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We describe the case of a 70-year-old Japanese man with familial amyotrophic lateral sclerosis (fALS) associated with a p.Gly93Ser mutation in the copper/zinc superoxide dismutase (SOD1) gene. This mutation is one of the relatively rare SOD1 mutations, with only one previous autopsy report, and is known for its longer disease duration. As previously reported, the patient had weakness in the lower limbs at age 33, followed by dysphagia, dysesthesia in the lower limbs, and autonomic dysfunction. He required mechanical ventilation at age 44 and died of acute pancreatitis at age 70. Neuropathologically, multisystem degeneration was observed beyond lesions typical of familial ALS with posterior column involvement. In addition, there was no SOD1-positive inclusion in the remaining motor neurons. The absence of SOD1-positive inclusion is a rare feature observed predominantly in long survival cases with SOD1 gene mutations. We hypothesize that the considerably lower amount of abnormal SOD1 protein in the motor neuron cells might explain our patient's extraordinarily long clinical course., (© 2024 Japanese Society of Neuropathology.)

Background/aim: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin that is frequently associated with anorectal carcinoma. Rectal canal carcinoma with Pagetoid spread (PS) is a relatively rare disease, and few reports on its outcomes are available. The relatively rare nature of this disease makes the development of treatment recommendations difficult. This study aimed to clarify the characteristics of the disease and factors related to prognosis. We present a case report and review of 89 cases, including those from the existing literature and our own experience., Case Report: The patient was an 81-year-old man who was referred to our hospital for surgery after endoscopic examination of the lower gastrointestinal tract revealed cancer of the anal canal with PS. Physical examination revealed erythema and erosions around the anus. Lower gastrointestinal endoscopy revealed an erythematous area and a continuous raised lesion in the anal canal. We diagnosed the patient with anal canal carcinoma with PS, and robot-assisted abdominoperineal resection was performed., Conclusion: Our findings indicate that the five-year survival rate for PPD patients was 63%, comparable to that of anal canal cancer without PS. The histological type and presence of lymph node metastasis may be related to the prognosis. The study suggests that early-stage patients with favorable histological types and no lymph node involvement may benefit from less invasive treatment options, such as endoscopic submucosal dissection., Competing Interests: The Authors declare no conflicts of interest in relation to this study., (©2025 The Author(s). Published by the International Institute of Anticancer Research.)

Introduction: The prognostic nutritional index (PNI) and D-dimer level are two useful measures for gastric cancer prognosis. As they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a PNI-D score - which combines the PNI and D-dimer level - and validate its usefulness as a prognostic marker., Methods: We collected data from 1,218 patients with gastric cancer who had undergone radical gastrectomy (R0) between January 2004 and December 2015. Patients were divided into three PNI-D score groups based on the following criteria: score 2, low-PNI (≤46) and high D-dimer levels (>1.0 µg/mL); score 1, either low-PNI or high D-dimer levels; and score 0, no abnormality. We defined the PNI-D score as low (score 0 or 1) and high (score 2), respectively., Results: The PNI-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank p < 0.0001). The 5-year overall survival rates of patients with PNI-D scores of low and high were 88.1% and 64.7%, respectively; their 5-year recurrence-free survival rates were 86.7% and 61.3%, respectively; and their 5-year disease-specific survival rates were 99.3% and 76.5%, respectively. Cox multivariate analysis revealed that a high-PNI-D score was an independent, statistically significant prognostic factor for poor overall (p = 0.01) survival in patients with gastric cancer., Conclusions: The PNI-D is an independent prognostic factor for patients with gastric cancer., (© 2024 S. Karger AG, Basel.)

Prostate cancer (PCa) is a heterogeneous disease that exhibits androgen sensitivity and responsiveness to androgen deprivation therapy (ADT). However, ADT induces only temporary remission, and the majority of PCa cases eventually progress to castration-resistant PCa (CRPC). During the development and progression of CRPC, androgen sensitivity and androgen receptor (AR) dependency in PCa cells are often deceased or lost due to ADT or spontaneously arising AR variants even before starting ADT. To prevent CRPC, a clinical PCa model derived from an AR-positive cancer cell line with weak or no androgen sensitivity is required. The human prostate LNCaP cell line is a good model for PCa because of its androgen sensitivity and AR dependency in terms of cell growth and gene expression. Notably, LNCaP cells are heterogeneous cells comprising different clones with natural variations in androgen sensitivity and AR dependency resulting from spontaneously occurring changes. In our group, to obtain androgen-insensitive or weakly sensitive clones spontaneously derived from parental LNCaP cells, we performed a limiting dilution of parental LNCaP cells and obtained several sublines with varying levels of androgen sensitivity and AR dependency. In addition, we established an androgen-insensitive subline from parental LNCaP cells by continuous passage under hormone-depleted conditions. This article provides a unique perspective on our original PCa progression model interacting with fibroblasts and its application in preclinical research.

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m 2 ) on day 1 and two divided doses oral capecitabine (2000 mg/m 2 /day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer., (© 2024. The Author(s).)

Malignant lymphoma is a relatively rare complication in patients with ulcerative colitis (UC) and its etiology is unclear. We present a hard-to-diagnose case of Epstein-Barr virus-positive diffuse large B-cell lymphoma in an elderly patient with UC who was treated with the immunomodulator tacrolimus and herbal medicine including indigo naturalis. Because malignant lymphomas can mimic other inflammatory diseases macroscopically, diagnosis in such cases can be challenging., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Review Board of Osaka International Medical & Science Center issued approval NA. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: T.M. received lecture fee from Takeda and was affiliated with an endowed chair from Kinshukai Medical Corp. The other authors declare no conflict of interest. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hamamoto et al.)

Background: The short-term outcomes of chemoradiotherapy (CRT) with S-1 (a combination of tegafur, gimeracil, and oteracil) following limited surgery for patients with T1 or T2 lower rectal cancer have shown encouraging results., Objectives: This study was designed to delve deeper into the long-term outcomes of CRT with S-1 after limited surgery, with the goal of evaluating both the long-term efficacy and potential risks associated with this treatment approach in patients diagnosed with T1 or T2 lower rectal cancer., Methods: This was conducted as a multicenter, single-arm, prospective phase II trial. The patient population consisted of individuals clinically diagnosed with either T1 or T2 lower rectal or anal canal cancer, with a maximum tumor diameter of 30 mm and classified as N0 or M0. Patients underwent local excision or endoscopic resection. After surgery, CRT with S-1 was administered to patients meeting several criteria, including the confirmation of well-differentiated or moderately differentiated adenocarcinoma, negative surgical margins, submucosal invasion depth of ≥1000 µm, and high tumor-budding grade (2/3). The primary endpoint of this study was relapse-free survival, while secondary endpoints included local recurrence-free survival, overall survival, anal sphincter preservation rate, and safety., Results: A total of 52 patients were included, with pathological diagnoses revealing T1 in 36 patients and T2 in 16 patients. The 3-year and 5-year relapse-free survival rates were 90.17% and 85.87%, respectively. The 3-year and 5-year local recurrence-free survival rates were 90.17% and 88.07%, respectively, while the 3-year and 5-year overall survival rates were 94.03% and 91.94%, respectively., Conclusions: CRT with S-1 after limited surgery for T1 lower rectal cancer demonstrated favorable outcomes in terms of recurrence, survival, and local control rates while effectively maintaining anal function in patients. However, further treatment approaches may be necessary to improve outcomes for patients diagnosed with stage T2 lower rectal cancer.

Background & Aims: This study aimed to investigate the temporal changes in body composition following esophagectomy in patients with esophageal cancer using bioelectrical impedance analysis and to assess the prognostic implications of these changes., Methods: Our study included 528 patients who underwent esophagectomy and preoperative body composition measurements between January 2013 and June 2020. Postoperative body composition was measured in 493 patients at discharge as follows: 184 at 1 month, 144 at 2 months, 143 at 3 months, 103 at 6 months, 58 at 9 months, and 78 at 12 months., Results: Body weight (BW) continuously decreased until the 6 postoperative months (POMs), reaching -11.5% compared with preoperative levels. Subsequently, almost no change was observed at 12 POMs. Skeletal muscle mass (SMM) decreased until 3 POMs but gradually recovered after 3 POMs. Conversely, body fat mass (BFM) consistently decreased over time post-esophagectomy. The patients were categorized into moderate (>-10%) and severe (≤-10%) groups based on % BW, % SMM, and % BFM losses at 3 POMs. Severe SMM loss at 3 POMs correlated with reduced overall survival (OS) (3-year OS: 85.9% in moderate vs. 75.1% in severe, p = 0.035). BFM loss was associated with reduced recurrence-free survival (3-year RFS: 83.3% in moderate vs. 62.0% in severe, p = 0.011). Multivariate analysis identified pStages Ⅲ and Ⅳ, % SMM loss ≤ -10%, and % BFM loss ≤ -10% as independent factors for worse OS., Conclusion: Post-esophagectomy, distinct temporal changes in BW, SMM, and BFM are observed. Significant reductions in SMM and BFM 3 POMs indicate a poor long-term prognosis., Competing Interests: Conflict of interest Authors declare no conflict of interests for this article., (Copyright © 2024. Published by Elsevier Ltd.)

We synthesized ridaifen-B boron dipyrromethene ( RID-B-BODIPY ) using 2-methyl-6-nitro benzoic anhydride (MNBA)-mediated dehydration condensation reaction between amino alkyl-tethered RID and BODIPY FL. Comparative experiments between dicyclohexylcarbodiimide (DCC) and MNBA for their coupling reactions demonstrated that MNBA is an effective condensation reagent for amines and BODIPY FL. A cell staining study with RID-B-BODIPY showed intracellular localization of BODIPY FL fluorescence, attributed to the RID-B structure, indicating the successful development of a tool for analyzing intracellular molecular behavior efficiently., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Murata, Komukai, Semba, Murata, Sato, Takano, Tsuchiya, Matsuda, Sakai, Yoneoka, Takahashi, Nagahara and Shiina.)

Background: Advanced hepatobiliary-pancreatic cancer often invades critical blood vessels, including the portal vein (PV) and hepatic artery. Resection with tumor-free resection margins is crucial to achieving a favorable prognosis in these patients. Herein, we present our cases and surgical techniques for PV wedge resection with patch venoplasty using autologous vein grafts during surgery for pancreatic ductal adenocarcinoma (PDAC) and perihilar cholangiocarcinoma (PhCC)., Case Presentation: Case 1: 73-year-old female patient with PDAC; underwent subtotal stomach-preserving pancreatoduodenectomy, with superior mesenteric vein wedge resection and venoplasty with the right gonadal vein. Case 2: 67-year-old male patient with PDAC; underwent distal pancreatectomy and celiac axis resection, with PV wedge resection and venoplasty with the middle colic vein. Case 3: 51-year-old female patient with type IV PhCC; underwent left hepatectomy with caudate lobectomy and bile duct resection, with hilar PV wedge resection and venoplasty with the inferior mesenteric vein (IMV). Case 4: 69-year-old male patient with type IIIA PhCC; underwent right hepatopancreatoduodenectomy, with hilar PV resection and patch venoplasty with the IMV. All patients survived for over 12 months after the surgery, without local recurrence., Conclusions: PV wedge resection and patch venoplasty is a useful technique for obtaining tumor-free margins in surgeries for hepatobiliary-pancreatic cancer., (© 2024. The Author(s).)

Introduction: Curative esophagectomy is not always possible in patients with locally advanced esophageal cancer. However, few studies have investigated patients who underwent non-curative surgery with intraoperative judgment. This study aimed to investigate patient characteristics and clinical outcomes for patients undergoing non-curative surgery and compare them between non-resectional and non-radical surgery., Methods: Among 989 consecutive patients with thoracic esophageal squamous cell carcinoma who were preoperatively expected for curative esophagectomy, 66 who were eligible for non-curative surgery were included in this study., Results: Intraoperative diagnosis of T4b accounted for 93% of the reasons for the failure of curative surgery. In those patients, esophageal cancer locally invaded into the aortobronchial constriction (70%), trachea (25%), or pulmonary vein (5%). Lymph node metastasis mainly invaded into the trachea (50%) or bronchus (28%). The overall survival of patients with non-curative surgery was 51.5%, 25.7%, and 10.4% at 6, 12, and 24 months after surgery, respectively. Although there were no differences in preoperative patient characteristics between non-resectional and non-radical surgery, distant metastasis, especially pleural dissemination, was significantly observed in T4b patients due to esophageal cancer with non-radical surgery than those with non-resectional surgery (35% vs. 15%, p = 0.002). Even in patients with non-curative surgery, R1 resection and postoperative chemoradiotherapy were identified as independent factors for survival 1 year after surgery (p = 0.047, and 0.019)., Conclusions: T4b tumor located in aortobronchial constriction or trachea/bronchus makes it difficult to diagnose whether it is resectable or unresectable. Moreover, surgical procedures and perioperative treatment were deeply associated with the clinical outcomes., (© 2023 S. Karger AG, Basel.)

Objective: To investigate somatosensory pathway function in patients with amyotrophic lateral sclerosis (ALS) dependent on invasive ventilation and in a completely locked-in state (CLIS)., Methods: We examined median nerve somatosensory evoked potentials (SEPs) in 17 ALS patients in a CLIS, including 11 patients with sporadic ALS, one with familial ALS with genes not examined, four with a Cu/Zn superoxide-dismutase-1 (SOD1) gene variant (Val118Leu, Gly93Ser, Cys146Arg), and one with a fused-in-sarcoma gene variant (P525L). We evaluated N9, N13, N20 and P25, and central conduction time (CCT); the data were compared with those of 73 healthy controls., Results: N20 and N13 were abolished in 12 and 10 patients, and their latencies was prolonged in four and three patients, respectively. The CCT was prolonged in five patients with measurable N13 and N20. Two patients with SOD1 gene mutations had absent or slightly visible N9. Compared to the CCT and latencies and amplitudes of N13 and N20 in the controls, those in the patient cohort were significantly abnormal., Conclusions: The central somatosensory pathway is severely involved in patients with ALS in a CLIS., Significance: Our findings suggest that median nerve SEP cannot be utilized for communication in patients with ALS in a CLIS., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Circulating tumor cells (CTCs) play an important role in metastasis and recurrence. However, which cells comprise the complex tumor lineages in recurrence and are key in metastasis are unknown in colorectal cancer (CRC). CRC with high expression of POU5F1 has a poor prognosis with a high incidence of liver metastatic recurrence. We aim to reveal the key cells promoting metastasis and identify treatment-resistant lineages with established EGFP-expressing organoids in two-dimensional culture (2DOs) under the POU5F1 promotor. POU5F1-expressing cells are highly present in relapsed clinical patients' blood as CTCs. Sorted POU5F1-expressing cells from 2DOs have cancer stem cell abilities and abundantly form liver metastases in vivo. Single-cell RNA sequencing of 2DOs identifies heterogeneous populations derived from POU5F1-expressing cells and the Wnt signaling pathway is enriched in POU5F1-expressing cells. Characteristic high expression of CTLA4 is observed in POU5F1-expressing cells and immunocytochemistry confirms the co-expression of POU5F1 and CTLA4. Demethylation in some CpG islands at the transcriptional start sites of POU5F1 and CTLA4 is observed. The Wnt/β-catenin pathway inhibitor, XAV939, prevents the adhesion and survival of POU5F1-expressing cells in vitro. Early administration of XAV939 also completely inhibits liver metastasis induced by POU5F1-positive cells., (© 2023. The Author(s).)

Background/aim: The Japanese Gastric Cancer Treatment Guidelines recommend doublet chemotherapy (S-1 plus another chemotherapy) over S-1 alone for patients with pStage III gastric cancer who underwent radical gastrectomy. However, no consensus exists on adjuvant regimens for patients with pStage III gastric cancer. Therefore, we conducted a comparative study to evaluate the tolerability, safety, and survival outcomes of docetaxel plus S-1 (DS) and S-1 plus oxaliplatin (SOX) therapies as adjuvant chemotherapy for patients with pStage III gastric cancer., Patients and Methods: We retrospectively collected data from consecutive patients with gastric cancer who underwent gastrectomy and received DS or SOX therapies postoperatively at the Osaka International Cancer Institute between December 2016 and December 2021. We conducted a propensity score matching analysis to balance clinical backgrounds., Results: Eighty patients who met the eligibility criteria were analyzed. After matching, 40 patients were included in the study (20 each in the DS and SOX groups). No significant adverse events were observed. The mean ratios of the delivered dose to the planned dose were 74.1% and 86.6% for S-1 and docetaxel in the DS group, respectively, and 75.8% and 76.9% for S-1 and oxaliplatin in the SOX group, respectively. No significant differences were found in recurrence-free and overall survival between the DS and SOX groups (p=0.688 and p=0.772, respectively)., Conclusion: DS and SOX therapies as adjuvants were safe and manageable for patients with pStage III gastric cancer who underwent radical gastrectomy. No significant differences were found in prognosis between the two therapies., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: DNA integrity number (DIN) is a metric for assessing DNA degradation, calculated based on electrophoresis using the Agilent TapeStation System. The utility of DIN as a diagnostic indicator of sufficient DNA quality in clinical next-generation sequencing (NGS) has not been well described., Methods: We evaluated the DINs of 166 tumor formalin-fixed, paraffin-embedded (FFPE) tissue samples submitted for 124-gene panel sequencing. We also investigated a new metric on the electropherogram that could improve the predictive accuracy of the DIN., Results: A DIN cutoff of 2.5 discriminated samples with successful analysis (n = 143) from samples with failed analysis (n = 23), with a sensitivity of 0.84 and a specificity of 0.78 (area under the curve [AUC] = 0.88). The DIN was positively correlated with the mean coverage (r = 0.72, P < .0001) but could not discriminate success from failure when the DIN was below 2.5 (negative predictive value, 0.44). We introduced a new metric, the peak/base ratio, that distinguished success from failure with higher accuracy than the DIN (cutoff = 1.6; sensitivity = 0.98, specificity = 0.83, and AUC =0.96)., Conclusions: To predict successful NGS, the DNA quality of FFPE tissue can be easily and reliably assessed using the DIN and peak/base ratio., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pancreatic ductal adenocarcinoma (PDAC) is the cancer with the poorest prognosis. One of the major properties reflecting its poor prognosis is high-grade heterogeneity, which leads to insensitivity to anticancer treatments. Cancer stem cells (CSCs) acquire phenotypic heterogeneity, generating abnormally differentiated cells by asymmetric cell division. However, the detailed mechanism leading to phenotypic heterogeneity is largely unknown. Here, we showed that PDAC patients with co-upregulation of PKCλ and ALDH1A3 had the poorest clinical outcome. PKCλ knockdown by DsiRNA in the ALDH1 high population of PDAC MIA-PaCa-2 cells attenuated the asymmetric distribution of the ALDH1A3 protein. To monitor asymmetric cell division of ALDH1A3-positive PDAC CSCs, we established stable Panc-1 PDAC clones expressing ALDH1A3-turboGFP (Panc-1-ALDH1A3-turboGFP cells). In addition to MIA-PaCa-2-ALDH1 high cells, turboGFP high cells sorted from Panc-1-ALDH1A3-turboGFP cells showed asymmetric cell propagation of ALDH1A3 protein. PKCλ DsiRNA in Panc-1-ALDH1A3-turboGFP cells also attenuated the asymmetric distribution of ALDH1A3 protein. These results suggest that PKCλ regulates the asymmetric cell division of ALDH1A3-positive PDAC CSCs. Furthermore, Panc-1-ALDH1A3-turboGFP cells can be useful for the visualization and monitoring of CSC properties such as asymmetric cell division of ALDH1A3-positive PDAC CSCs in time-lapse imaging., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Androgen deprivation therapy (ADT) targeting androgen production and androgen receptor (AR) signaling is the primary antihormonal therapy in the treatment of advanced prostate cancer (PCa). However, no clinically established molecular biomarkers have been identified to predict the effectiveness of ADT before starting ADT. The tumor microenvironment of PCa contains fibroblasts that regulate PCa progression by producing multiple soluble factors. We have previously reported that AR-activating factor-secreted fibroblasts increase the responsiveness of androgen-sensitive, AR-dependent PCa cells to ADT. Thus, we hypothesized that fibroblast-derived soluble factors may affect cancer cell differentiation by regulating cancer-related gene expression in PCa cells and that the biochemical characteristics of fibroblasts may be used to predict the effectiveness of ADT. Here, we investigated the effects of normal fibroblasts (PrSC cells) and three PCa patient-derived fibroblast lines (pcPrF-M5, -M28, and -M31 cells) on the expression of cancer-related genes in androgen-sensitive, AR-dependent human PCa cells (LNCaP cells) and three sublines showing different androgen sensitivities and AR dependencies. The mRNA expression of the tumor suppressor gene NKX3-1 in LNCaP cells and E9 cells (which show low androgen sensitivity and AR dependency) was significantly increased by treatment with conditioned media from PrSC and pcPrF-M5 cells but not from pcPrF-M28 and pcPrF-M31 cells. Notably, no upregulation of NKX3-1 was observed in F10 cells (AR-V7-expressing, AR-independent cells with low androgen sensitivity) and AIDL cells (androgen-insensitive, AR-independent cells). Among 81 common fibroblast-derived exosomal microRNAs that showed 0.5-fold lower expression in pcPrF-M28 and pcPrF-M31 cells than in PrSC and pcPrF-M5 cells, miR-449c-3p and miR-3121-3p were found to target NKX3-1. In only LNCaP cells, the NKX3-1 mRNA expression was significantly increased by transfection of an miR-3121-3p mimic but not that of the miR-449c-3p mimic. Thus, fibroblast-derived exosomal miR-3121-3p may be involved in preventing the oncogenic dedifferentiation of PCa cells by targeting NKX3-1 in androgen-sensitive, AR-dependent PCa cells., (© 2023 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.)

Objectives: Preoperative deep venous thrombosis (DVT) can cause potentially life-threatening postoperative venous thromboembolism (VTE). Lower limb venous ultrasound (LLVU) is a modality that can detect DVT. However, the threshold for performing preoperative LLVU in the population undergoing colorectal resection is controversial. In this context, we evaluated whether a preoperative D-dimer value can identify patients who benefit from LLVU from the perspective of preventing postoperative symptomatic VTE., Methods: Patients undergoing colorectal resection in our institute from 2013 to 2020 were retrospectively enrolled (n=2071). We divided the patients into two groups: the clinical indication group (CG: including patients from 2013 to 2016, n=875) and the D-dimer-orientated group (DG: including patients from 2017 to 2020, n=1196). In the CG, LLVU was performed when DVT was clinically suspected; in the DG, preoperative LLVU was performed in patients with a preoperative D-dimer>1.0 μg/ml., Results: In the surveyed period, 277 LLVUs were performed, among which DVT was detected in 34 cases (12.3%). In the CG, DVT was detected in 0.7% of patients, whereas in the DG, it was detected in 2.3% of patients. Postoperative symptomatic VTE was significantly reduced in the DG at both 3 and 6 months after surgery (p=0.041 and 0.020, respectively). Moreover, Multivariate analysis showed that a past medical history of PE and treatment following the CG protocol were independent risk factors for postoperative symptomatic VTE within 6 months of surgery (p<0.0001 and =0.036, respectively)., Conclusions: LLVU in patients with a preoperative D-dimer>1.0 μg/ml is a useful method to prevent postoperative symptomatic VTE., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2023 The Japan Society of Coloproctology.)

Background/aim: High expression of solute carrier family 20 member 1 (SLC20A1) indicates poor clinical outcomes for patients with breast cancer subtypes treated with endocrine therapy and radiotherapy. However, the association between SLC20A1 expression and clinical outcomes in prostate cancer remains to be determined., Materials and Methods: Open-source datasets (The Cancer Genome Atlas prostate, Stand Up to Cancer-Prostate Cancer Foundation Dream Team, and The Cancer Genome Atlas PanCancer Atlas) were downloaded and analyzed. SLC20A1 expression was analyzed in prostate cancer and normal prostate tissue. Survival analysis using Kaplan-Meier curves and Cox regression analysis were performed to examine patient prognosis, as well as the effects of endocrine therapy and radiotherapy on high SLC20A1 expression in patients with prostate cancer., Results: SLC20A1 was higher in prostate cancer than in normal prostate tissues. High SLC20A1 expression predicted poor disease-free and progression-free survival. Following endocrine therapy, no significant difference in prognosis was observed between patients with high SLC20A1 and those with low SLC20A1 expression. However, following radiotherapy, high SLC20A1 expression tended to be associated with a poor clinical outcome., Conclusion: SLC20A1 may serve as a prognostic biomarker for prostate cancer, and the recommended treatment for patients with high SLC20A1 expression is endocrine therapy., Competing Interests: The Authors have no conflicts of interest to declare., (Copyright 2023, International Institute of Anticancer Research.)

Background: Accurate prognostic estimation is crucial; however, the prognostic value of tumor deposits in gastric cancer remains controversial. This study aimed to investigate their prognostic significance., Methods: Clinicopathological and prognostic data of 1012 gastric cancer patients who underwent R0 or R1 surgery from 2010 to 2017 at the Osaka International Cancer Institute were retrospectively reviewed., Results: Overall, 6.3% patients had tumor deposits, which were associated with Borrmann type, surgical procedure, type of gastrectomy, extent of lymphadenectomy, tumor size, histology, pT, pN, pM, pStage, lymphatic invasion, vascular invasion, preoperative chemotherapy, and postoperative chemotherapy. Tumor deposit-positive patients had worse 5-year disease-free survival (32.60% vs. 92.45%) and overall survival (41.22% vs. 89.37%) than tumor deposit-negative patients. Subgroup analysis regarding pStage II-III also showed significant differences between patients with and without tumor deposits for 5-year disease-free survival (34.15% vs. 80.98%) and overall survival (43.17% vs. 75.78%). Multivariable analysis showed that older age, undifferentiated histology, deeper tumor invasion, lymph node metastasis, distant metastasis, and presence of tumor deposits were significantly correlated with early tumor recurrence and shorter survival time; these factors were identified as independent prognostic factors. The 5-year disease-free survival of tumor deposit-positive patients was significantly worse than that of patients in the pStage III group and comparable to that of patients in the pT4, pN3, and pM1 groups. The 5-year overall survival of tumor deposit-positive patients was comparable to that of the pT4, pN3, pM1, and pStage III groups., Conclusions: Tumor deposits are strong and independent predictors of tumor recurrence and poor survival., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Macroglossia is one of the clinical signs that emerges in patients with amyotrophic lateral sclerosis (ALS) who are undergoing invasive ventilation., Objective: We aimed to investigate the relationship between the progression of macroglossia and the clinical characteristics during the advanced stages of ALS., Methods: Forty-one patients with ALS using invasive ventilation with tracheostomy were prospectively followed over a 3-year period. We evaluated the prevalence of macroglossia, motor disabilities including oral function, communication ability (communication stage I to V) as a marker of disease progression, and nutritional factors. We analyzed the potential factors affecting the progression of macroglossia using a multivariate logistic analysis., Results: The number of patients with macroglossia was increased during the follow-up (from 24.4 to 53.7%), while the communication stage progressed from 2.6 in average (SD 1.7) to 3.5 (1.4). During the study, body weight increased, while energy intake decreased, suggesting progressive hypometabolism. Eight patients had newly developed macroglossia during the study and showed greater progression of communication impairment than those without macroglossia. Multivariate logistic regression analysis showed that communication impairment was a factor associated with macroglossia., Conclusion: Macroglossia in advanced ALS with invasive ventilation is associated with disease progression., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: In Japan, there are no substantial reports on robotic-assisted colectomy because few institutions performed the procedure, as it was not covered by national insurance until March 2022., Aim: This study aimed to evaluate the safety and feasibility of robotic-assisted colectomy for patients with curatively resectable colon cancer in Japan., Methods: This multi-institutional, prospective, single-arm, observational study enrolled patients diagnosed with curatively resectable clinical stage I-IIIC colon adenocarcinoma with D2 or D3 lymph node dissection and treated with robotic-assisted colectomy. The primary endpoint was the conversion rate to laparotomy. The non-inferiority of outcomes for robotic-assisted colectomy versus laparoscopic colectomy, which was determined from historical data, was verified., Results: One hundred patients were registered between July 2019 and March 2022 and underwent robotic-assisted colectomy performed by seven expert surgeons at six institutions. Thirteen patients were excluded because their surgeons had insufficient experience performing robotic-assisted colectomy; therefore, 87 patients were eligible for the primary endpoint analysis. There was no conversion in these 87 patients, and robotic-assisted colectomy was non-inferior to laparoscopic colectomy in terms of conversion rate (90% confidence interval 0-3.38, p  = 0.0006). No intraoperative adverse events occurred, and no mortality was observed in a total of 100 patients. The rate of patients with Clavien-Dindo complications grade III or higher was 4%., Conclusion: This study showed the non-inferiority of the conversion rates between robotic-assisted colectomy and laparoscopic colectomy. Favorable perioperative outcomes also suggest the safety and feasibility of robotic-assisted colectomy., Competing Interests: Yusuke Kinugasa received lecture fees from Intuitive Surgical G.K. All other authors have no conflict of interests to declare for this article. Ichiro Takemasa is an editorial member of Annals of Gastroenterological Surgery., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

The anastomotic technique after esophagectomy is of great interest in the prevention of anastomotic complications that adversely affect postoperative recovery. This study aimed to compare the clinical outcomes of modified Collard (MC) and circular stapled (CS) anastomoses after esophagectomy. A total of 504 consecutive patients with thoracic esophageal cancer who underwent esophagectomy and cervical esophagogastric CS or MC anastomosis from January 2013 to December 2019 were enrolled. Out of 504 patients, 134 and 370 underwent CS and MC anastomoses. The frequency of anastomotic leakage and stricture was significantly lesser in the MC group than in the CS group (3.0 vs. 10.5%, P = 0.0014 and 11.1 vs. 34.3%, P < 0.001, respectively). CS anastomosis was an independent risk factor for anastomotic stricture (odds ratio, 4.89; P < 0.001). Oral intake was significantly higher in the group without anastomotic stricture than in the group with anastomotic stricture at 2, 3, and 6 months postoperatively (P < 0.001, P = 0.013, and P < 0.001, respectively). The percentage body weight loss (%BWL) was -12.2% in the group with anastomotic stricture and -7.5% in the group without anastomotic stricture at 3 months postoperatively (P = 0.0012). Anastomotic stricture was an independent factor associated with %BWL (odds ratio, 4.86; P = 0.010). Propensity score-matched analysis, which included 88 pairs of patients, confirmed a significantly lower anastomotic stricture rate in the MC group than in the CS group (10.2 vs. 35.2%, P < 0.001). MC anastomosis is better than CS anastomosis for reducing the frequency of anastomotic stricture, which may be useful for maintaining early postoperative nutritional status., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Surgical site infections are common after pancreaticoduodenectomy. Our institution routinely performs intraoperative bile culture with pancreaticoduodenectomy. Herein we examined whether antibiotic selection based on bile culture analysis reduced the surgical site infection risk after pancreaticoduodenectomy., Methods: A total of 349 patients underwent pancreaticoduodenectomy with intraoperative bile cultures in our institution between 2008 and 2019. Patients were categorized into "group A" (196 patients who underwent pancreaticoduodenectomy between 2008 and 2013) or "group B" (153 patients who underwent pancreaticoduodenectomy between 2018 and 2019). Group A received cefazoline perioperatively and for 2 days postoperatively, whereas group B received piperacillin-tazobactam instead based on the bile culture findings in group A., Results: In group A, 91 (46.4%) intraoperative bile cultures were positive, and surgical site infections occurred in 61 patients (31.1%). A total of 32 patients had both positive bile culture and surgical site infection, of whom 23 (71.9%) exhibited the same microorganisms in the biliary and surgical site infection cultures. Due to the common finding of cefazoline-resistant Enterococcus spp. and Enterobacter spp. in group A, group B received piperacillin-tazobactam. Surgical site infection incidence in group B was 18.3% (n = 28), which was significantly lower than in group A (P = .006). Cefazoline-resistant Enterococcus spp. and Enterobacter spp., respectively, were cultured in 69.8% and 24.3% of patients with preoperative biliary drainage, compared with 32.2% and 9.7% of patients without preoperative biliary drainage., Conclusion: The perioperative selection of antibiotics based on bile culture findings at pancreaticoduodenectomy can reduce the incidence of surgical site infection., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Regorafenib has shown significant survival benefit as a salvage therapy for colorectal cancer; however, its starting dose has been controversial in recent studies. Therefore, we conducted a prospective study on the efficacy and safety of the dose reduction of regorafenib to 120 mg. Patients received 120 mg regorafenib once per day for 3 weeks, followed by a 1-week off-treatment period. The primary endpoint was the investigator-assessed disease control rate (DCR). Sixty patients were registered, and the DCR was 38.3% with a median progression-free survival of 2.5 months (95% confidence interval [CI] 1.9-3.7) and median overall survival of 10.0 months (95% CI 6.9-15.2). Common grade 3-4 adverse events were hand-foot skin reaction and hypertension (20.0% each). The results of administration of 120 mg regorafenib as the starting dose are consistent with reports from prior phase III trials, which used starting doses of 160 mg. This lower initiating dose of regorafenib may be beneficial to certain patient populations. This clinical trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR number UMIN000018968, registration date: 10/09/2015)., (© 2023. The Author(s).)

Purpose: This study aimed to elucidate the effects of neuraxial analgesia on labor in women classified based on the Robson classification system., Methods: We retrospectively reviewed the clinical data of singleton cephalic nulliparous deliveries in labor at term between January 2018 and December 2021 and compared obstetrical outcomes between deliveries with and without neuraxial analgesia in women of Robson group 1 (spontaneous labor) and group 2a (induced labor). Statistical analyses were performed using the Wilcoxon ranked-sum test, Fisher's exact test, and logistic regression model. Statistical significance was set at p < 0.05., Results: We identified 2726 deliveries during the period, of which 387 deliveries (215 with analgesia and 172 without analgesia) were in Robson group 1 and 502 deliveries (258 with analgesia and 244 without analgesia) in Robson 2a. In Robson group 1 pregnancies, the cesarean section (CS) rate was higher in those who received analgesia (15%) than in those who did not (3%) (p = 0.0001). Multivariate analysis revealed that labor with analgesia was a significant risk factor for CS (p < 0.0001). Similarly, in Robson group 2a pregnancies, we observed a higher CS rate in those with analgesia than in those without analgesia (18 vs. 11%, p = 0.042)., Conclusion: A higher CS rate was observed in deliveries with analgesia than in those without analgesia both in the Robson group 1 and group 2a pregnancies., (© 2022. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Background: Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19-9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT)., Methods: This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured., Results: Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03-4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039)., Conclusion: Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis., (© 2023. The Author(s).)

The gastrointestinal stromal tumor(GIST)guidelines state that the use of neoadjuvant chemotherapy(NAC)for curable GIST is not apparent. However, NAC is performed for massive rectal GIST at our hospital to reduce surgical invasion and improve surgical results. The cases were a 39-year-old man, a 48-year-old man, and a 78-year-old man. The site was Rb in all cases, and the maximum diameters at the rectal GIST diagnosis were respectively 70 mm, 75 mm, and 60 mm, which were massive tumors. Imatinib mesylate(imatinib)was started as NAC. The duration of NAC was respectively 6, 11, and 12 months. The maximum tumor diameter on preoperative CT was smaller than before NAC, and the average reduction rate was 23%. Two cases underwent laparoscopic abdominal perineal resection, and 1 underwent laparoscopic ultra-low anterior resection and ileostomy. No perioperative complications of Clavien-Dindo classification Grade Ⅱ or higher were unsettled. All patients were in the high risk group and received imatinib as postoperative adjuvant chemotherapy. Currently, respectively 2 years and 3 months, 1 year and 2 months, and 1 year after surgery, all are alive without recurrence. NAC with imatinib has contributed to minimally invasive and radical surgery for giant rectal GIST.

Purpose: The incidence of adenocarcinoma of the esophagogastric junction (AEG) and proximal gastric cancer (PGC) is rising worldwide. Recently, the use of indocyanine green (ICG) tracer-guided surgery has been reported; however, its efficacy for total/proximal gastrectomy has not been clarified. We evaluated the feasibility and safety of ICG fluorescent marking for tumor localization in AEG/PGC treatment by laparoscopic surgery., Methods: We enrolled patients with AEG/PGC from October 2016 to March 2019 from a prospectively registered database. On the day before surgery, ICG markings were made at four locations just at the edge of the tumor by gastrointestinal fiberscope examination. Surgery was performed while viewing the fluorescence image of ICG, and the proximal portions of the esophagus and the distal portion of the stomach were resected at the edge of the area where ICG had spread., Results: We enrolled 130 patients with AEG/PGC. Overall, 107 patients were eventually included in the study: AEG n = 64 (60%) and PGC n = 43 (40%). ICG markings were detected intraoperatively in all cases, and cancer invasion into the resection lines of the esophagus and stomach, performed based on ICG fluorescence images, was negative in all cases. The median visible range of ICG fluorescence was 22.5 mm. ICG diffusion expanded 20 mm proximal for AEG. There were no adverse events associated with endoscopic ICG injection., Conclusion: ICG fluorescence imaging is feasible and safe and can potentially be used as a tumor-marking agent for determining the surgical resection line for total/proximal gastrectomy in AEG and PGC treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Following injury, skeletal muscle regenerates but fatty tissue accumulation is seen in aged muscle or muscular dystrophies. Fibro/adipogenic progenitors (FAPs) are key players in these events; however, the effect of primary cilia on FAPs remains unclear. Here, it is reported that genetic ablation of trichoplein (TCHP), a ciliary regulator, induces ciliary elongation on FAPs after injury, which promotes muscle regeneration while inhibiting adipogenesis. The defective adipogenic differentiation of FAPs is attributed to dysfunction of cilia-dependent lipid raft dynamics, which is critical for insulin/Akt signaling. It is also found that interleukin (IL) 13 is substantially produced by intramuscular FAPs, which are upregulated by ciliary elongation and contribute to regeneration. Mechanistically, upon injury, long cilia excessively activate the IL33/ST2/JNK axis to enhance IL13 production, facilitating myoblast proliferation and M2 macrophage polarization. The results indicate that FAPs organize the regenerative responses to skeletal muscle injury via cilia-mediated insulin/Akt and ST2/JNK signaling pathways., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Laparoscopic Billroth-I gastroduodenostomy using a delta-shaped anastomosis is safe and feasible. However, it is often difficult to perform in patients who have a short posterior wall of the duodenum. Thus, we have developed a new method named duodenal overlap functional anastomosis with linear stapler (DOLFIN). We hereby report the technical details of the new method and our preliminary experience performing it., Methods: After the completion of lymphadenectomy, the duodenum was transected craniocaudally with an endoscopic linear stapler. The hepatoduodenal mesentery was dissected approximately 4 cm along the duodenal bulb, and the anastomosis between the posterior wall of the stomach and the lesser curvature of the duodenum was created. The common entry hole was then transected using an endoscopic linear stapler, and the anastomosis was finally completed., Results: There were 36 patients with gastric cancer who underwent laparoscopic distal gastrectomy (LDG) or robotic distal gastrectomy (RDG) with B-I reconstruction using DOLFIN. There were no postoperative complications classified as C-D grade 3 or more and complications related to anastomosis, such as anastomotic leak or stenosis., Conclusions: Our DOLFIN gastroduodenostomy can be performed safely. In addition, it results in good postoperative outcomes. A long-term comparative study is required to further evaluate the clinical usefulness of this method., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colorectal cancer (CRC) is a major cause of cancer-related deaths. Metastasis is enhanced through epithelial-mesenchymal transition (EMT), a process primarily induced by the transforming growth factor beta (TGF-β)-mediated canonical Smad pathway. This study focused on plexin D1 (PLXND1), a chemoreceptor for the ligand SEMA3E to mechanosensory, showing that PLXND1 induces EMT via activation of the PI3K/AKT pathway in CRC cells. The findings showed that PLXND1-knockdown decreases cell migration and invasion significantly, and that the binding of p61-SEMA3E to the PLXND1 enhances the invasiveness and migration through EMT. Furin inhibitor suppresses EMT, decreasing cell migration and invasion. Furin cleaves full-length SEMA3E and converts it to p61-SEMA3E, suggesting that furin inhibitors block PLXND1 and p61-SEMA3E binding. Furin is a potential therapeutic target for the purpose of suppressing EMT by inhibiting the binding of p61-SEMA3E to PLXND1. In vivo experiments have shown that PLXND1-knockdown suppresses EMT. Mesenchymal cells labeled with ZEB1 showed heterogeneity depending on PLXND1 expression status. The high-expression group of PLXND1 in 182 CRC samples was significantly associated with poor overall survival compared with the low-expression group (P = 0.0352, median follow-up period of 60.7 months) using quantitative real-time polymerase chain reaction analysis. Further research is needed to determine whether cell fractions with a different expression of PLXND1 have different functions., (© 2022. Society of Surgical Oncology.)

Background: We previously reported the stump closure method for the remnant pancreas in distal pancreatectomy, in which soft coagulation and polyglycolic acid felt attached with fibrin glue were utilized. Transpancreatic mattress suture with polyglactin 910 woven mesh was recently reported as a novel stump closure technique. We developed the modified transpancreatic mattress suture with polyglactin 910 woven mesh method, which combined our polyglycolic acid felt method with the transpancreatic mattress suture with polyglactin 910 woven mesh method., Methods: The polyglycolic acid felt group included patients undergoing distal pancreatectomy in whom the pancreatic stump was closed with the polyglycolic acid felt method from 2017 to 2018 (n = 54); whereas the modified transpancreatic mattress suture with polyglactin 910 woven mesh group included those whose stump was closed with the modified transpancreatic mattress suture with polyglactin 910 woven mesh method from 2019 to 2020 (n = 51). Perioperative parameters, including grade B/C postoperative pancreatic fistula (clinically relevant postoperative pancreatic fistula), were assessed according to the stump closure method., Results: The incidence of clinically relevant postoperative pancreatic fistula was significantly lower in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group than in the polyglycolic acid felt group (7.8% vs 22.2%, P = .036). In multivariate analysis, the use of neoadjuvant chemoradiotherapy and the transpancreatic mattress suture with polyglactin 910 woven mesh method were independent factors for preventing clinically relevant postoperative pancreatic fistula (P = .011 and 0.0038, respectively). Moreover, in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group, the incidence of clinically relevant postoperative pancreatic fistula in patients with a thick pancreas (≥13 mm, 6.7%) was comparably as low as that in patients with a thin pancreas (<13 mm, 9.5%)., Conclusion: The modified transpancreatic mattress suture with polyglactin 910 woven mesh method is an effective stump closure technique to prevent clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Our results warrant further prospective investigation to evaluate the efficacy of the modified transpancreatic mattress suture with polyglactin 910 woven mesh method compared with other standard closure methods (eg, stapler closure or hand-sewn closure)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Laparoscopic total gastrectomy for early proximal gastric cancer is widely performed. Recently, the number of laparoscopic proximal gastrectomies performed, a surgery limited to early proximal gastric cancer, has gradually increased. However, evidence for the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy is insufficient. Therefore, this study aimed to clarify and compare the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy with novel valvuloplastic esophagogastrostomy for treatment of clinical stage I proximal gastric cancer., Methods: This study included 111 patients who underwent laparoscopic total gastrectomy or laparoscopic proximal gastrectomy for the treatment of upper third clinical stage I gastric cancer between April 2004 and December 2017. After adjusting for propensity score matching analysis, we compared the postoperative complications, nutritional status, and long-term outcomes between the two groups., Results: After matching the inclusion criteria, 56 patients (28 in each group) were enrolled. No significant differences were noted in the postoperative complications between the two groups. While laparoscopic proximal gastrectomy was associated with lower albumin levels, lower body weight loss was seen by 1 year after surgery and higher hemoglobin levels by 1, 2, and 3 years after surgery. No significant differences were observed in the 3-year overall survival and 3-year recurrence-free survival between the laparoscopic total gastrectomy and laparoscopic proximal gastrectomy groups (P = 0.74 and 0.72, respectively)., Conclusion: Laparoscopic proximal gastrectomy and laparoscopic total gastrectomy for patients with upper third clinical stage I gastric cancer are feasible as regards its safety and outcomes., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background/aim: Previous studies have shown that postoperative adjuvant chemotherapy improves overall survival in patients with stage III colorectal cancer (CRC). However, adjuvant chemotherapy may not be necessary for some patients. This study aimed to develop a new nutritional-inflammation score, which would be useful in identifying a favorable prognosis group among stage III CRC patients., Patients and Methods: This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and a new prognostic model was developed., Results: Multivariate analyses in TS revealed that lymph node metastasis (N2) (p=0.002), low albumin (p=0.017), high monocyte counts (p=0.008), and low platelet counts (p=0.018) were independent risk factors for disease free survival (DFS). The Kansai prognostic score (KPS) was assessed by 1 point each for <3.5 g/dl albumin level, >450 monocyte counts, and <1.65×10 5 platelet counts. Using KPS, DFS and overall survival (OS) were validated in VS. The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS., Conclusion: KPS serves as a new model for the prognosis of patients with stage III CRC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The benefits of robotic gastrectomy (RG) over laparoscopic gastrectomy (LG) remain controversial. This single-center, propensity score-matched study aimed to compare the outcomes of RG with those of LG for treating gastric cancer., Methods: We searched the prospective gastric cancer database of our institute for patients with gastric cancer who underwent RG or LG between January 2014 and December 2019, excluding patients with remnant stomach cancer and those who underwent concurrent surgery for comorbid malignancies. One-to-one propensity score matching was performed to reduce bias from confounding patient-related variables, and short- and long-term outcomes were compared between the groups., Results: We identified 1189 patients who underwent LG (n = 979) or RG (n = 210). After propensity score matching, we selected 210 pairs of patients who underwent LG (distal gastrectomy, 138; total or proximal gastrectomy, 72) or RG (distal gastrectomy, 143; total or proximal gastrectomy, 67). RG was associated with a significantly shorter operative time (RG = 201 min vs. LG = 231 min, p = 0.0051), less blood loss (RG = 13 mL vs. LG = 42 mL, p < 0.0001), lower postoperative morbidity (RG = 1.0% vs. LG = 4.8%, p = 0.0066), and a shorter postoperative hospital stay (p = 0.0002) than LG. Drain amylase levels on postoperative Days 1 and 3 in the RG group were significantly lower than those in the LG group (p < 0.0001)., Conclusions: RG is a safe and feasible treatment for gastric cancer, with a shorter operative time, less blood loss, and lower postoperative morbidity than LG. The application of robotics in minimally invasive gastric cancer surgery may offer an alternative to conventional surgery. Multicenter, prospective, randomized controlled trials comparing RG with conventional LG are needed to establish the feasibility and efficacy of minimally invasive gastric cancer surgery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Addition of perioperative multi-agent chemotherapy to the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. We conducted a phase II study to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as triplet neoadjuvant chemotherapy in patients with LARC., Methods: Patients received neoadjuvant irinotecan and oxaliplatin and capecitabine and then underwent total mesorectal excision. The primary study endpoint was the pathological complete response (pCR) rate., Results: Between June 2013 and December 2016, 55 patients were enrolled in the study. Forty-two (77.8%) of 54 completed the study protocol. The pCR rate was 7.7% (95% CI 3.0% to 18.2%). The 3-year local recurrence rate was 3.9%, the 3-year disease-free survival (DFS) rate was 77.3, and the 3-year overall survival rate was 96.0%., Conclusion: XELOXIRI neoadjuvant chemotherapy appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate, the local recurrence rate, 3-year DFS, and measures of safety met current standards., Competing Interests: I.T., T.M., and Y.D. are Editorial Board Members of AGS., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

Background/aim: p62 (also known as sequestosome 1) is involved in cancer progression, and high expression of p62 indicates poor clinical outcome in several cancer types. However, the association between p62 gene expression and cancer stem cells (CSCs) in breast cancer subtypes remains unclear., Materials and Methods: In the present study, genomic datasets of primary breast cancer (The Cancer Genome Atlas, n=593; and Molecular Taxonomy of Breast Cancer International Consortium, n=2,509) were downloaded. p62 Expression was then examined in normal and breast cancer tissues derived from the same patients. Kaplan-Meier and multivariate Cox regression analyses were employed to evaluate disease-specific survival. Next, the effect on cell viability and in vitro tumor-sphere formation of p62 knockdown using targeted small interfering RNA was assessed by using cells with high activity of aldehyde dehydrogenase 1 (ALDH1 high )., Results: Patients with normal-like, luminal A or luminal B breast cancer with p62 high had poor prognosis. Furthermore, patients with p62 high ALDH1A3 high luminal B type also exhibited poor prognoses. Knockdown of p62 suppressed viability and tumor-sphere formation by ALDH1 high cells of the luminal B-type cell lines BT-474 and MDA-MB-361. These results suggest that p62 is essential for cancerous progression of ALDH1-positive luminal B breast CSCs, and contributes to poor prognosis of luminal B breast cancer., Conclusion: p62 is potentially a prognostic marker and therapeutic target for ALDH1-positive luminal B breast CSCs., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The intestinal environment plays important roles in mucosal barrier homeostasis and intestinal inflammation, as clarified in studies using experimental animals but not in humans., Aims: We investigated whether environmental changes in the fecal stream cause phenotypic changes in the human mucosal barrier., Methods: We obtained human ileal samples after fecal stream diversions in patients with rectal cancer or Crohn's disease. We investigated the bacterial load and diversity in the human defunctioned ileum, defined as the anal side of the ileum relative to the ileostomy. We also examined the epithelium and lamina propria cell phenotypes in the defunctioned ileum., Results: After fecal stream diversion, bacterial loads decreased significantly in the defunctioned ileum. Based on the Chao1, Shannon, and observed species indices, the diversity of mucosa-associated microbiota was lower in the defunctioned ileum than in the functional ileum. Moreover, the healthy defunctioned ileum showed reductions in villous height, goblet cell numbers, and Ki-67 + cell numbers. Additionally, interferon-γ + , interleukin-17 + , and immunoglobulin A + cell abundance in the lamina propria decreased. After the intestinal environment was restored with an ileostomy closure, the impaired ileal homeostasis recovered. The defunctioned ileum samples from patients with Crohn's disease also showed reductions in interferon-γ + and interleukin-17 + cell numbers., Conclusions: Fecal stream diversion reduced the abundance and diversity of intestinal bacteria. It also altered the intestinal mucosal barrier, similar to the alterations observed in germ-free animals. In patients with Crohn's disease, Th1 and Th17 cell numbers were attenuated, which suggests that the host-microbiome interaction is important in disease pathogenesis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Body composition changes during neoadjuvant therapy and their clinical significance have not been clarified. The present study aimed to investigate body composition changes during neoadjuvant chemoradiation therapy (NACRT) in patients with distal bile duct cancer and the clinical impact on postoperative complications and the prognosis. A total of 16 patients with distal bile duct cancer who underwent curative resection after NACRT were retrospectively evaluated. The area of skeletal muscle, visceral fat and subcutaneous fat on computed tomography and immunological and nutritional indices were assessed before and after NACRT. All 16 patients completed NACRT followed by pancreaticoduodenectomy without mortality. There was no significant change in the skeletal muscle mass index (SMI) during NACRT. Of the 16 patients, nine (56%) were defined as sarcopenic before NACRT, and eight (50%) met the criteria for sarcopenic after NACRT. The SMI and total fat area were significantly associated with postoperative pancreatic fistula (POPF) (P=0.019 and P=0.007, respectively). The patients with sarcopenia had a shorter disease-free survival time and overall survival time in comparison to patients without sarcopenia (P=0.025 and P=0.115, respectively). In conclusion, NACRT for distal bile duct cancer did not significantly affect the body composition, or the immunological or nutritional indices. Sarcopenia after NACRT was significantly associated with early recurrence in patients with distal bile duct cancer who received NACRT., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. The accuracy of a PDAC diagnosis based on endoscopic ultrasonography-guided fine-needle aspiration cytology can be strengthened by performing a rapid on-site evaluation (ROSE). However, ROSE can only be performed in a limited number of facilities, due to a relative lack of available resources or cytologists with sufficient training. Therefore, we developed the Mathematical Technology for Cytopathology (MTC) algorithm, which does not require teaching data or large-scale computing. We applied the MTC algorithm to support the cytological diagnosis of pancreatic cancer tissues, by converting medical images into structured data, which rendered them suitable for artificial intelligence (AI) analysis. Using this approach, we successfully clarified ambiguous cell boundaries by solving a reaction-diffusion system and quantitating the cell nucleus status. A diffusion coefficient ( D ) of 150 showed the highest accuracy (i.e., 74%), based on a univariate analysis. A multivariate analysis was performed using 120 combinations of evaluation indices, and the highest accuracies for each D value studied (50, 100, and 150) were all ≥70%. Thus, our findings indicate that MTC can help distinguish between adenocarcinoma and benign pancreatic tissues, and imply its potential for facilitating rapid progress in clinical diagnostic applications.

Background: To evaluate the possible clinical use of the compressed sensing-volumetric-interpolated breath-hold examination (CS-VIBE) in patients with liver tumors by evaluating tumor contrast enhancement effect by radiologists., Methods: We examined 22 patients with pathologically confirmed neoplastic lesions in the liver and 62 patients with lesions confirmed by imaging and clinical observation. To evaluate image quality, dynamic contrast-enhanced multiphase breath-hold magnetic resonance imaging was performed. The contrast agent used in this study was gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid. Image quality was assessed by three radiologists experienced in this field. Using a four-point scale, we evaluated the gradual contrast enhancement effect of the portal vein to determine whether a decent arterial phase could be obtained. We assessed interobserver agreement using the Fleiss kappa to evaluate image quality between readers. The detection and evaluation of the tumor itself by its enhancement effects are very important in contrast studies. Thus, we evaluated the contrast enhancement effect of the tumors on a three-point scale in 26 patients already known to have hypervascularized tumors using ultrasound or computed tomography as assessed by experienced radiologists., Results: In terms of contrast enhancement effects of the portal vein, the mean value of the readers was 1.85 in the first phase, 2.07 in the second phase, 2.66 in the third phase, 3.05 in the fourth phase, and 3.24 in the fifth phase. Moreover, the interreader agreement was moderate (kappa 0.400-0.502) for all evaluated scores. In the signal of the portal vein, the score of the second arterial phase increased gradually, and in the third arterial phase, the mean score varied from 2 to 3. Compared with ultrasound or computed tomography, CS-VIBE identified 92.3% tumors with hypervascularized tumors (24 of 26 patients with findings hypervascularized tumors). In the results, the interreader agreement was fair to moderate (kappa 0.414-0.521)., Conclusions: We obtained multiphase images, including at least one phase, which are useful for the evaluation of liver tumors. Furthermore, the radiologist was able to detect the tumor as before. Therefore, compressed sensing-volumetric-interpolated breath-hold examination is clinically useful in Ethoxybenzyl liver studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-850/coif). DY, YA, CM, NS, YT, SS and KS report that they were provided work in progress sequence from Siemens. KS reports grants were provided by Eisai, Bayer, GE pharmaceutical, Gerbet, FUJIFILM Toyama Chemical, Nihon Medi-physics and Daiichi-Sankyo, and personal fees were provided by Eisai, Bayer, GE pharmaceutical, Gerbet, FUJIFILM Toyama Chemical and Nihon Medi-physics. KM and DN are current employees of Siemens Healthcare. The authors have no other conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Postoperative carcinoembryonic antigen (post-CEA) has recently been reported to be a reliable prognostic factor for colon cancer. However, most clinicians decide whether or not to conduct adjuvant chemotherapy (AC) for stage II colon cancer according to major guidelines, which do not include post-CEA in their high-risk criteria. The present study aimed to assess post-CEA in stage II colon cancer for which the significance of AC is unknown. The present study analyzed 199 consecutive patients with stage II colon cancer who underwent curative surgery between January 2007 and December 2016. The CEA value was considered high when it was ≥5.0 ng/ml. The prognostic value of high post-CEA values was assessed. Overall, 19 patients exhibited high post-CEA levels. Kaplan-Meier survival curve analysis demonstrated that patients with high post-CEA levels had significantly worse relapse-free survival (RFS) and overall survival (OS) than those with normal post-CEA [RFS, 63.5 (high post-CEA) vs. 88.0% (normal post-CEA), P=0.003; OS, 76.5 (high post-CEA) vs. 96.8% (normal post-CEA), P<0.001]. Multivariate analysis demonstrated that high post-CEA remained a significant independent risk factor for worse RFS [hazard ratio (HR), 3.98; P=0.006]. The same was also demonstrated for patients without AC (HR, 5.43; P=0.008). To the best of our knowledge, the present study was the first to demonstrate that high post-CEA levels may be an indicator of high-risk stage II colon cancer, even for patients without AC. These results highlight the need for a multicenter prospective study., Competing Interests: TM was supported by donations from Kinshukai Medical Corporation. The other authors declare that they have no competing interests., (Copyright: © Morimoto et al.)

Tri- and tetra-fluorinated [7]helicenes are photolabile and undergo a double fluorine atom transfer. Herein, we show that the transferred product further undergoes a skeletal transformation on silica gel. The transformation begins with activation of the allylic C-F bond on the silanol surface. Then, the resulting carbocation readily undergoes a regioselective nucleophilic aromatic substitution with water, depending on the position of the fluorine substituents. Hexafluoro-2-propanol also activated the allylic C-F bond and acted as a nucleophile. These findings support the generation of a highly reactive cationic electrophilic intermediate in the successive transformations involving fluorine atoms., (© 2022 Wiley-VCH GmbH.)

Background: Transcription-reverse transcription concerted reaction (TRC) is recognized as a useful method for detecting free cancer cells in the peritoneal cavity and predicting peritoneal recurrence in patients with gastric cancer. Nonetheless, the clinical significance of TRC in laparoscopic surgery remains unclear. This study aimed to evaluate the clinical importance of carcinoembryonic antigen (CEA) messenger RNA (mRNA) level in peritoneal lavage fluids measured by TRC in laparoscopic surgery for locally advanced gastric cancer., Methods: We enrolled patients with locally advanced gastric cancer who underwent laparoscopic gastrectomy. Peritoneal lavage fluids were collected prior to gastrectomy, and the TRC method was employed to quantify CEA mRNA in peritoneal washes. Overall survival (OS), recurrence-free survival (RFS), and peritoneal recurrence-free survival (PRFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) for CEA mRNA positivity., Results: A total of 100 patients were analyzed in this study. Overall, 22 patients (22%) exhibited CEA mRNA positivity in peritoneal lavage fluids, as measured by TRC. No significant association between CEA mRNA levels and clinicopathological characteristics was observed. Patients who were CEA mRNA-positive in peritoneal lavage fluids had significantly worse OS, RFS, and PRFS than those who were CEA mRNA-negative (p = 0.0059, p < 0.0001, and p = 0.0022, respectively). In the univariate Cox model, the HR for all-cause mortality in CEA mRNA-positive versus CEA mRNA-negative patients was 3.60 (95% CI, 1.33-9.55; p = 0.0129). Multivariate analysis revealed that CEA mRNA positivity was a significant independent factor for recurrence., Conclusions: TRC enables the detection of free cancer cells in the peritoneal cavity and CEA mRNA levels can help predict the prognosis, even in laparoscopic gastrectomy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Intraoperative fluid restriction is reported to be associated with reduced postoperative tissue edema and decreased incidence of postoperative pancreatic fistula (POPF) in pancreatic surgery. However, there is limited information regarding the postoperative approach to prevent postoperative tissue edema and reduce POPF., Methods: Patients undergoing distal pancreatectomy from 2013 to 2018 in our institute were retrospectively enrolled (n = 128). The patients were classified into the two groups: an early diuresis group (ED group: patients administered diuretic agents on postoperative day 2 or earlier between 2016 and 2018, n = 69) and a conventional diuresis group (CD group: patients administered diuretic agents on postoperative day 3 or later between 2013 and 2015, n = 59). Postoperative tissue edema assessed by CT imaging and the incidence of clinically relevant POPF (CR-PF; grade B or C) were compared., Results: Postoperative tissue edema was significantly reduced in the ED group (p < 0.0001). The incidence of CR-PF was lower in the ED group (19% vs. 32%, p = 0.082), especially in patients with postoperative diuresis on POD 1 (12%, p = 0.044)., Conclusion: Early and aggressive postoperative diuresis potentially reduced postoperative visceral tissue edema. This postoperative approach to prevent tissue edema may reduce the incidence of CR-PF in pancreatic surgery., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We investigated the incidence of weight gain and its related factors in patients with amyotrophic lateral sclerosis (ALS) who underwent tracheostomy and invasive ventilation (TIV). Seventy-eight patients with ALS and TIV were enrolled and followed up prospectively. We clarified the clinical profiles of patients with increased weight following TIV and examined chronological variations in their body mass index (BMI), energy intake, and serum albumin levels. Post follow-up, we determined their disease stage according to their communication impairment (stage I to V) and investigated factors associated with BMI increase following TIV. Patients with a post-TIV BMI increase ≥1.86 kg/m 2 demonstrated a higher incidence of ophthalmoplegia (76.2%), total quadriplegia (61.9%), severe communication impairment (stage V; 33.3%), and hypoalbuminemia than those with a BMI increase <1.86 kg/m 2 . Patients with stage V communication impairment exhibited a larger and faster BMI decrease before TIV (mean -4.2 kg/m 2 and -2.5 kg/m 2 /year, respectively); a larger BMI increase (mean +4.6 kg/m 2 ) following TIV, despite lower energy intake; and lower albumin levels post follow-up than those with lower-stage communication impairment. Multilevel linear regression analysis demonstrated an independent association between communication impairment stages (stage V) and a post-TIV BMI increase ( p = 0.030). Weight gain and hypoalbuminemia during TIV in patients with ALS were associated with the disease stage and may be attributable to the neurodegenerative processes that are peculiar to ALS.

Background: Gastric cancer with portal vein tumor thrombus (PVTT) is poor prognosis, and the treatment remains challenging. Regarding surgery, there are only reports of highly invasive laparotomy. We report some techniques of the completely robotic total gastrectomy with thrombectomy and portal vein reconstruction for the patient with gastric cancer and PVTT for the first time., Case Presentation: A 79-year-old man was diagnosed with a 5-cm gastric cancer on the side of the lesser curvature from the middle of the gastric body to the cardia. Computed tomography revealed a massive PVTT extending from the left gastric vein to the portal trunk (28 x 16 mm). There were no other distant metastases. After 3 cycles of the chemotherapy, the PVTT shrank to 19 x 12 mm. After obtaining informed consent from the patient, robotic total gastrectomy with regional lymphadenectomy and thrombectomy were performed. We used the da Vinci Xi Surgical System. A 3-cm incision was made at the umbilicus, and a wound retractor was placed. Five additional ports were placed. The right side suprapancreatic lymph nodes were performed at the time of the thrombectomy. It was important to identify the precise extent of the PVTT with intraoperative ultrasonography before the thrombectomy. After PVTT identification, the portal trunk was clamped above and below the tumor thrombus with vascular clips. The membrane on the anterior wall of the portal trunk around the PVTT was carefully incised with da Vinci Scissors. The tumor thrombus was completely enucleated without separation. The incised part of the portal trunk was reconstructed with continuous 5-0 synthetic monofilament nonabsorbable polypropylene sutures. After removing the vascular clamps, we made sure there was no leakage from the portal vein and no tumor thrombus remnants with intraoperative ultrasonography. Robotic total gastrectomy with lymphadenectomy and Roux-en-Y reconstruction were performed. The patient was discharged without complications. The patient has remained alive for 30 months after surgery., Conclusions: Robotic total gastrectomy with thrombectomy and portal vein reconstruction is a safe, minimally invasive, and precise surgery. It may contribute to improved prognosis of gastric cancer with PVTT when combined with chemotherapy., (© 2022. The Author(s).)

Purpose: Pathological extramural venous invasion (EMVI) is defined as the active invasion of malignant cells into veins beyond the muscularis propria in colorectal cancer. It is associated with poor prognosis and increases the risk of disease recurrence. Specific findings on MRI (termed MRI-EMVI) are reportedly associated with pathological EMVI. In this study, we aimed to identify risk factors for lateral lymph node (LLN) metastasis related to rectal cancer and to evaluate whether MRI-EMVI could be a new and useful imaging biomarker to help LLN metastasis diagnosis besides LLN size., Methods: We investigated 67 patients who underwent rectal resection and LLN dissection for rectal cancer. We evaluated MRI-EMVI grading score and examined the relationship between MRI-EMVI and LLN metastasis., Results: Pathological LLN metastasis was detected in 18 cases (26.9%), and MRI-EMVI was observed in 32 cases (47.8%). Patients were divided into two cohorts, according to LLN metastasis. Multivariate analyses demonstrated that higher risk of LLN metastasis was significantly associated with MRI-EMVI (P = 0.0112) and a short lateral lymph node axis (≥ 5 mm) (P = 0.0002). The positive likelihood ratios of MRI-EMVI alone, LLN size alone, and the combination of both factors were 2.12, 4.84, and 16.33, respectively. Patients negative for both showed better 2-year relapse-free survival compared to other patients (84.4% vs. 62.1%, P = 0.0374)., Conclusions: MRI-EMVI was a useful imaging biomarker for identifying LLN metastasis in patients with rectal cancer. The combination of MRI-EMVI and LLN size can improve diagnostic accuracy., (© 2022. The Author(s).)

Background: Preoperative chemoradiation therapy (CRT) or chemotherapy (CT) followed by surgery is currently being administered for advanced esophageal cancer. However, few studies have directly compared CRT and CT for treating locally advanced esophageal carcinoma. This study aimed to assess postoperative recurrence patterns and post-recurrence outcomes in patients with radical esophagectomy after CRT or triplet CT regimen with docetaxel, cisplatin, and 5-fluorouracil (DCF)., Methods: This study included 325 consecutive patients with thoracic esophageal cancer who received preoperative CRT or DCF followed by curative esophagectomy between January 2010 and December 2019. We compared recurrence patterns after surgery and post-recurrence treatments between CRT and DCF. Locoregional recurrence was defined as recurrences at the primary tumor site or regional lymph nodes. Distant recurrence was defined as non-regional lymph node recurrences, systemic metastases, malignant pleural effusions, or peritoneal metastases., Results: Among 325 patients, 74 received preoperative CF + RT and 251 received preoperative DCF. A propensity score-matched cohort of 53 with CRT and 53 with DCF was included. CRT patients had tumors located in the upper esophagus and had more advanced cancer than DCF patients; however, no differences in patient characteristics were observed in the matched cohort. CRT patients had better histopathological responses and control of locoregional recurrence than DCF patients. On the other hand, distant recurrence, especially in the non-regional lymph node, lung, and pleural dissemination, significantly developed more frequently in CRT patients. Furthermore, CRT patients may have received insufficient post-recurrence treatment, owing to fewer treatment options. Therefore, although there was no difference in recurrence rate in the two groups, CRT patients had significantly poorer post-recurrence survival than DCF patients., Conclusions: Preoperative DCF could reduce distant recurrence after surgery compared to preoperative CRT. The differences in recurrence patterns can be related to the selection of post-recurrence treatment and their prognosis after recurrence., (© 2022 S. Karger AG, Basel.)