combination chemotherapy with nafamostat mesilate, gemcitabine and S-1 for unresectable pancreatic cancer patients., Materials and Methods: The study was conducted as a single-arm, single center, institutional review board-approved phase II trial. Patients received nafamosntat mesilate (4.8 mg/kg continuous transregional arterial infusion) with gemcitabine (1000 mg/m2 transvenous) on days 1 and15, and with oral S-1 [(80 mg/day (BSA<1.25 m2), 100 mg/day (1.25 ≤ BSA<1.5 m2), or 120 mg/day (BSA ≥1.5 m2)] on days 1-14 or, days 1-7 and 15-21. This regimen was repeated at 28-day intervals., Results: Forty-seven evaluable patients (Male/Female: 31/16, Age (median): 66 (range 35-78) yrs, Stage III/IV 10/37.) were candidates in this study. Two patients in stage III (20%) could undergo conversion surgery. Twenty-four patients (51%) underwent subsequent treatment (1st line/ 2nd line / 4th line, 13/ 10/ 1, FOLFIRINOX: 12, GEM/nab-PTX: 18, TAS-118: 3, chemoradiation with S-1: 2, GEM/Erlotinib: 1, nal-IRI: 1, surgery: 2). Median PFS and OS were 9.7 (95% CI, 8.9-14.7 mo) and 14.2 months (99% CI, 13.3-23.9 mo), respectively. Median PFS in stage IV patients was 9.2 months (95% CI, 8.4-12.0 mo). Median OS in patients without subsequent treatment was 10.8 months (95% CI, 9.1-13.8 mo). Median OS in patients with subsequent treatment was 19.3 months (95% CI, 18.9-31.9 mo). Grade 4 treatment-related hematological toxicities were encountered in 7 patients. Two patients developed grade 3 allergic reaction after 6 cycles or later. No febrile neutropenia has been observed., Conclusion: NAM/GEM/S-1 therapy is safe and could be promising option for unresectable pancreatic cancer, especially for stage IV cancer., Competing Interests: NO authors have competing interests.

Human papillomavirus (HPV)-related cancer is one of the diseases entities for which the applications of radiotherapy have been increasing. Recently, the process of carcinogenesis from HPV infection and the mechanism of tumor immunity that develops during disease progression have been elucidated. In this review, we will describe the mechanism of tumor immunity and how chemoradiotherapy may overcome and improve the efficacy of tumor immunity. We will also discuss the usefulness of proteins involved with tumor immunity as a predictive marker of radiotherapy response, and present an overview of ongoing clinical trials of combinations of immune checkpoint inhibitors and radiotherapy to demonstrate the promising combination therapy that has been currently emerging., (© 2021. The Author(s).)

To evaluate omega-3 fatty acid-rich enteral nutrient effects in patients with unresectable or recurrent biliary tract or pancreatic cancers during chemotherapy. Enteric nutritional supplements containing omega-3 fatty acids (Racol ® ) was administered to aforementioned patients with cancers during chemotherapy. The skeletal muscle mass and blood test data were obtained pre-administration and 28 and 56 days after. Patients with pancreatic cancer were administered the digestive enzyme supplement pancrelipase (LipaCreon ® ) 28 days after the start of Racol ® administration. The number of chemotherapies skipped due to neutropenia was recorded for 2 months before and after enteral nutrient initiation. In all 39 patients, the skeletal muscle mass increased on day 56 versus baseline (median 17.3 kg vs. 14.8 kg, p < 0.01), number of chemotherapies skipped decreased (mean: 0.65 times/month vs. 1.3 times/month, p = 0.03), and retinol-binding protein (mean: 2.56 mg/dL vs. 2.42 mg/dL, p = 0.05) increased. Patients with pancreatic cancer showed increased blood eicosapentaenoic acid concentration on day 56 versus baseline (median: 48.1 μg/mL vs. 37.0 μg/mL, p = 0.04) and increased skeletal muscle mass (median 16.8 kg vs. 14.4 kg, p = 0.006). Baseline median neutrophil count increased significantly from 2200/μL at baseline to 2500/μL (p = 0.04). Patients with biliary tract cancer during chemotherapy also exhibited increased skeletal muscle mass following omega-3 supplementation (median 17.3 kg vs. 15.8 kg, p = 0.01). In patients undergoing chemotherapy for unresectable or post-recurrence pancreatic and biliary tract cancers, high-omega-3 fatty acid nutrition therapy use improved skeletal muscle maintenance and chemotherapy dosing intensity., (© 2022. The Author(s).)

Background: To study exocrine function of the remnant pancreas after pancreatoduodenectomy (PD), we propose the use of an exocrine index (PEI) that combines the volume of the remnant pancreas and the intraoperative amylase activity of the pancreatic juice. Here, we aimed to determine whether the PEI can predict non-alcoholic fatty liver disease (NAFLD) following PD., Methods: Fifty-seven patients for whom pancreatic juice amylase activity was measured during PD were enrolled. NAFLD was defined as a liver-to-spleen attenuation ratio of <0.9 on plain CT 1 year following surgery. We retrospectively evaluated clinical parameters, including the PEI, to identify predictors of NAFLD., Results: Fifty-four patients (95%) were regularly administered 1200 mg of pancreatic lipase. NAFLD was diagnosed in 13 participants (23%) 1 year following surgery. NAFLD was associated with pancreatic ductal adenocarcinoma ( P  = .006), soft pancreas ( P  = .001), small main pancreatic duct ( P  = 0008), low remnant pancreatic volume ( P  < .001), low intraoperative amylase activity in the pancreatic juice ( P  = .001), high pancreatic fibrosis ( P  = .032), and large body weight loss ( P  = .015). The PEI was significantly lower in the participants with NAFLD than in those without ( P  < .001). The participants were then classified into tertiles of PEI: <5 × 10 6 , 5-25 × 10 6 , and >25 × 10 6 . The prevalence of NAFLD in these groups was 53% (10/19), 11% (2/19), and 5% (1/19), respectively. In multivariable analyses, there was a significant association between NAFLD and the PEI ( P value for trend = .042)., Conclusion: The PEI, calculated using the remnant pancreatic volume and the intraoperative pancreatic juice amylase activity, predicts NAFLD development following PD., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

The patient was a 61-year-old woman with a history of diabetes mellitus who had undergone ileocecal resection for ascending colon carcinoma 5 years earlier, followed by a postoperative adjuvant chemotherapy with XELOX (capecitabine + oxaliplatin). During follow-up, the liver gradually atrophied, and radiological imaging showed suspicious findings of 20 × 14 mm hepatocellular carcinoma (HCC) in the right lobe of the liver. The patient also underwent endoscopic variceal ligation for the esophageal varices. She was referred to our hospital for living donor liver transplantation (LDLT) due to decompensated liver cirrhosis with HCC. The patient did not have hepatitis B or C, and history of alcohol, suggesting that her liver cirrhosis was caused by a non-alcoholic steatohepatitis. The Child-Pugh score was 10 points (class C) and the Model for End-Stage Liver Disease (MELD) score was 8 points. The possibility of HCC could not be ruled out, and LDLT was performed. Postoperative pathological examination revealed idiopathic portal hypertension (IPH), and the mass lesion was diagnosed as focal nodular hyperplasia (FNH). The postoperative course was uneventful and the patient was discharged on postoperative day 14. This is the first case of liver transplantation for IPH with FNH., (© 2022. The Author(s).)

Background: Undifferentiated carcinoma with osteoclast-like giant cells (UCOGCs) is a rare subtype of pancreatic cancer (PC), and its clinicopathological characteristics are still unclear. Herein, we report a case of initially unresectable UCOGC that was successfully resected after FOLFIRINOX therapy., Case Presentation: A 63-year-old man was referred to us for evaluation of a pancreatic mass detected by computed tomography (CT) during a medical checkup. Computed tomography showed a 7.5-cm tumor located in the pancreatic head and body, which involved the common hepatic artery (CHA), gastroduodenal artery (GDA), and main portal vein (PV) with tumor thrombus. UCOGC was suspected by endoscopic ultrasonography-guided fine needle aspiration, and the patient was diagnosed with unresectable locally advanced pancreatic cancer. After ten cycles of FOLFIRINOX, the tumor size decreased to 3 cm and the tumor thrombus in the main portal trunk had disappeared in the follow-up CT scan. However, the patient experienced severe adverse drug reactions, including neutropenia and liver dysfunction. Therefore, we performed pancreatoduodenectomy with portal vein resection. The pathological diagnosis was UCOGC with a negative tumor margin. He was treated with FOLFIRINOX, and remains recurrence-free for 6 months after surgery., Conclusions: We experienced a case undergoing conversion surgery for unresectable UCOGC, which resulted in R0 resection. FOLFIRINOX could be a possible regimen to achieve conversion surgery for UCOGC., (© 2022. The Author(s).)

Background: Acute pancreatitis could be an early symptom of pancreatic cancer. However, repeated pancreatitis caused by pancreatic cancer is very rare., Case Presentation: A 69-year-old man was referred to our hospital with severe abdominal pain, and serial imaging studies showed acute distally localized pancreatitis with a pseudocyst. Although he had successful conservative medical treatment followed by discharge from the hospital, he was re-admitted with severe abdominal pain for recurrent distal pancreatitis with splenic artery aneurysm followed by its rupture. No pancreas mass was detected by imaging studies including endoscopic ultrasound and cytologic studies of the pancreas juice did not show any malignant cells, although slight dilatation of distal pancreas duct was observed only in the initial computed tomography. Because of the episodes of repeated distally localized pancreatitis caused by possible pancreatic ductal neoplasm, we planned and performed laparoscopy-assisted distal pancreatectomy after full-informed consent. Pathological examination revealed pancreatic intraepithelial neoplasia (PanIN) with carcinoma in situ in the distal main pancreas duct. The post-surgical course of the patient was uneventful and he was discharged 10 days after surgery from recurrent disease for over a year., Conclusions: We encountered a case of repeated episodes of acute distally localized pancreatitis, for which distal pancreatectomy was performed, resulting in pathological diagnosis of PanIN with carcinoma in situ., (© 2022. The Author(s).)

Background: The administration of direct-acting antiviral agents in patients with liver cirrhosis and hepatitis C has been shown to improve liver function and long-term prognosis after sustained virological response (SVR) is achieved. However, in patients with portal hypertension (PH) at the time of SVR, PH may persist despite improvement in liver function., Case Presentation: An 82-year-old woman with liver cirrhosis due to hepatitis C was treated with direct-acting antiviral agents and achieved SVR. During follow-up, computed tomography revealed a low-density tumor in the left lateral region of the liver with dilation of the left intrahepatic bile duct. Considering the patient's advanced age and PH persistence with a mild decrease in liver reserve function after SVR, preoperative percutaneous transhepatic portal embolization (PTPE) and partial splenic embolization (PSE) were performed concomitantly. Laparoscopic left hemihepatectomy was performed 8 days after the PTPE and PSE. The patient was discharged 8 days after surgery without any postoperative complications., Conclusions: Laparoscopic left hemihepatectomy after preoperative management of PH was performed safely in a patient after the elimination of hepatitis C., (© 2021. The Author(s).)

Background: Nutritional status assessment is essential in cancer patients because a poor nutritional status has been associated with poor outcomes; however, the impact of rapid turnover proteins (RTPs), such as prealbumin, transferrin, and retinol-binding protein, on the outcomes of hepatocellular carcinoma (HCC) has not been well-investigated. We therefore examined the prognostic significance of RTPs in patients with HCC after curative resection., Methods: This study included 150 patients who underwent elective hepatic resection for HCC between January 2011 and December 2018. The prealbumin, transferrin, and retinol-binding protein levels were classified into two groups (high vs. low); the RTP score (0-3) was calculated as the sum of each RTP measurement (high = 0; low = 1). We retrospectively investigated the relationship between the RTP score and disease-free and overall survival., Results: Multivariate analysis showed that a high RTP score (P = 0.022), presence of sarcopenia (P = 0.001), and stage III or higher (P = 0.005) were independent predictors of disease-free survival, while a high RTP score (P < 0.001), presence of sarcopenia (P = 0.017), and stage III or higher (P = 0.012) were independent predictors of overall survival. In patients with high RTP scores, positive hepatitis B and C viral infection, high indocyanine green (ICG) at 15 min (ICG R15 ), Child-Pugh grade B, poorly differentiated carcinoma, and postoperative ascites were more common than in patients with low RTP scores., Conclusion: The preoperative RTP score may be a prognostic factor in patients with hepatocellular carcinoma after hepatic resection, suggesting an important role of RTP in the assessment of nutritional status in cancer patients., (© 2021. Society of Surgical Oncology.)

Background: The superiority of outcomes associated with anatomical resection (AR) versus those associated with non-anatomical resection (NAR) remains controversial in patients with hepatocellular carcinoma (HCC). The aim of this study was to evaluate the significance of AR on therapeutic outcomes of patients with small HCCs (≤ 5 cm), using propensity score-matched (PSM) analysis., Methods: A total of 195 patients who had undergone elective hepatic resection for small HCCs (≤ 5 cm) were included in this study. We conducted PSM analysis for baseline characteristics (age, sex, hepatitis virus status, retention rate of indocyanine green at 15 min, and Child-Pugh grade), preoperative serum α-fetoprotein, and tumor characteristics (tumor size, tumor number, portal vein invasion, and surgical margin status) to eliminate potential selection bias. The prognostic significance of AR on the disease-free and overall survival was analyzed in patients selected by PSM analysis., Results: Applying PSM analysis, the patients were divided into PSM-AR (N = 66) and PSM-NAR (N = 66) groups. Disease-free survival was significantly better in the PSM-AR group than that of the PSM-NAR group (P = 0.018), while there was no significant difference in the overall survival between the PSM-AR and PSM-NAR groups (P = 0.292). The univariate HRs of the PSM-AR group were 0.55 (95% CI, 0.33-0.90) for disease-free survival and 0.61 (95% CI, 0.24-1.53) for overall survival, respectively. Remnant liver recurrence was significantly lower in the AR group (P = 0.014)., Conclusions: AR may improve the disease-free survival in HCC patients with tumors of ≤5 cm diameter., (© 2021. The Society for Surgery of the Alimentary Tract.)

A hepatic cone-unit represents an anatomical unit dominated by a smaller Glissonean pedicle. Anatomical resection of a tumor located in an intersegmental plane is challenging, but could be achieved effectively by performing multiple cone-unit resection. We performed double cone-unit laparoscopic resection of hepatocellular carcinoma located on the intersegmental plane between segments 6a, b. The liver parenchyma covering the posterior Glissonean pedicle was divided along Rouviere's sulcus, the Glissonean branches of segments 6a, b were isolated and ligated, and indocyanine green (ICG) negative counterstaining was performed. The hepatic parenchyma was dissected along the demarcation line to identify the right hepatic vein and the double cone-unit resection was then completed with a negative surgical margin. Thus, double cone-unit laparoscopic hepatectomy with ICG negative counterstaining may be a feasible option for tumors located in an intersegmental plane., (© 2021. Springer Nature Singapore Pte Ltd.)

Background/aim: The aim of this study was to investigate the risk factors of surgical site infection (SSI) in patients who underwent liver resection for colorectal liver metastases (CRLM)., Patients and Methods: A total of 151 patients who underwent liver resection for CRLM were included in this study. We investigated the relationship between the patient characteristics and perioperative factors and the incidence of SSI., Results: Nineteen (13%) of these patients developed SSI. Multivariate analysis revealed that modified Glasgow Prognostic Score (mGPS) (1 or 2, odds ratio 3.86, p=0.03) and presence of an enterostomy (yes, odds ratio 3.93, p=0.04) were significant and independent risk factors for SSI., Conclusion: A higher mGPS and an enterostomy were risk factors for SSI in patients who underwent a liver resection for CRLM., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Several kinds of systemic inflammatory response, classified into two types: C-reactive protein (CRP)-based type and blood cell count-based type, were reported as a prognostic indicator in patients with pancreatic cancer (PC). However, there is no consensus which types is more sensitive predictor in patients with PC. Therefore, we here developed a novel biomarker, C-NLR, which consists of both CRP and neutrophil-to-lymphocyte ratio (NLR), and we evaluated the prognostic significance of C-NLR in patients with PC after pancreatic resection., Methods: A total of 217 patients was comprised in this study. We retrospectively investigated the relation between C-NLR and disease-free survival (DFS) and overall survival (OS) after pancreatic resection., Results: Optimal cutoff level of C-NLR was defined as 0.206 by a ROC analysis. By multivariate analysis, age (P = 0.024), TNM stage (P < 0.001), and C-NLR (HR: 1.373, 95% CI: 1.005-1.874, P = 0.046) were independent predictors of DFS, whereas TNM stage (P = 0.016) and C-NLR (HR: 1.468, 95% CI: 1.042-2.067, P = 0.028) were independent predictors of OS., Conclusion: Preoperative C-NLR can be a prognostic indicator in patients with PC after pancreatic resection, suggesting the importance of both CRP and blood cell count in predicting therapeutic outcomes., (© 2021. Japan Society of Clinical Oncology.)

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach., Methods/design: Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival., Discussion: If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view., Trial Registration: UMIN Clinical Trials Registry UMIN000041381 . Registered on 10 August 2020. ClinicalTrials.gov NCT04600063 . Registered on 22 October 2020., (© 2021. The Author(s).)

It has been known that repeat laparoscopic hepatectomy (RLH) after open hepatectomy is technically challenging because of adhesions around the hilum. It is quite often that conventional tourniquet technique for the Pringle maneuver is difficult in RLH, and we introduced Laparoscopic Satinsky Vascular Clamp (LSVC) for inflow control in RLH. The Spiegel lobe is the anatomical landmark in LSVC technique. If a space behind the hepatoduodenal ligament and the Spiegel lobe was obtained, LSVC was applied laterally from the left side of the hepatoduodenal ligament, whereas LSVC was vertically applied for those with obstruction of a space behind the hepatoduodenal ligament. We performed 14 cases of RLH for those with histories of open hepatectomies by lateral (n = 6) and vertical (n = 8) LSVC technique with successful inflow control, confirmed by intraoperative Doppler ultrasound. Five patients underwent 2 or more previous histories of hepatectomies. The RLH included segmentectomy (n = 1), subsegmentectomy (n = 2) and partial hepatectomy (n = 11). The median time for the Pringle maneuver, operative time, and blood loss was 47 min, 237.5 min, and 160 mL. All the patients completed pure laparoscopic hepatectomy. In conclusion, LSVC technique is a safe and reliable technique for the Pringle maneuver in RLH., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer., (© 2021. The Japanese Society for Clinical Molecular Morphology.)