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While prostaglandin E 2 (PGE 2 ) is produced in human tumor microenvironment (TME), its role therein remains poorly understood. Here, we examine this issue by comparative single-cell RNA sequencing of immune cells infiltrating human cancers and syngeneic tumors in female mice. PGE receptors EP4 and EP2 are expressed in lymphocytes and myeloid cells, and their expression is associated with the downregulation of oxidative phosphorylation (OXPHOS) and MYC targets, glycolysis and ribosomal proteins (RPs). Mechanistically, CD8 + T cells express EP4 and EP2 upon TCR activation, and PGE 2 blocks IL-2-STAT5 signaling by downregulating Il2ra, which downregulates c-Myc and PGC-1 to decrease OXPHOS, glycolysis, and RPs, impairing migration, expansion, survival, and antitumor activity. Similarly, EP4 and EP2 are induced upon macrophage activation, and PGE 2 downregulates c-Myc and OXPHOS in M1-like macrophages. These results suggest that PGE 2 -EP4/EP2 signaling impairs both adaptive and innate immunity in TME by hampering bioenergetics and ribosome biogenesis of tumor-infiltrating immune cells., (© 2024. The Author(s).)

Cancer cell clusters have a higher capacity for metastasis than single cells, suggesting cancer cell clusters have biological properties different from those of single cells. The nature of de novo cancer cell clusters that are newly formed from tumor masses is largely unknown. Herein, we generated small cell clusters from colorectal cancer organoids and tracked the growth patterns of the clusters up to four cells. Growth patterns were classified into actively growing and poorly growing spheroids (PG). Notch signaling was robustly activated in small clusters immediately after dissociation, and Notch signaling inhibition markedly increased the proportion of PG spheroids. Only a limited number of PG spheroids grew under growth-permissive conditions in vitro, but xenograft tumors derived from Notch inhibited clusters showed growth rates comparable to those of untreated spheroids. Thus, de novo clusters are composed of cells with interchangeable growth fates, which are regulated in a context-dependent manner by Notch signaling., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Introduction: Although abdominoperineal resection (APR) is required for rectal cancer invading the levator ani muscle, its curative outcomes remain poorer than those of other rectal surgeries. 1-3 In particular, the anatomic complexity around the anterior wall of the rectum increases the technical difficulty during APR, resulting in a high frequency of margin involvement that causes local recurrence. In this video, we present the technical details of a robotic perineal-first APR approach., Methods: For a 46 year-old man, locally advanced rectal cancer invading the levator ani muscles was diagnosed. Although total neoadjuvant therapy (8 cycles of induction FOLFOXIRI followed by chemoradiotherapy 50.4 Gy) decreased the tumor size, invasion was suspected still to remain. Therefore, robotic APR was performed. Written informed consent was obtained from the patient. For the perineal-first approach, we created a circular incision around the anus, then divided the fat tissues of the ischiorectal fossa until the levator ani muscle was exposed on both sides. Posterior and anterior dissections were performed along the coccyx and external anal sphincter, respectively. After placement of a lap protector to maintain air-tightness, the robotic approach was initiated. Posterior dissection was performed along the coccyx, then was connected to the already-dissected space created earlier by the perineal approach. Next, the levator ani muscle was divided from the dorsal to the lateral side. Finally, anterior dissection was performed along the prostate, followed by division of the rectourethral muscle, the smooth muscle fibers running vertically. The creation of the already-dissected space on the perineal side offers advantages of robotic manipulation from the abdominal side, especially anterior dissection., Results: We performed robotic APR using the perineal-first approach for 17 consecutive patients (12 men and 5 women) between 2019 and 2023. All 17 patients achieved complete total mesorectal excision with negative margins. The mean time required for the perineal approach was about 25 min. In anterior dissection using the robotic approach, division of the smooth muscle fibers at the perineal body (i.e., rectourethral muscle in males 4 or muscular intermingling in females 5 ) was reproducibly performed in both males and females., Conclusion: Robotic APR with a perineal-first approach can be advantageous in ensuring surgical margin safety (especially for the anterior aspect of the rectum)., (© 2024. Society of Surgical Oncology.)

Background: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges., Methods: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS)., Results: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76)., Conclusions: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers., Methods: Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts., Results: There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes., Conclusions: We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Older patients with cancer already represent the largest proportion of cancer survivors which will further increase in the upcoming years. However, older patients are highly underrepresented in clinical research, leading to a detrimental knowledge gap. Research on important aspects of quality of life (QoL) and associated factors for older patients with cancer is insufficient to date., Aim: The objective of this scoping review therefore is to investigate the dimensions of QoL including functional health, life-relevant values and preferences in older adults with cancer across all tumor entities and health care settings. It will further identify medical, sociodemographic, psychosocial and geriatric aspects associated with QoL in the elderly and compare these with younger cancer patients and older non-cancer cases., Methods: Published articles investigating QoL dimensions and associated factors in older patients with cancer, i.e., exclusively patients ≥65 years or mean/median age ≥ 70 years for age-mixed samples, or that compare results of older with younger cancer patients or with older non-cancer cases will be considered for this scoping review. Older patients with cancer across all tumor entities, disease stages and health care setting will be included. PubMed and PsychINFO databases will be searched for relevant articles. Abstracts and titles will be screened for basic inclusion, and two independent reviewers will conduct a full text screening to evaluate the age criteria and decide on the final inclusion of the study. Data on study and participant characteristics, QoL dimensions and geriatric factors will be extracted using a data extraction sheet. Results will be summarized descriptively to address the objectives of this review., Discussion: The findings of this scoping review will provide valuable insights into central dimensions of QoL, including values, preferences and functional health in older adults with cancer, and help to improve targeted interventions and healthcare planning., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Springer, Matsuoka, Obama, Mehnert-Theuerkauf, Uchitomi and Fujimori.)

There are only a few effective molecular targeted agents for advanced unresectable or recurrent advanced gastric cancer (AGC), which has a poor prognosis with a median survival time of less than 14 months. Focusing on phosphorylation signaling in cancer cells, we have been developing deep phosphoproteome analysis from minute endoscopic biopsy specimens frozen within 20 s of collection. Phosphoproteomic analysis of 127 fresh-frozen endoscopic biopsy samples from untreated patients with AGC revealed three subtypes reflecting different cellular signaling statuses. Subsequent serial biopsy analysis has revealed the dynamic mesenchymal transitions within cancer cells, along with the concomitant rewiring of the kinome network, ultimately resulting in the conversion to the epithelial-mesenchymal transition (EMT) subtype throughout treatment. We present our investigation of intracellular signaling related to the EMT in gastric cancer and propose therapeutic approaches targeting AXL. This study also provides a wealth of resources for the future development of treatments and biomarkers for AGC., Competing Interests: Declaration of interests T.T. and J.A. are co-founders of Proteobiologics Co., Ltd., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Neoadjuvant chemoradiotherapy (nCRT) is employed for the local control of locally advanced rectal cancer; however, its prognostic impact is limited and often impairs pelvic organ function. Therefore, careful patient selection is essential. This study aimed to investigate the impact of nCRT on relapse-free survival (RFS) by stratifying patients according to MRI detected circumferential resection margin (mrCRM) or extramural vascular invasion (mrEMVI), as the ability of MRI findings to identify patients who will have beneficial outcomes from nCRT is uncertain., Methods: We retrospectively analyzed patients with clinical stage II-III lower rectal cancer who underwent surgical resection with or without nCRT between 2010 and 2011 at 69 hospitals in Japan. The impact of nCRT on RFS was evaluated using multivariable Cox regression models in the entire cohort and in subgroups stratified by mrCRM or mrEMVI status., Results: In the entire cohort (nCRT, n = 172; surgery alone, n = 503), nCRT showed a trend toward improved RFS, although the difference was not statistically significant (HR, 0.74; 95 % CI, 0.54-1.03; P = 0.074). Among mrCRM-negative and mrEMVI-negative patients, there were no significant differences in RFS between the nCRT and surgery-alone groups. Among mrCRM-positive patients, nCRT tended to improve the RFS (HR, 0.70; 95 % CI, 0.46-1.06; P = 0.089). Among mrEMVI-positive patients, nCRT significantly prolonged the RFS (HR, 0.62; 95 % CI, 0.38-1.00; P = 0.048)., Conclusions: Compared to surgery alone, nCRT did not significantly improve RFS in the overall population but significantly improved RFS in mrEMVI-positive patients., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Low-grade appendiceal mucinous neoplasm (LAMN) is principally characterized by low-grade cytology without evidence of invasion to other organs. We report a LAMN surgical case whose appendiceal tumor penetrated the sigmoid colon wall. An 87-year-old man was referred for endoscopic resection (ER) of a colon polyp. Despite four ERs over 5 years, the polyp recurred at the same site. Laparoscopic surgery revealed a dilated appendix firmly attached to the sigmoid colon. We performed en bloc resection of both the sigmoid colon and appendix without tumor exposure. The histopathological evaluation showed that the LAMN had penetrated the sigmoid colon wall, forming two polyps on the colonic mucosa. In cases where the appendiceal-colonic fistula is suspected, en bloc resection of the appendix and colon wall should be considered., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

The purpose of our narrative review is to summarize the utilization of social media (SoMe) platforms for research communication within the field of surgery. We searched the PubMed database for articles in the last decade that discuss the utilization of SoMe in surgery and then categorized the diverse purposes of SoMe. SoMe proved to be a powerful tool for disseminating articles. Employing strategic methods like visual abstracts enhances article citation rates, the impact factor, h-index, and Altmetric score (an emerging alternative metric that comprehensively and instantly quantifies the social impact of scientific papers). SoMe also proved valuable for surgical education, with online videos shared widely for surgical training. However, it is essential to acknowledge the associated risk of inconsistency in quality. Moreover, SoMe facilitates discussion on specific topics through hashtags or closed groups and is instrumental in recruiting surgeons, with over half of general surgery residency programs in the US efficiently leveraging these platforms to attract the attention of potential candidates. Thus, there is a wealth of evidence supporting the effective use of SoMe for surgeons. In the contemporary era where SoMe is widely utilized, surgeons should be well-versed in this evidence., (© 2024. The Author(s).)

Background: Numerous studies have described positive relationships between hospital volume (HV) and clinical outcomes in highly complex procedures, including esophagectomies. Although the centralization of surgery has been considered a possible solution for improving clinical outcomes, the HV impact on perioperative healthcare costs is unknown. This study aimed to determine the relationship between HV and perioperative healthcare costs for patients undergoing esophagectomy for esophageal cancer., Methods: This retrospective, nationwide cohort study used Japanese Administrative Claims Database data. Data on esophagectomies performed nationwide in 2015 were extracted. The outcome measure was perioperative healthcare costs per person from the perspective of the insurer. The healthcare costs in outpatient or inpatient settings of any hospital and clinic where patients received treatment were summed up from the month the surgery was performed to 3 months after. Linear regression analyses were conducted to assess the risk-adjusted effects of the HV category (1-4/5-9/10-14/15-) on perioperative costs., Results: A total of 5232 patients underwent an esophagectomy at 584 hospitals. The overall perioperative cost was 20.834 billion Japanese yen (JPY). The median perioperative costs per person for each HV category (1-4/5-9/10-14/15-) were 3.728 (709 patients), 3.740 (658 patients), 3.760 (512 patients), and 3.760 (3253 patients) million JPY, respectively (P = 0.676). Multivariate analyses revealed that each HV category had no significant impact on perioperative costs., Conclusions: There were no significant differences in the perioperative costs between high- and low-volume centers. Esophageal cancer surgery centralization may be achievable without increasing healthcare costs., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Introduction: Recently, antimicrobial resistance has received considerable attention. Broad-spectrum antimicrobial agents are recommended as the initial therapy for post-operative intra-abdominal infections. However, at our institution, we have adopted a tactic of initially treating post-operative intra-abdominal complications with relatively narrow-spectrum antimicrobial agents, such as second-generation cephalosporins. In the present study, we aimed to retrospectively analyze the use of antimicrobial agents and the resulting treatment outcomes in patients with intra-abdominal complications after gastrectomy at our facility. Methods: We conducted a retrospective observational study of patients treated with antibiotic agents for intra-abdominal infectious complications after gastrectomy between 2011 and 2021. We determined the proportion of "initial treatment failures" associated with the initial administration of antibiotic agents for post-operative intra-abdominal complications. Results: Post-operative intra-abdominal infections were observed in 29 patients. Broad-spectrum antimicrobial agents were not administered. We successfully treated 19 patients. Initial treatment failure was observed in 10 patients, of whom five experienced failure due to bacterial resistance to the initial antimicrobial agent. All 10 patients who experienced initial treatment failure were discharged after drainage procedures or other treatments. There were no deaths due to post-operative complications. Cefmetazole was used as the initial antimicrobial agent in 27 of the 29 patients. Conclusions: Considering that all patients with post-gastrectomy intra-abdominal infections were successfully treated using relatively narrow-spectrum antimicrobial agents, and initial treatment failure due to antimicrobial-resistant pathogens was 17.2%, the use of narrow-range antimicrobial agents for intra-abdominal infections after gastrectomy can be deemed appropriate.

Purpose: To investigate the efficacy of laparoscopic surgery for rectal cancer in obese and older patients, who are often characterized by a higher prevalence of comorbidities and physical decline., Methods: This large-scale multicenter retrospective cohort study included 524 patients with a body mass index of 25 or higher who underwent either open or laparoscopic surgery for stage II or III rectal cancer between 2009 and 2013. We assessed the short-term outcomes and relapse-free survival by comparing these surgical modalities. The patients were stratified into 404 non-elderly (< 70 years) and 120 elderly (≥ 70 years) patients., Results: In both patient groups, laparoscopic surgery was associated with a significantly reduced blood loss (non-elderly: 41 vs. 545 ml; elderly: 50 vs. 445 ml) and shorter hospital stays (non-elderly: 10 vs. 19 days; elderly: 15 vs. 20 days) than open surgery. The overall complications and relapse-free survival showed no significant differences between the two surgical techniques in either age group. Additionally, the impact of the laparoscopic procedure on the relapse-free survival remained consistent between the age groups., Conclusion: Laparoscopic surgery offers short-term benefits for patients with obesity and rectal cancer compared to open surgery, regardless of age, without influencing the long-term prognosis., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Competing Interests: None

Background: Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL., Methods: This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis., Discussion: This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer., Trial Registration: jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023., (© 2024. The Author(s).)

Background: Chemokine signaling within the tumor microenvironment can promote tumor progression. Although CCR1 and CXCR2 on myeloid cells could be involved in tumor progression, it remains elusive what effect would be observed if both of those are blocked., Methods: We employed two syngeneic colorectal cancer mouse models: a transplanted tumor model and a liver metastasis model. We generated double-knockout mice for CCR1 and CXCR2, and performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type, Ccr1 -/- , Cxcr2 -/- or Ccr1 -/- Cxcr2 -/- mice., Results: Myeloid cells that express MMP2, MMP9 and VEGF were accumulated around both types of tumors through CCR1- and CXCR2-mediated pathways. Mice reconstituted with Ccr1 -/- Cxcr2 -/- BM exhibited the strongest suppression of tumor growth and liver metastasis compared with other three groups. Depletion of CCR1 + CXCR2 + myeloid cells led to a higher frequency of CD8 + T cells, whereas the numbers of Ly6G + neutrophils, FOXP3 + Treg cells and CD31 + endothelial cells were significantly decreased. Furthermore, treatment with a neutralizing anti-CCR1 mAb to mice reconstituted with Cxcr2 -/- BM significantly suppressed tumor growth and liver metastasis., Conclusion: Dual blockade of CCR1 and CXCR2 pathways in myeloid cells could be an effective therapy against colorectal cancer., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT)., Background: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown., Methods: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1170) were assigned to the continued-APT group, discontinued-APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued-APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications., Results: The rate of thromboembolic complications in the continued-APT group was substantially lower than that in the non-APT or discontinued-APT groups (0.5% vs 2.6% vs. 2.9%; P =0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT ( P <0.001) and chronic anticoagulant use ( P <0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued-APT groups (0.6% vs 3.3%; P =0.012)., Conclusions: APT discontinuation after elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sigmoid volvulus (SV) is an acute abdominal condition characterized by torsion of the sigmoid colon around the mesentery, and often results in intestinal obstruction that may progress to bowel ischemia, necrosis, or perforation. Although SV commonly occurs due to predisposing factors like anatomic variations, age-related motility disorders, chronic constipation, and neurologic diseases, its incidence following sigmoid colon cancer surgery has rarely been reported. Herein, we report a rare case of recurrent SV following laparoscopic sigmoidectomy, which was successfully treated by laparoscopic redo surgery., Case Presentation: The patient was a 77-year-old man who had previously undergone laparoscopic sigmoidectomy for sigmoid colon cancer. Sixteen months postoperatively, he developed an incisional hernia at the umbilical site, which was treated with a laparoscopic repair using an intraperitoneal onlay mesh. After the hernia surgery, the patient had no anastomotic leakage or stenosis on regular follow-ups. However, 65 months after the first surgery, he presented with abdominal pain and distension. A computed tomography revealed that the remnant sigmoid colon was distended in a twisting manner around the anastomosis, leading to the diagnosis of SV. Although endoscopic de-torsion was successful, the SV recurred 2 months later, requiring elective laparoscopic redo surgery. The procedure involved resection of the sigmoid colon including the prior anastomosis with a left pararectal incision and DST re-anastomosis using a 25-mm circular stapler. The operation lasted 165 min with minimal bleeding and no complications. The postoperative course was uneventful. Pathological analysis confirmed fibrosis without malignancy. The patient remains well without recurrence of SV and anastomotic stenosis more than 5 years after surgery., Conclusion: SV following sigmoid colon cancer surgery has rarely been reported. This case illustrates the potential need for prophylaxis against postoperative SV, especially in patients with long sigmoid colon undergoing laparoscopic surgery for colorectal cancer. Further, laparoscopic redo surgery following initial laparoscopic surgery for colorectal cancer can be performed with minimal invasiveness, especially if patient selection is properly managed., (© 2024. The Author(s).)

A 79-year-old man presented with respiratory distress associated with a mediastinal mass and pleural effusion, and was diagnosed as having adult T-cell leukemia/lymphoma. The patient was highly refractory to anticancer drugs and radiotherapy from the time of onset and had progressive respiratory deterioration. However, his condition became stable with the administration of valemetostat for 11 days, and subsequent low-dose-anticancer agents led to a rapid improvement accompanied by high fever and a surge in C-reactive protein. In this case, the in vivo priming effect of valemetostat on tumor cells may have increased the sensitivity of these cells to conventional anti-cancer drugs., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal "tip" remnants., Case Presentation: The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively., Conclusions: If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up., (© 2024. The Author(s).)

The prognosis for patients with hepatocellular carcinoma (HCC) with extrahepatic metastasis remains poor. In recent years, the combination therapy of atezolizumab plus bevacizumab (ATZ/BEV) has demonstrated remarkable antitumor efficacy against HCC. Conversion surgery following chemotherapy emerges as a promising strategy for initially unresectable HCC. A 74-year-old man was referred to our department with disseminated HCC in the rectovesical pouch. He underwent hepatic subsegmental resection for primary HCC with abdominal wall invasion on the background of chronic hepatitis B 7 years ago. Intrahepatic recurrence was emerged 5 and 2 years ago, which was successfully managed with transarterial chemoembolization and radiofrequency ablation, respectively. Subsequently, 4 cm peritoneal dissemination appeared in the rectovesical pouch, invading the rectum, right pelvic neural plexus, and right seminal vesicle. ATZ/BEV therapy was initiated, but bevacizumab had to be discontinued due to fistula formation between the rectum and the tumor after two courses, and atezolizumab monotherapy was continued. After 1 year of ATZ/BEV combined therapy followed by atezolizumab monotherapy, the disseminated tumor, though still visible, exhibited a significant reduction, with no new intra- or extrahepatic lesions. To confirm the absence of other disseminated lesions, a diagnostic laparoscopy was performed. Subsequently, robot-assisted extended rectal anterior resection with the right seminal vesicle and right pelvic neural plexus, and permanent colostomy (Hartmann's procedure) were performed. Histopathological examination revealed disseminated HCC with a 4 mm resection margin to achieve R0 resection. We present a case of disseminated HCC successfully undergoing curative surgery through robot-assisted extended rectal anterior resection following ATZ/BEV combined therapy., Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00688-0., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest to disclose., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Intensive localized therapy is promising for the treatment of rectal cancer. In Japan, chemoradiotherapy (CRT) and neoadjuvant chemotherapy (NAC) are used as preoperative treatments for this disease. Magnetic resonance imaging (MRI) is used to diagnose lateral pelvic node (LPN) metastases, but the changes in LPN findings on MRI following preoperative treatment are unclear. Furthermore, there may be patients in whom LPN dissection can be omitted after CRT/NAC., Methods: Patients who underwent total mesorectal excision with LPN dissection after CRT/NAC at 13 Japanese Society for Cancer of the Colon and Rectum member institutions between 2017 and 2019 were included. Changes in the short diameter of the LPNs after CRT/NAC and the reduction rate were examined., Results: A total of 101 LPNs were examined in 28 patients who received CRT and 228 in 47 patients who received NAC. Comparison of LPNs before and after CRT/NAC showed that most LPNs shrank after CRT but that the size reduction was variable after NAC. Although some LPNs with a short diameter of <5 mm showed residual metastasis, no metastases were observed in LPNs that were <5 mm in short diameter before and after CRT/NAC and did not shrink after treatment., Conclusion: Although the short diameter of LPNs was significantly reduced by both CRT and NAC, even LPNs with a short diameter of <5 mm could have residual metastases. However, dissection may be omitted for LPNs <5 mm in short diameter that do not shrink after preoperative CRT or NAC., Competing Interests: Authors declare no conflict of interests for this article., (© 2024 The Author(s). Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background: Most intraoperative adverse events (iAEs) result from surgeons' errors, and bleeding is the majority of iAEs. Recognizing active bleeding timely is important to ensure safe surgery, and artificial intelligence (AI) has great potential for detecting active bleeding and providing real-time surgical support. This study aimed to develop a real-time AI model to detect active intraoperative bleeding., Methods: We extracted 27 surgical videos from a nationwide multi-institutional surgical video database in Japan and divided them at the patient level into three sets: training (n = 21), validation (n = 3), and testing (n = 3). We subsequently extracted the bleeding scenes and labeled distinctively active bleeding and blood pooling frame by frame. We used pre-trained YOLOv7&#95;6w and developed a model to learn both active bleeding and blood pooling. The Average Precision at an Intersection over Union threshold of 0.5 (AP.50) for active bleeding and frames per second (FPS) were quantified. In addition, we conducted two 5-point Likert scales (5 = Excellent, 4 = Good, 3 = Fair, 2 = Poor, and 1 = Fail) questionnaires about sensitivity (the sensitivity score) and number of overdetection areas (the overdetection score) to investigate the surgeons' assessment., Results: We annotated 34,117 images of 254 bleeding events. The AP.50 for active bleeding in the developed model was 0.574 and the FPS was 48.5. Twenty surgeons answered two questionnaires, indicating a sensitivity score of 4.92 and an overdetection score of 4.62 for the model., Conclusions: We developed an AI model to detect active bleeding, achieving real-time processing speed. Our AI model can be used to provide real-time surgical support., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Older patients with cancer are less likely to express their treatment preferences than younger patients. Question prompt lists (QPLs) facilitate communication between patients and physicians. Geriatric assessment (GA) is recommended when older patients with cancer make treatment decisions. This study estimated the effect size of a shared decision-making (SDM) support program combining QPLs with GA in terms of patients' subjective evaluation of the SDM process for a future definitive randomized controlled trial. We also evaluated the number and quality of aging-related communication during consultations, and feasibility and acceptability of the study for exploratory purposes., Materials and Methods: This is a pilot study with randomized allocation and blind evaluation. Patients aged 65 years or older at the National Cancer Center Hospital, Tokyo, Japan, scheduled to discuss the changes of their treatment, were randomly assigned in a 1:1 ratio to the SDM support program or usual care. This program consisted of 30-60 min of face-to-face coaching, with QPLs and GA provided before the coaching. As the primary endpoint, the decisional conflict scores given by the patients immediately after the consultation were compared between the two groups. For the secondary endpoints, the number and quality of aging-related communications during the consultations were assessed by evaluators (blinded) using audio-recordings. Adherence, burden, and usefulness were assessed for evaluating feasibility and acceptability of the SDM support program., Results: Forty patients were enrolled. All patients completed the GA questionnaire, for which 70% did not require any individual assistance. Answering the questionnaires took approximately 11 min. The decisional conflict scores were mean [standard deviation (SD)]: 19.3 [10.8] vs. 18.0 [11.1] (effect size: Cohen's d = 0.12) for the SDM support program and usual care groups, respectively. The number of aging-related communications during the consultation for the new treatment was higher in the SDM support program group than the usual care (mean [SD]: 3.3 [1.2] vs. 2.2 [1.5], effect size: cohen's d = 1.32). Patients felt that the SDM support program was useful but not burdensome or difficult., Discussion: The SDM support program was considered useful and feasible for older patients and able to facilitate communication regarding aging-related concerns., Trial Registration Number: The study protocol was registered on September 23, 2020, in the UMIN Clinical Trials Registry (UMIN000041867)., Competing Interests: Declaration of Competing Interest N. Boku received honorarium from Ono, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Taiho. Other authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Esophageal diverticulum is commonly associated with esophageal motility disorders, which can be diagnosed using high-resolution manometry (HRM) according to the Chicago classification. Although midesophageal diverticulum (M-ED) is associated with inflammatory processes, esophageal motility disorders have been recently identified as an etiology of M-ED., Case Presentation: We present the case of a patient with M-ED and elevated intrabolus pressure (IBP), which did not meet the criteria for esophageal motility disorders according to the Chicago classification. A 71-year-old man presented with gradually worsening dysphagia for two years and was diagnosed as having an 8-cm-long M-ED and multiple small diverticula in lower esophagus. HRM revealed a median integrated relaxation pressure of 14.6 mmHg, a distal latency of 6.4 s, and an average maximum IBP of 35.7 mmHg. He underwent thoracoscopic resection of the M-ED and myotomy, which successfully alleviated the symptoms and reduced the intrabolus pressure to normal levels., Conclusions: It is important to recognize the esophageal diverticulum pathology with HRM findings even in cases where the results may not meet the Chicago classification and to include myotomy based on the results., (© 2024. The Author(s).)

Background: Even in cancer of unknown primary (CUP), which is rare clinical condition, solitary anterosuperior lymph node (LN) along the common hepatic artery (No.8a LN) enlargement diagnosed as metastatic adenocarcinoma has never been reported., Case Presentation: A 68-year-old Japanese male, with a history of early gastric cancer that had been completely treated by endoscopic submucosal dissection 26 years ago, was detected a single enlarged nodule along the common hepatic artery, No.8a LN, incidentally by computed tomography performed for monitoring of interstitial pneumonia. Endoscopic ultra-sound-guided fine needle aspiration revealed that this nodule was adenocarcinoma suggestive of metastasis, but other imaging studies, including upper and lower gastrointestinal endoscopy, positron emission tomography, and ultrasonography did not detect any primary cancer. We have finally diagnosed as the LN metastasis of CUP and performed laparoscopic lymphadenectomy for this tumor. The tumor was approximately 5 cm in size, was in close proximity to the pancreas, and involved part of the right gastric artery and vein. LNs in the No.5 and No.8a areas, including this tumor, were dissected laparoscopically, and radical resection was achieved. The patient had no postoperative complication and was discharged on postoperative day 10. Immunohistopathological findings revealed that the tumor was poorly differentiated adenocarcinoma, and different from the histology of gastric cancer resected 26 years ago, although the tumor was suggestive of gastrointestinal origin. Imaging studies performed 2 and 6 months after discharge also did not reveal a primary site., Conclusion: We reported a case of solitary No.8a LN adenocarcinoma of CUP. For diagnostic and therapeutic purposes, radical resection is recommended for single enlarged intra-abdominal LN of CUP., (© 2024. The Author(s).)

Purpose: Esophagectomy is the primary surgical treatment for esophageal cancer, although other treatment approaches are often incorporated, including preoperative chemotherapy and chemoradiotherapy. The two major routes of esophageal reconstruction after esophagectomy are the anterior mediastinal (retrosternal, heterotopic) and posterior mediastinal (prevertebral, orthotopic) routes. However, which of these two routes of reconstruction is the most appropriate remains controversial. This systematic review aimed to compare the efficacy and safety of anterior mediastinal reconstruction with those of posterior mediastinal reconstruction after esophagectomy in esophageal cancer., Methods: In January 2022, a literature search of the CENTRAL, MEDLINE, and EMBASE databases was conducted to identify all published and unpublished randomized controlled trials, regardless of language. Eight studies were included for quantitative synthesis., Results: Postoperative death (9/129 and 4/125, risk ratio [RR]: 2.07, 95% confidence interval [CI]: 0.65-6.64) and incidence of anastomotic leak (24/208 and 26/208, RR: 0.95, 95% CI: 0.56-1.62) were not significantly different between the two mediastinal reconstructions. We could not perform a meta-analysis for quality of life, loss of body weight, or postoperative hospital stay due to data limitations., Conclusion: Overall, there was low-quality evidence to suggest that the outcomes of the anterior and posterior mediastinal routes of reconstruction are not significantly different in patients with esophageal cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Laparoscopic complete mesocolic excision with central vessel ligation has been widely accepted for its oncological benefits in colon cancer surgery. However, laparoscopic right hemicolectomy involves a risk for vascular injury during dissection around the surgical trunk. This technical difficulty has been attributed to the limited movement of conventional laparoscopic forceps. Although robotic devices can overcome the restricted motion of laparoscopic devices, they are not yet widely used. The ArtiSential is an articulating laparoscopic instrument that has a two-joint end-effector that enables a wide range of motion precisely reflecting the surgeon's finger movements, and is designed to compensate for the drawbacks of conventional laparoscopic tools. The present study demonstrated the utility of articulating instruments in laparoscopic right hemicolectomy by comparing the authors' laparoscopic procedures, using articulating instruments, with robotic procedures. Articulating laparoscopic instruments can be successfully maneuvered in virtually the same manner as robotic devices and, as such, represent a viable alternative to robotic surgery., Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00654-w., Competing Interests: Conflict of interestY.I., N.H. and K.O. have collaborative researches with LiveMed. The others have no conflict of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Liver injury associated with oxaliplatin (L-OHP)-based chemotherapy can significantly impact the treatment outcomes of patients with colorectal cancer liver metastases, especially when combined with surgery. To date, no definitive biomarker that can predict the risk of liver injury has been identified. This study aimed to investigate whether organoids can be used as tools to predict the risk of liver injury., Methods: We examined the relationship between the clinical signs of L-OHP-induced liver injury and the responses of patient-derived liver organoids in vitro. Organoids were established from noncancerous liver tissues obtained from 10 patients who underwent L-OHP-based chemotherapy and hepatectomy for colorectal cancer., Results: Organoids cultured in a galactose differentiation medium, which can activate the mitochondria of organoids, showed sensitivity to L-OHP cytotoxicity, which was significantly related to clinical liver toxicity induced by L-OHP treatment. Organoids from patients who presented with a high-grade liver injury to the L-OHP regimen showed an obvious increase in mitochondrial superoxide levels and a significant decrease in mitochondrial membrane potential with L-OHP exposure. L-OHP-induced mitochondrial oxidative stress was not observed in the organoids from patients with low-grade liver injury., Conclusions: These results suggested that L-OHP-induced liver injury may be caused by mitochondrial oxidative damage. Furthermore, patient-derived liver organoids may be used to assess susceptibility to L-OHP-induced liver injury in individual patients., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)