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Abstract 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/m2) on day 1 and two divided doses oral capecitabine (2000 mg/m2/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.

Abstract We developed a novel clamping device for laparoscopic surgery, free from conventional pinch structure, capable of uniformly occluding any ductal organ. This study aimed to evaluate performance of the new clamper compared to the pinch-type clamper. The new clamper consists of two metal bars with ties at each end, which enables parallel clamping. A resected porcine stomach was used, with an infusion tube at the anal end to increase intra-luminal pressure. The oral side of the stomach was clamped with either the new clamper or the pinch-type clamper, and their performances were evaluated in qualitative and semi-quantitative manner. Qualitative evaluation involved imaging the clamping site at intra-gastric pressures from 0 to 15 mmHg using microfocus computed tomography. The new clamper showed no gap even under increased intra-luminal pressure, while the pinch-type clamper showed a gap on the distal side. Quantitative evaluation measured bursting pressure under continuous air insufflation. Air leakages were observed in the new clamper at higher intra-luminal pressures than in the pinch-type clamper (46.1 mmHg vs. 13.6 mmHg, P

Abstract Background Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. Methods From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. Results Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). Conclusions This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.

Abstract 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.

Abstract Background Anorectal fistula cancer is often diagnosed in an advanced state, and radical resection is difficult when invasion of the pelvic wall is observed. In addition, there is currently no clear evidence for perioperative treatment of locally advanced cases. We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn’s disease, which was curatively resected after preoperative chemoradiotherapy. Case presentation A 49-year-old man who had been diagnosed with Crohn’s disease (ileocolonic type) at the age of 25 and was found to have an anorectal fistula and perianal abscess at the age of 44 was referred to our department with complaints of abdominal pain and diarrhea. Computed tomography (CT) showed anal stenosis due to a pelvic mass. Pathological analysis of a biopsy taken under general anesthesia indicated mucinous carcinoma. Magnetic resonance imaging (MRI) revealed infiltration into the prostate, seminal vesicles, levator ani muscle, and left internal obturator muscle, and the patient was diagnosed with cT4N0M0 cStage IIIB anorectal fistula cancer (UICC TNM classification 8th edition). After performing a laparoscopic sigmoid colostomy, chemoradiation therapy (capecitabine + oxaliplatin, 50.4 Gy/28fr) was initiated. The patient then underwent laparoscopic total pelvic exenteration, colonic conduit diversion, extensive perineal resection, and reconstruction using bilateral gluteus maximus flaps and a right rectus abdominis musculocutaneous flap. The pathological diagnosis was mucinous adenocarcinoma, pT4, and all margins were negative. No recurrence was evident 6 months after the operation without adjuvant chemotherapy. Conclusion We described a case of curative resection after preoperative chemoradiotherapy for anorectal fistula cancer with extensive invasion that was diagnosed during the course of Crohn’s disease.An accumulation of cases is needed to determine the usefulness of preoperative chemoradiation therapy for local control of anorectal fistula cancer associated with Crohn’s disease.

Here we report a case of locally advanced rectal cancer with vaginal invasion, which was successfully resected via laparoscopic surgery using intraoperative indocyanine green (ICG) navigation to determine the vaginal cut line. Based on preoperative examinations, an 81-year-old female was diagnosed with locally advanced rectal cancer with vaginal invasion. After preoperative chemoradiotherapy, the lesion was judged to be resectable. During surgery, the gynecologist transvaginally injected ICG into the vaginal submucosa to determine the caudal margin of the vaginal invasion, and laparoscopically dissected under the near-infrared image of the stained area. Pathological analysis of the resection specimen revealed negative resection margins. One year after surgery, there has been no recurrence.

Abstract Background The overall risk of colorectal cancer in Crohn's disease (CD) is higher than in the general population, and CD‐associated cancer (CDAC) has poorer prognosis than sporadic cancer. Developing treatment strategies for improving the prognosis of CDAC, we evaluated the characteristics of CDAC according to the underlying disease behavior, namely stricturing and penetrating. Methods This multicenter retrospective study comprises 316 CDAC patients who underwent surgery between 1985 and 2019. Clinicopathological findings including disease behavior and oncological outcomes were investigated. Results There was no association between the preoperative course of CDAC patients and disease behavior; however, postoperative information revealed distinctly different characteristics between CDAC patients with stricturing behavior and those with penetrating behavior (stricturing with lymphatic invasion and peritoneal dissemination recurrence, and penetrating with histologically poorly differentiated and local recurrence). Oncological outcome of patients with CDAC was distinctly different according to disease behavior, as penetrating provided a poor outcome (overall survival [OS]: p = 0.02; relapse‐free survival [RFS]: p = 0.002) whereas stricturing had no effect. Furthermore, penetrating behavior was identified as one of the independent risk factors for poor OS and RFS (OS: hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.16–3.09, p = 0.01; RFS: HR 2.15, 95% CI 1.28–3.63, p = 0.004). Conclusions Our study highlights the different characteristics of CDAC according to the underlying disease behavior and substantiates the poor prognosis of CDAC patients with penetrating behavior. Treatment planning including screening, surgical procedures, and postoperative treatment, with awareness of these findings, may contribute to improved prognosis for CDAC patients.

Abstract Background Metastatic testicular cancer is rare. In particular, primary colorectal cancer rarely metastasizes to the testes. This study reports a case of testicular metastasis recurrence 9 years after the resection of a primary colorectal cancer and a simultaneous metastatic lung tumour. Case presentation A 69-year-old man underwent a laparoscopic left hemicolectomy for descending colon cancer. Preoperative computed tomography revealed a solitary left lung mass. Postoperative chemotherapy reduced the size of the lung mass, and 6 months after the primary resection, the patient underwent a left upper segmentectomy. Based on the pathological examination, he was diagnosed with pulmonary metastasis from colorectal cancer. After four courses of adjuvant chemotherapy, the patient was recurrence-free. However, 9 years and 6 months after the primary resection, he complained of discomfort in his left testicle. Physical examination revealed a left testicular mass. Since a malignancy was not excluded via imaging, left testicular resection was performed to confirm the diagnosis. The pathological diagnosis was testicular metastasis from colorectal cancer. The patient was followed up without medication, and remained healthy, without recurrence, 11 months postoperatively. Conclusions It is important to follow up with testicular metastasis in mind, although it is rare.

Abstract Approximately 10% of patients with colorectal cancer with submucosal invasion have lymph node metastasis. Pathological risk factors for lymph node metastasis have varying sensitivities and specificities. To predict the risk of lymph node metastasis, the identification of new risk factors is vital. Tumor-infiltrating T cells have been reported to improve the prognosis of many solid tumors. Therefore, the purpose of this study was to examine the relationship between lymph node metastasis and tumor-infiltrating T cells in patients with colorectal cancer with submucosal invasion. We examined CD8+ tumor-infiltrating T cells level as a risk factor for lymph node metastasis in patients with colorectal cancer with submucosal invasion. Using immunohistochemical staining, we identified CD8 + T cells in surgically resected specimens from 98 patients with SM-CRC. We showed that low CD8+ tumor-infiltrating T cells levels are positively correlated with lymph node metastasis. Furthermore, by combining the number of CD8+ tumor-infiltrating T cell and the number of CD103+ tumor-infiltrating T cells, the results showed a high positive predictive value for lymph node metastasis in cases with low numbers of both types of tumor-infiltrating T cells and a high negative predictive value in cases with high numbers of both types of tumor-infiltrating T cells.

Summary: Somatic cell reprogramming using the microRNAs miR-200c, miR-302s, and miR-369s leads to increased expression of cyclin-dependent kinase inhibitors in human colorectal cancer (CRC) cells and suppressed tumor growth. Here, we investigated whether these microRNAs inhibit colorectal tumorigenesis in CPC;Apc mice, which are prone to colon and rectal polyps. Repeated administration of microRNAs inhibited polyp formation. Microarray analysis indicated that c-MAF, which reportedly shows oncogene-like behavior in multiple myeloma and T cell lymphoma, decreased in tumor samples but increased in microRNA-treated normal mucosa. Immunohistochemistry identified downregulation of c-MAF as an early tumorigenesis event in CRC, with low c-MAF expression associated with poor prognosis. Of note, c-MAF expression and p53 protein levels were inversely correlated in CRC samples. c-MAF knockout led to enhanced tumor formation in azoxymethane/dextran sodium sulfate–treated mice, with activation of cancer-promoting genes. c-MAF may play a tumor-suppressive role in CRC development.

Abstract Background The standard treatment for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, it has been suggested that intensification of neoadjuvant treatment with polychemotherapy in addition to CRT instead of as an adjuvant chemotherapy is better tolerated and associated with a higher pathological complete response (pCR) rate. This concept is known as total neoadjuvant therapy (TNT). Recently, the addition of immunotherapy to preoperative CRT has been reported to be useful in LARC patients with mismatch-repair-deficiency and high levels of microsatellite instability (MSI-H), but there are no reports showing the therapeutic effect of nivolumab in combination with TNT. Case presentation A 23-year-old man had frequent diarrhea. Preoperative examination revealed two adenocarcinomas in the rectum. His maternal grandmother had a rectal cancer patient who developed the disease at age 70s. The larger tumor was located at the peritoneal reflection, and its anterior border close to the prostate (

Abstract Background Low anterior resection syndrome (LARS) is the most common complication after rectal cancer resection. We aimed to identify LARS' predictive factors and construct and evaluate a predictive model for LARS. Methods This retrospective study included patients with rectal cancer more than 1 year after laparoscopic or robotic-assisted surgery. We administered a questionnaire to evaluate the degree of LARS. In addition, we examined clinical characteristics with univariate and multivariate analysis to identify predictive factors for major LARS. Finally, we divided the obtained data into a learning set and a validation set. We constructed a predictive model for major LARS using the learning set and assessed the predictive accuracy of the validation set. Results We reviewed 160 patients with rectal cancer and divided them into a learning set (n = 115) and a validation set (n = 45). Univariate and multivariate analyses in the learning set showed that male (odds ratio [OR]: 2.88, 95% confidence interval [95%CI] 1.11–8.09, p = 0.03), age

Abstract Background Despite advances in medical treatments, most patients with Crohn's disease (CD) will still require surgery, with 20%‐50% needing redo surgery within 10 years after the primary procedure. There is no consensus on the application of laparoscopic redo surgery for recurrent CD. Methods This study included 107 patients with CD who underwent surgery from 2012 to 2020 at Osaka University Hospital. All procedures were laparoscopic. Patients were grouped based on whether the surgery was redo or primary for evaluation of the safety and feasibility of laparoscopic redo surgery. Results The study included 40 patients undergoing redo surgery and 67 having primary surgery. The median age at the time of the procedure was higher for those undergoing redo surgery (43 years vs 34 years, P

Abstract Aim Early detection of surgical site infection (SSI) allows for appropriate management after Crohn's disease (CD) surgery. The aim of this study was to evaluate the usefulness of bacterial culture of postoperative drainage fluid after CD surgery. Methods This study included 110 patients with CD who underwent surgery with bowel resection between January 2010 and March 2020 at Osaka University Hospital. Patients with only perianal surgery or incomplete records were excluded. Risk factors for SSI were evaluated in the context of clinical findings, including bacterial culture of postoperative drainage fluid, and bacterial species related to SSI were also examined. Results Of 110 patients, 18 (16.4%) developed SSI. Organ/space SSI developed in six, and a positive bacterial culture of drainage fluid (D‐Posi) was found in five (83.3%). Of 104 patients without organ/space SSI, 31 (29.8%) were D‐Posi (P = .027). Similarly, 68.8% with incisional SSI were D‐Posi, whereas 26.6% without incisional SSI were D‐Posi (P = .0021). Multivariate analysis revealed that D‐Posi was an independent risk factor in both organ/space and incisional SSI. Bacterial examination showed that Pseudomonas aeruginosa and Enterococcus faecalis were significantly detected in patients with SSI. Conclusion This study suggests the usefulness of postoperative drainage fluid bacterial culture for early diagnosis of SSI after CD surgery.

Abstract Background Stoma outlet obstruction (SOO) is much more common after total proctocolectomy (TPC) and ileal‐pouch anal anastomosis (IPAA) for ulcerative colitis (UC) compared to after rectal surgery for cancer. Few prior reports have evaluated anatomical risk factors for SOO. In this study we aimed to clarify the risk factors for SOO after IPAA, focusing on the anatomical perspective. Methods This study included 68 UC patients who underwent IPAA with diverting ileostomy. These cases were analyzed based on clinicopathological factors and computed tomography (CT)‐based anatomical factors. Results SOO was identified in 18 patients (26.5%). We compared this SOO group with the non‐SOO group. The two groups significantly differed in sex distribution, and patients in the SOO group tended to have a longer postoperative hospital stay. Regarding surgery‐related factors, patients who underwent two‐stage surgery and experienced high‐output syndrome tended to develop SOO. Analysis of anatomical risk factors revealed that SOO was more common in patients with a longer distance between the root of their superior mesenteric artery and the bottom of the external anal sphincter (rSMA‐bEAS). This tendency remained significant even with adjustment for patient height. In multivariate analyses, adjusted rSMA‐bEAS (>191.0 mm/m) and male sex were independent risk factors associated with SOO. Conclusion A long rSMA‐bEAS distance suggests that the mesentery is likely to be under tension. In such cases, surgeons should endeavor to avoid tension in the mesentery as much as possible.

Abstract Background The population is aging rapidly, and the population of patients who undergo surgeries is aging, too. Elderly patients have much risk of postoperative delirium, which increases the number of adverse events. The aim of this study was to investigate the risk factors of postoperative delirium in elderly patients with colorectal cancer. Methods We conducted a retrospective cohort analysis of consecutive patients aged 70 years and older who underwent surgeries for colorectal cancer at our department in the period from May 2012 to October 2019. We investigated the correlation between the incidence of postoperative delirium and Comprehensive Geriatric Assessment (CGA) scores, comorbidities, and perioperative factors. Postoperative delirium was retrospectively diagnosed by checking clinical records. Results Postoperative delirium was diagnosed in 36 of 271 patients (13.3%) with colorectal cancer. Among many comorbidities, only renal disease was significantly associated with postoperative delirium. Among the items in the CGA, age; Mini‐Mental State Exam (MMSE), Barthel Index, Instrumental Activities of Daily Living (IADL), Vitality Index, and Geriatric Depression Scale (GDS) scores; and grip strength were associated with postoperative delirium. Among perioperative factors, blood transfusion was associated with postoperative delirium. Multivariate logistic regression analysis identified older age, MMSE, GDS, and grip strength as significant independent risk factors for postoperative delirium. Conclusions This single‐center retrospective observational study demonstrated that grip strength is an independent predictor of postoperative delirium, along with age, MMSE, and GDS.

Abstract Background The incidence of fecal incontinence is ~2%, and the associated symptoms significantly impact daily life. New treatment methods including electrical stimulation and regenerative therapy using stem cells for fecal incontinence have been reported. We explored the usefulness of an anal sphincter injury mouse model by means of a balloon catheter and focused on the defecation status of mice as a novel method for evaluating anal function. We examined the utility of the mouse model of anal sphincter injury and the efficacy of electrical stimulation as a treatment modality using this model. Methods A 10‐mm balloon catheter was used to create an anal sphincter injury model in mice. Sphincter function was evaluated in the noninjured (n = 4), injured (n = 4), noninjured electrical stimulation (n = 4), and injured electrical stimulation (n = 4) groups. Defecation status (defecation frequency in 24 h and fecal weight per stool) and pathological evaluation were used for comparison. Results The defecation frequency increased and the fecal weight per stool decreased significantly in the anal sphincter injury model. Pathological evaluation revealed that anal sphincter tears occurred the day after the injury. Meanwhile, the defecation frequency improved on d 7, and the fecal weight per stool gradually normalized to that of the control group and exhibited significant sphincter muscle hypertrophy in the electrical stimulation group. Conclusion Anal sphincter injury using a balloon catheter in mice allowed us to create a uniform model. The evaluation of defecation status in mice is a useful method for comparatively evaluating anal function.

The novel coronavirus disease 2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread at a very fast rate, overwhelming and disrupting healthcare systems around the world since its outbreak in December 2019 in China. As of October 2021, the total number of COVID-19 cases exceeds 240,000,000, and the total number of deaths is close to 5,000,000. In the situation of widespread SARS-CoV-2 infection, restrictions on the medical system due to shifts in medical care to accommodate the pandemic will occur, and its impact on surgical and endoscopic treatment for colorectal cancer is inevitable. Therefore, it is necessary to satisfy all of the following requirements: patient safety, prevention of exposure of healthcare workers including surgeons, prevention of nosocomial infection, and a decision on how to treat the primary disease. Surgical triage is also required, based on comprehensive consideration of the patient's condition, the severity of the disease, the SARS-CoV-2 infection situation in the region, and the medical supply system at each facility, including medical resources, human resources, and the availability of medical equipment. Understanding the diagnostic and treatment environment that the COVID-19 pandemic has dramatically changed is important in providing appropriate surgical care to patients who require surgery while taking utmost care to prevent the spread of COVID-19.

Antigen-presenting cells, including macrophages and dendritic cells, are a type of innate immune cells that can induce the differentiation of T cells and activate the adaptive immune response. In recent years, diverse subsets of macrophages and dendritic cells have been identified in the intestinal lamina propria of mice and humans. These subsets contribute to the maintenance of intestinal tissue homeostasis by regulating the adaptive immune system and epithelial barrier function through interaction with intestinal bacteria. Further investigation of the roles of antigen-presenting cells localized in the intestinal tract may lead to the elucidation of inflammatory bowel disease pathology and the development of novel treatment approaches.

Abstract Epithelial–mesenchymal transition (EMT) is a drastic phenotypic change during cancer metastasis and is one of the most important hallmarks of aggressive cancer. Although the overexpression of some specific transcription factors explains the functional alteration of EMT-induced cells, a complete picture of this biological process is yet to be elucidated. To comprehensively profile EMT-related genes in colorectal cancer, we quantified the EMT induction ability of each gene according to its similarity to the cancer stromal gene signature and termed it “mesenchymal score.” This bioinformatic approach successfully identified 90 candidate EMT mediators, which are strongly predictive of survival in clinical samples. Among these candidates, we discovered that the neuronal gene ARC, possibly originating from the retrotransposon, unexpectedly plays a crucial role in EMT induction. Profiling of novel EMT mediators we demonstrated here may help understand the complexity of the EMT program and open up new avenues for therapeutic intervention in colorectal cancer.

Abstract Background The presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis. Methods Eighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination. Results Of the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity. Conclusions The cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.

Abstract Aim Many inflammation‐nutrition scores, including the Glasgow Prognostic Score (GPS), have been reported as prognostic biomarkers in patients with colorectal cancer (CRC). We aimed to examine the predictive ability of the GPS and to improve the GPS. Methods We included a total of 438 patients with stage 0‐III CRC who underwent curative surgery from 2010 to 2013. They were divided into a training set comprising 221 patients and a validation set comprising 227 patients, according to the date of surgery. In the training set, the GPS was verified using a Cox regression model, and cut‐off values for C‐reactive protein (CRP) and albumin for relapse‐free survival (RFS) were calculated using receiver operating characteristics (ROC) curves. The improved GPS (iGPS) was developed with additional optimal cut‐off values. We also compared the iGPS with the conventional GPS in the validation set. Results The high GPS (GPS: 1‐2) was correlated with RFS and overall survival (OS) in the training set. Cut‐off values of CRP and albumin for RFS were 1.6 and 3.9, and we modified the GPS accordingly, adding the cut‐off values of 2 and 3.9 to CRP and albumin, respectively. In the validation set, a high iGPS was an independent prognostic factor for RFS (hazard ratio [HR]: 2.273; 95% confidence interval [CI]: 1.212‐4.364; P = .011), although the conventional GPS was not. Conclusion The iGPS was a more accurate prognostic predictor for patients with stage 0‐III CRC.

Abstract Background Local recurrence is common after curative resections for rectal cancer. Surgical intervention is among the best treatment choices. However, achieving a negative resection margin often requires extensive pelvic organ resections; thus, the postoperative complication rate is quite high. Recent studies have reported that the inflammatory index could predict postoperative complications. This study aimed to validate the correlation between clinical factors, including inflammatory markers, and severe complications after surgery for local recurrent rectal cancer. Methods This retrospective study included 99 patients that underwent radical resections for local recurrences of rectal cancer. Postoperative complications were graded according to the Clavien-Dindo classification. Grades ≥3 were defined as severe complications. Risk factors for severe complications were identified with univariate and multivariate logistic regression models and assessed with receiver-operating characteristic curves. Results Severe postoperative complications occurred in 38 patients (38.4%). Analyses of correlations between inflammatory markers and severe postoperative complications revealed that the strongest correlation was found between the prognostic nutrition index and severe postoperative complications. The receiver-operating characteristic analysis showed that the optimal prognostic nutrition index cut-off value was 42.2 (sensitivity: 0.790, specificity: 0.508). In univariate and multivariate analyses, a prognostic nutrition index ≤44.2 (Odds ratio: 3.007, 95%CI:1.171–8.255, p = 0.02) and a blood loss ≥2850 mL (Odds ratio: 2.545, 95%CI: 1.044–6.367, p = 0.04) were associated with a significantly higher incidence of severe postoperative complications. Conclusions We found that a low preoperative prognostic nutrition index and excessive intraoperative blood loss were risk factors for severe complications after surgery for local recurrent rectal cancer.

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. It is reported that TGF-β/Smad signal pathway is inactivated in patients with Crohn’s disease by overexpression of Smad 7. With expectation of multiple molecular targeting by microRNAs (miRNAs), we currently attempted to identify certain miRNAs that activate TGF-β/Smad signal pathway and aimed to prove in vivo therapeutic efficacy in mouse model. Through Smad binding element (SBE) reporter assays, we focused on miR-497a-5p. This miRNA is common between mouse and human species and enhanced the activity of TGF-β/Smad signal pathway, decreased Smad 7 and/or increased phosphorylated Smad 3 expression in non-tumor cell line HEK293, colorectal cancer cell line HCT116 and mouse macrophage J774a.1 cells. MiR-497a-5p also suppressed the production of inflammatory cytokines TNF-α, IL-12p40, a subunit of IL-23, and IL-6 when J774a.1 cells were stimulated by lipopolysaccharides (LPS). In a long-term therapeutic model for mouse dextran sodium sulfate (DSS)-induced colitis, systemic delivery of miR-497a-5p load on super carbonate apatite (sCA) nanoparticle as a vehicle restored epithelial structure of the colonic mucosa and suppressed bowel inflammation compared with negative control miRNA treatment. Our data suggest that sCA-miR-497a-5p may potentially have a therapeutic ability against IBD although further investigation is essential.

Objectives: In the 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC), ovarian metastasis is classified as distant metastasis. We assessed the significance of resection of ovarian metastases and the validity of this 9th edition of JCCRC for ovarian metastases from colorectal cancer (CRC). Methods: We retrospectively analyzed the clinicopathological factors and overall survival of 17 patients with ovarian metastases from CRC who underwent resection and 110 female CRC patients with Stage IV (M1a) disease. Results: The patients with only ovarian metastases who underwent resection had a longer median survival time than patients with both ovarian and peritoneal metastases who underwent resection (45.4 months vs. 9.3 months, P = 0.029). The 5-year overall survival of the patients with only ovarian metastases who underwent R0 resection was as long as that of the female Stage IV (M1a) CRC patients after R0 resection (50% vs. 48%, P = 0.334). Conclusions: We found that, after resection, patients with only ovarian metastases had significantly better prognoses than patients with ovarian and peritoneal metastases. R0 resection of ovarian metastasis indicated as good prognosis as R0 resection of metastasis to one distant organ without ovaries. So the 9th edition of JCCRC, which classifies ovarian metastasis from CRC as distant metastasis, is appropriate.

Abstract Malnutrition has been considered to be associated with the prognosis of cancer. The Geriatric Nutritional Risk Index (GNRI), based on serum albumin levels, present body weight, and ideal body weight, is a simple screening tool to predict the risk of nutrition-related morbidity and mortality in elderly patients. We aimed to evaluate whether preoperative GNRI was associated with postoperative complications and prognosis in elderly patients with colorectal cancer (CRC). We retrospectively enrolled 313 CRC patients aged ≥65 years after curative surgery and classified them into an all-risk GNRI (≤98) group and a no-risk GNRI (>98) group. Kaplan-Meier analysis showed overall survival was significantly worse in the all-risk GNRI group than in the no-risk GNRI group (P = 0.009). Multivariable analyses showed low GNRI (≤98) was an independent risk factor for postoperative complications (P = 0.048) and overall survival (P = 0.001) in the patients. Among the complications, the incidence of surgical site infection, in particular, was significantly higher in the all-risk GNRI group (P = 0.008). In conclusion, low preoperative GNRI (≤98) was associated with increased postoperative complications and poor prognosis. Preoperative GNRI can be used as an identifier for potential high-risk group of morbidity and mortality in elderly CRC patients.

Abstract Background In pelvic surgery, it is important to anticipate potential anatomic variations, which may be unknown, and inter-relationships among intrapelvic vessels. Here, we comprehensively analyzed intrapelvic vessel patterns. Method This retrospective analysis included 81 patients that underwent colorectal surgery in our institution in 2016. A total of 162 half-pelvises were imaged with contrast-enhanced computed tomography. We scrutinized thin-slice images. Results We found variations in the number of internal iliac veins. In 47.5% of cases, one internal iliac vein drained into the ipsilateral common iliac vein in both halves of the pelvis. In the other cases, several internal iliac veins were observed in one or both halves of the pelvis. We analyzed the inter-relationships between the superior gluteal artery and the sacral nerve plexus in pelvic halves. Superior gluteal arteries ran between the 5th lumbar nerve and 1st sacral nerves, in 82% of halves, and lateral to the 5th lumbar nerve, in 17% of halves. Dorsally, the superior gluteal artery ran on the medial side of the internal iliac vein in 15% of halves. In 28% of half-pelvises, two superior gluteal veins were observed. Superior gluteal veins passed through the sacral nerve plexus lateral to 5th lumbar, between 5th lumbar and 1st sacral, and between 1st and 2nd sacral nerve, in 42.0, 47.5, and 37.7% of halves, respectively. We evaluated the rate of symmetric pelvic anatomies, and found that all anatomic variations formed symmetrically, except the number of internal iliac veins. Conclusion This study clarified the anatomical variations of intrapelvic vessels and their inter-relationships. These findings will benefit our understanding of pelvic anatomy and enhance the safety of radical surgery for treating pelvic diseases.

Abstract This review outlines current topics on the surgical treatment of benign colorectal diseases, with a focus on inflammatory bowel disease (IBD) and diverticulitis. Treatment options for IBD and diverticulitis have evolved in the last few years as a result of medical advances in technology and new clinical trials. Therefore, treatment options and strategies need to be updated to provide optimal care for patients. The purpose of this review is to elucidate recent global trends and update the surgical treatment strategy for IBD and diverticulitis based on literature published in the past 2 years. Prevalence of IBD, including ulcerative colitis and Crohn's disease, has increased over the last few decades. During this period, many new medical therapies were introduced for the treatment of IBD, including biological therapy, immunomodulators, and leukocyte apheresis therapy. As a result, new surgical strategies for IBD are required. In order to improve surgical outcomes in IBD patients, the influence of preoperative treatment on postoperative complications needs to be considered. The incidence of diverticulitis is also increasing with lifestyle changes and increasing numbers of older people. For diverticulitis with perforation and generalized peritonitis, surgery is the gold standard. Elective surgery after conservative treatment of diverticulitis is also an option because of high recurrence rates. With an increase in diverticulitis, systematic strategies are essential for an appropriate approach to diverticulitis, taking into account various factors, including the patient's background.

This study aimed to analyze circulating tumor cells (CTCs) from patients with colorectal cancer (CRC). We designed a dielectrophoresis-based micropore system and tested its cell capture with HT29 colon cancer cells. Then, blood samples were drawn from 24 patients with stages II-IV CRC. Mononuclear cells were isolated and loaded into the micropore system. Single cells were positioned into small pores with dielectrophoresis. After labeling the cells with the appropriate antibodies, tumor-like cells were collected with an automated micromanipulator. We collected 43 CTCs from 15 out of 24 patient samples. The presence of CTC was significantly associated with ling metastasis. We performed whole genome amplification, followed by PCR and Sanger sequencing, to examine the point mutations in the KRAS, BRAF, and PIK3CA genes. This mutation analysis was successfully performed in 35 cells. Among the 14 cytokeratin (CK)-positive cells, we found PIK3CA mutations in three cells (21%) from two patients. Among the 21 CK-negative cells, we found a KRAS mutation in one cell (5%) from one patient and a PIK3CA mutation in one cell (5%) from one patient. It is noteworthy that these mutations were not detected in the corresponding primary tumors. In conclusion, dielectrophoresis-based capture in a micropore system was useful for detecting both CK-positive and CK-negative CTCs. This simple method could be applied to various tumor types.

Abstract Background Intraductal papillary-mucinous neoplasms (IPMNs) are potentially malignant intraductal epithelial neoplasms that sometimes penetrate into other organs. To the best of our knowledge, no report has yet described a case with penetration into the spleen. We recently encountered a case of IPMN with penetration of the stomach and spleen that was successfully treated by total pancreatectomy. Case presentation A 70-year-old female visited our hospital with a complaint of fever and abdominal pain. Contrast-enhanced computed tomography (CT) revealed dilatation of the main pancreatic duct in the entire pancreas and penetration into the stomach and spleen. Upper gastrointestinal endoscopy revealed mucin extruding from four openings of the fistula in the stomach. No malignancy was detected based on cytology of the mucin. Inflammation markers and tumor markers (CEA, CA19–9) were elevated in the blood. The pre-operative diagnosis was IPMN of main pancreatic duct type penetrating into the stomach and spleen. A total pancreatectomy and splenectomy were performed, combined with distal gastrectomy including resection of the fistulas between the pancreas and stomach. No postoperative complications were noted. Histopathological examination of the resected specimen revealed atrophy of the pancreatic parenchyma, and the main duct of the pancreas was filled with mucin. Mucin-producing malignant tumor cells were detected in the epithelium of the main pancreatic duct with no signs of invasion. No malignancy was found at the fistulas between the pancreas and stomach or spleen. The patient was finally diagnosed with non-invasive intraductal papillary-mucinous carcinoma (IPMC) of main pancreatic duct type. Mechanical penetration was suspected as a mechanism of the penetration. The patient remained disease-free without evidence of recurrence more than 15 months after the operation. Conclusion Though IPMNs sometimes penetrate into other adjacent organs, penetration into two organs, including the spleen, is rare. The rare case of IPMC penetrating into the stomach and spleen presented here was treated successfully by total pancreatectomy.

Abstract Adequate blood flow in anastomosis is of paramount importance to prevent anastomotic leakage. However, it is sometimes difficult to predict the viability of the intestine during surgery. During left-sided colectomy, blood flow on the remnant distal bowel is supplied only from the middle and inferior rectal arteries. The blood backflow after the root ligation of the inferior mesenteric artery is often said to be kept up to promontorium levels; however, this premise is actually based on experience, without reliable evidence. Here, we introduce the intraoperative evaluation of blood flow on the remnant distal bowel during left-sided colectomy using an indocyanine green fluorescence technique.

Postoperative complications related to anastomosis, including postoperative anastomotic bleeding and anastomotic leakage, remain a serious issue. The effect of anastomotic devices on suture complications during intestinal anastomosis remains unclear. The present study examined the utility of automated anastomotic devices for reducing anastomotic complication risks. A retrospective cohort study of colorectal cancer surgeries in which an anastomosis device was used at Osaka University Hospital (Suita, Japan) between January 2018 and December 2022 was conducted. Cases of emergency surgery, inflammatory bowel disease and simultaneous surgery for other cancers were excluded. Experienced gastrointestinal surgeons performed manual anastomosis using the ETHICON Circular Stapler CDH or EEA Circular Stapler, and automatic anastomosis using the ECHELON CIRCULAR Powered Stapler, with no observed operator bias. Additionally, a meta-analysis that included other study results was performed. The outcomes included postoperative complications, mainly anastomotic leakage. The study included 414 patients: 231 in the manual circular stapler group and 183 in the powered circular stapler (PCS) group. Although this retrospective study found no statistically significant association between the anastomotic device used and anastomotic complications, an increased risk ratio was observed in the manual group compared with the automatic group when restricted to elderly patients. Similarly, a meta-analysis found a significantly higher anastomotic complication risk in the manual group compared with the automatic group (random-effects model; odds ratio, 0.376; 95% confidence interval, 0.232-0.610; P<0.0001). The findings of the present study suggested that a PCS is useful for reducing the anastomotic complication risk in patients undergoing colorectal cancer surgery. [ABSTRACT FROM AUTHOR]

The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated. Here, we show that GPR31, which is activated by the gut bacterial metabolite pyruvate, is specifically expressed on type 1 conventional dendritic cells (cDC1s) in the lamina propria of the human intestine. Using human induced pluripotent stem cell-derived cDC1s and a monolayer human gut organoid coculture system, we show that cDC1s extend their dendrites toward pyruvate on the luminal side, forming transepithelial dendrites (TED). Accordingly, GPR31 activation via pyruvate enhances the fundamental function of cDC1 by allowing efficient uptake of gut luminal antigens, such as dietary compounds and bacterial particles through TED formation. Our results highlight the role of GPCRs in tuning the human gut immune system according to local metabolic cues. [ABSTRACT FROM AUTHOR]

Background/Aim: Transanal endoscopic local excision requires fine operation in a very narrow space in the rectum. We report a case in which the use of surgical instruments with a multi-jointed structure allowed safe resection of a lesion with a stable field of view, resulting in preservation of postoperative function. Case Report: The patient was a 49-year-old man who had a rectal neuroendocrine tumor (NET) (G1) with erosive changes in the lower rectum. Preoperative imaging showed no evidence of surrounding lymph node or distant metastasis; thus, we performed a transanal endoscopic local excision of the tumor. After positioning the patient under general anesthesia and securing the field of view in the intra-rectal cavity, the flexion of the surgical instruments with a multi-jointed structure was used to secure the operating space to not interfere with the camera and the surgeon’s right hand. The operating field was developed, and the tumor was incised by stable traction. After the excision, the needle was advanced in the direction of the intestinal axis using the multi-jointed holder, and continuous suturing was performed. The patient has no recurrence without any defecation disorder. Conclusion: The use of multijointed surgical instruments in transanal endoscopic excision of rectal tumors can provide a stable operative field and preserve postoperative function. The advanced flexibility of these instruments allows precise manipulation in the narrow rectal space, resulting in successful tumor resection with minimal invasiveness and no postoperative complications. These findings suggest that multi-jointed instruments are valuable for enhancing the safety and efficacy of minimally invasive rectal surgery. [ABSTRACT FROM AUTHOR]

Background Pouch-related complications (PRCs), such as pelvic abscesses and perianal complex fistulas, can occur after ileal pouch–anal anastomosis (IPAA) in ulcerative colitis (UC). They are often difficult to treat and require salvage surgery. We report two cases of PRC associated with fistulas. Case presentation First case: A 38-year-old man was diagnosed with UC at age 26 years. Four months after the diagnosis of UC, the patient underwent hand-assisted laparoscopic restorative proctocolectomy, IPAA, and ileostomy for acute fulminant UC. Two years after the closure of the ileostomy, the patient developed a perianal abscess and underwent ileostomy reconstruction. He was referred to our department at 35 years of age, because his symptoms did not improve despite repeated seton drainage of a complicated perineal fistula. We diagnosed PRC with a pelvic abscess and complicated pouch fistula and performed salvage surgery. This diagnosis was revised to Crohn’s disease. Second case: A 50-year-old man was diagnosed with UC at age 18 years and was administered high doses of steroids; however, his symptoms did not improve. He underwent restorative proctocolectomy, IPAA, and ileostomy at another hospital. The ileostomy was closed, and his condition stabilized thereafter. At 35 years of age, perianal pain developed, and he was diagnosed with a complicated pouch–perineal fistula. A fistula was observed near the staple line of the ileal end closure on the head side of the pouch. Reconstruction of the ileostomy and seton drainage were performed; however, his symptoms did not improve, and he was referred to our hospital. We diagnosed PRC with a pelvic abscess and a complicated pouch fistula and performed salvage surgery. The resected specimen showed strictures in two locations: at the oral site of the afferent limb (at the pouch) and at the IPAA. Both patients returned to society and are currently outpatients. Conclusions We encountered two cases of PRC after IPAA that did not improve with seton drainage or ileostomy. Pouch resection was performed after considering the patient’s quality of life and reintegration into society. [ABSTRACT FROM AUTHOR]

Background/Aim: Intestinal malrotation (IM) often remains undetected until adulthood, being discovered during testing or surgery for other comorbidities. Preoperative understanding of this anatomical abnormality is crucial. Case Report: An 80-year-old woman presented with cecal cancer. Three-dimensional computed tomography (CT) revealed that the cecum was located at the midline of the abdominal cavity, the duodenum did not cross the midline, and the ileocolic vein ran to the left. Clinically diagnosed with stage IVc cecal cancer complicated by IM, the patient underwent laparoscopic surgery. The ascending colon and cecum were not fixed to the retroperitoneum. The duodenum lacked the second, third, and fourth portions and the small bowel was distributed on the left and right sides of the abdominal cavity. Adhesions had shortened the mesentery, which were released close to their normal positions. Conclusion: Although laparoscopic surgery is superior to open surgery in terms of securing the field of view in a narrow space, providing a magnifying effect, and minimal invasiveness, it has a limited field of view and is inferior in terms of grasping the overall anatomy, which may be disadvantageous in cases of anatomical abnormalities. Colorectal cancer with IM is rare; however, the rate of preoperative diagnosis seems to be increasing thanks to improvements in diagnostic imaging, such as three-dimensional CT scans. In this study, we also reviewed 49 cases of colorectal cancer associated with IM. [ABSTRACT FROM AUTHOR]

Background/Aim: Although certain treatment options exist for intestinal incontinence, none are curative. Adipose-derived stem cells (ADSCs) have emerged as promising therapeutic agents, but most preclinical studies of their effectiveness for anal function have used autologous or allogeneic ADSCs. In this study, the effectiveness, timing of administration, and required dosage of human ADSCs were investigated for clinical application. Materials and Methods: A 10-mm balloon catheter was used to induce anal sphincter injury in immunodeficient mice in the following experimental groups (n=4 per group): ADSC (injected ADSCs after injury), PBS (injected phosphate-buffered saline after injury), and control (uninjured). The effects of different timing (immediately after injection and 30 days following injury) and number of human ADSCs administered was compared among groups based on defecation status and pathological evaluation. Results: In terms of defecation status, groups receiving ≥1×104 human ADSCs after injection showed improvement. Pathological images showed that compared to the PBS group, the thinnest part of the sphincter was thicker for animals that received ≥1×104 human ADSCs, and fibrosis of the sphincter was notable in those treated with 1×103 human ADSCs or PBS. Furthermore, defecation status was improved by administration of human ADSCs, not only immediately after injury, but also at 30 days following injury. Conclusion: Human ADSC administration in a mouse model of anal sphincter injury was effective. Injection of ≥1×104 human ADSCs was the amount necessary to improve defecation status, an effect detected in both the acute and chronic phases. [ABSTRACT FROM AUTHOR]

In current clinical practice, several treatment methods, including neoadjuvant therapy, are being developed to improve overall survival or local recurrence rates for locally advanced rectal cancer. The response to neoadjuvant therapy is usually evaluated using imaging data collected before and after preoperative treatment or postsurgical pathological diagnosis. However, there is a need to accurately predict the response to preoperative treatment before treatment is administered. The present study used a deep learning network to examine colonoscopy images and construct a model to predict the response of rectal cancer to neoadjuvant chemotherapy. A total of 53 patients who underwent preoperative chemotherapy followed by radical resection for advanced rectal cancer at the Osaka University Hospital between January 2011 and August 2019 were retrospectively analyzed. A convolutional neural network model was constructed using 403 images from 43 patients as the learning set. The diagnostic accuracy of the deep learning model was evaluated using 84 images from 10 patients as the validation set. The model demonstrated a sensitivity, specificity, accuracy, positive predictive value and area under the curve of 77.6% (38/49), 62.9% (22/33), 71.4% (60/84), 74.5% (38/51) and 0.713, respectively, in predicting a poor response to neoadjuvant therapy. Overall, deep learning of colonoscopy images may contribute to an accurate prediction of the response of rectal cancer to neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]