Nutritional status indicators predict tolerability to adjuvant chemotherapy in patients with stage II/III rectal cancer undergoing neoadjuvant chemoradiotherapy.

INTRODUCTION: Adjuvant chemotherapy (AC) after radical surgery following preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) is now the standard of care. The identification of risk factors for the discontinuation of AC is important for further improvements in survival. We herein examined the prognostic impact of chemotherapy compliance and its relationship with the prognostic nutritional index (PNI) before surgery. MATERIALS AND METHODS: A total of 335 Stage II-III LARC patients who underwent preoperative CRT between 2003 and 2022 at the University of Tokyo Hospital were retrospectively reviewed. We excluded patients with recurrence during AC and those who had not received AC. The relationship between AC and long-term outcomes and that between PNI values and the duration of AC were examined. RESULTS: Thirty-one patients discontinued AC and 62 continued AC. Recurrence-free survival (RFS) was significantly shorter in patients who discontinued AC (p = 0.0056). The discontinuation of AC was identified as an independent risk factor for RFS (HR 2.24, p = 0.0233). Twenty-one patients were classified as having low PNI (less than 40), which correlated with an older age, low BMI, and incomplete AC. Low PNI was an independent risk factor for a shorter duration of AC (HR 2.53, p = 0.0123). CONCLUSION: The discontinuation of AC was related to poor RFS in patients with LARC undergoing preoperative CRT. Furthermore, a low PNI value was identified as a risk factor for a shorter duration of AC.

Minimally invasive versus open multivisceral resection for rectal cancer clinically invading adjacent organs: a propensity score-matched analysis.

BACKGROUND: Minimally invasive surgery (MIS), such as laparoscopic and robotic surgery for rectal cancer, is performed worldwide. However, limited information is available on the advantages of MIS over open surgery for multivisceral resection for cases clinically invading adjacent organs. PATIENTS AND METHODS: This was a retrospective propensity score-matching study of consecutive clinical T4b rectal cancer patients who underwent curative intent surgery between 2006 and 2021 at the University of Tokyo Hospital. RESULTS: Sixty-nine patients who underwent multivisceral resection were analyzed. Thirty-three patients underwent MIS (the MIS group), while 36 underwent open surgery (the open group). Twenty-three patients were matched to each group. Conversion was required in 2 patients who underwent MIS (8.7%). R0 resection was achieved in 87.0% and 91.3% of patients in the MIS and open groups, respectively. The MIS group had significantly less blood loss (170 vs. 1130 mL; p < 0.0001), fewer Clavien-Dindo grade ≥ 2 postoperative complications (30.4% vs. 65.2%; p = 0.0170), and a shorter postoperative hospital stay (20 vs. 26 days; p = 0.0269) than the open group. The 3-year cancer-specific survival rate, relapse-free survival rate, and cumulative incidence of local recurrence were 75.7, 35.9, and 13.9%, respectively, in the MIS group and 84.5, 45.4, and 27.1%, respectively, in the open group, which were not significantly different (p = 0.8462, 0.4344, and 0.2976, respectively). CONCLUSION: MIS had several short-term advantages over open surgery, such as lower complication rates, faster recovery, and a shorter hospital stay, in rectal cancer patients who underwent multivisceral resection.

Evaluation of anorectal function using real-time tissue elastography before and after preoperative chemoradiotherapy.

PURPOSE: This study aimed to clarify the relationship between changes in elasticity and anorectal function before and after chemoradiotherapy. METHODS: This is a single-center prospective cohort study (Department of Surgical Oncology, The University of Tokyo). We established a technique to quantify internal anal sphincter hardness as elasticity using transanal ultrasonography with real-time tissue elastography. Twenty-seven patients with post-chemoradiotherapy rectal cancer during 2019-2022 were included. Real-time tissue elastography with transanal ultrasonography was performed before and after chemoradiotherapy to measure internal anal sphincter hardness as "elasticity" (hardest (0) to softest (255); decreased elasticity indicated sclerotic changes). The relationship between the increase or decrease in elasticity pre- and post-chemoradiotherapy and the maximum resting pressure, maximum squeeze pressure, and Wexner score were the outcome measures. RESULTS: A decrease in elasticity was observed in 16/27 (59.3%) patients after chemoradiotherapy. Patients with and without elasticity decrease after chemoradiotherapy comprised the internal anal sphincter sclerosis and non-sclerosis groups, respectively. The maximum resting pressure post-chemoradiotherapy was significantly high in the internal anal sphincter sclerosis group (63.0 mmHg vs. 47.0 mmHg), and a majority had a worsening Wexner score (60.0% vs. 18.2%) compared with that of the non-sclerosis group. Decreasing elasticity (internal anal sphincter sclerosis) correlated with a higher maximum resting pressure (r = 0.36); no correlation was observed between the degree of elasticity change and maximum squeeze pressure. CONCLUSION: Internal anal sphincter sclerosis due to chemoradiotherapy may correlate to anorectal dysfunction.

Local excision versus radical surgery for anal squamous cell carcinoma: a multicenter study in Japan.

BACKGROUND: The standard treatment for anal squamous cell carcinoma is chemoradiation therapy (CRT), but there is a possibility of over-treatment for early-stage disease. cTisN0 and cT1N0 disease is currently indicated for local excision, but it is unclear whether the indication of local excision can be expanded to cT2N0 disease. METHODS: 126 patients with cTis-T2N0 anal cancer treated at 47 centers in Japan between 1991 and 2015 were included. Patients were first classified into the CRT group and surgical therapy group according to the initial therapy, and the latter was further divided into local excision (LE) and radical surgery (RS) groups. We compared prognoses among the groups, and analyzed risk factors for recurrence after local excision. RESULTS: The CRT group (n = 87) and surgical therapy group (n = 39) showed no difference in relapse-free survival (p = 0.29) and overall survival (p = 0.94). Relapse-free survival curves in the LE (n = 23) and RS groups (n = 16) overlapped for the initial 3 years, but the curve for the LE group went lower beyond (p = 0.33). By contrast, there was no difference in overall survival between the two groups (p = 0.98). In the LE group, the majority of recurrences distributed in locoregional areas, which could be managed by salvage treatments. Muscular invasion was associated with recurrence after local excision (hazard ratio: 22.91, p = 0.011). CONCLUSION: LE may be applied to selected patients with anal cancer of cTis-T2N0 stage. Given the high risk of recurrence in cases with muscular invasion, it may be important to consider close surveillance and additional treatment in such patients.

Essential anatomy for lateral lymph node dissection.

In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential.

Unexplained increases in serum carcinoembryonic antigen levels in colorectal cancer patients during the postoperative follow-up period: an analysis of its incidence and longitudinal pattern.

BACKGROUND: Carcinoembryonic antigen (CEA) monitoring facilitates the detection of recurrence in patients with colorectal cancer (CRC) after resection. False-positive CEA has been reported in CRC patients with certain comorbidities or smokers. However, limited information is currently available on the frequency of and changes in falsely elevated CEA levels in patients without these conditions. MATERIALS AND METHODS: We retrospectively examined CRC patients who underwent surgical resection at our hospital between 2001 and 2017, had no recurrence for at least five years, and were free of known factors that may increase CEA. Postoperative CEA levels were retrieved until 2 years before the last contact. For comparison, we similarly selected patients who developed recurrence after resection of CRC during the same period, and CEA levels at initial presentation, at nadir, and at the time of recurrence were reviewed. The patterns of elevated CEA (>5 ng/ml) were classified as transient, repeated, or persistent based on longitudinal changes. The relationships between CEA and carbohydrate antigen 19-9, transaminases, creatinine, and C-reactive protein were examined. RESULTS: CEA elevation occurred in 90 (20%) out of 446 eligible patients without recurrence at least once during the mean postoperative period of 50.5 months, whereas CEA was >5 ng/ml in 117 (53%) of 221 patients when they developed recurrence. Twenty-seven patients without recurrence showed a transient elevation in CEA, 45 repeated elevations, and 18 a persistent elevation; the frequency of a high preoperative CEA level increased in this order. The majority (98%) of false elevations ranged between 5 and 15 ng/ml. CEA was not associated with other laboratory data. CONCLUSIONS: Unexplained CEA elevations were observed in 20% of recurrence-free CRC patients after surgery, and were classified into three patterns based on longitudinal changes. A more detailed understanding of patient-specific fluctuations in CEA will prevent unnecessary imaging studies and reduce medical costs.

Limited information is currently available on the frequency of and changes in falsely elevated carcinoembryonic antigen (CEA) levels after surgery for colorectal cancer. Unexplained postoperative CEA elevations were detected in 20% of colorectal cancer patients. The patterns of these elevations were classified into transient, repeated, and persistent.

Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

BACKGROUND AND AIMS: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. METHODS: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. RESULTS: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. CONCLUSIONS: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.

Preoperative chemoradiotherapy using tegafur/uracil, oral leucovorin, and irinotecan (TEGAFIRI) followed by oxaliplatin-based chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: the study protocol for a phase II trial.

BACKGROUND: Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol. METHODS: Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery. DISCUSSION: Since previous findings showed a high percentage of grade 3-4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031210660.

Diverticular perforation of terminal ileum associated with chemotherapy for non-small cell lung carcinoma: a case report.

A 71-year-old man was diagnosed with advanced non-small cell lung carcinoma and treated with chemotherapy developed ileocecal diverticulitis three times over the last 2 months of receiving second-line treatment. During the fourth diverticulitis event, the patient presented with fever and abdominal pain, worsening after 5 days. Abdominal computed tomography showed ascites and intra-abdominal free air, suggesting bowel perforation with acute diffuse peritonitis. We performed emergency surgery; the surgical findings showed diverticulosis with perforated diverticula in the ileocecal region. We performed ileocecal resection, an ileostomy and a mucous fistula of the ascending colon. Histopathological examinations revealed pseudodiverticula at the perforation, where the mucosa was depressed through the muscularis propria. Hence, we diagnosed perforated ileal diverticulitis. Repeated diverticulitis triggered by chemotherapy might have resulted in perforation. Small bowel diverticula are rare, but diverticulitis can occur in patients receiving chemotherapy and with cases of unexplained fever and abdominal pain.

Neuroendocrine carcinoma associated with chronic ulcerative colitis: a case report and review of the literature.

Adenocarcinoma is a common histological type of ulcerative colitis-associated cancer (UCAC), whereas neuroendocrine carcinoma (NEC) is extremely rare. UCAC is generally diagnosed at an advanced stage, even with regular surveillance colonoscopy. A 41-year-old man with a 17-year history of UC began receiving surveillance colonoscopy at the age of 37 years; 2 years later, dysplasia was detected in the sigmoid colon, and he underwent colonoscopy every 3 to 6 months. Approximately 1.5 years thereafter, a flat adenocarcinoma lesion occurred in the rectum. Flat lesions with high-grade dysplasia were found in the sigmoid colon and surrounding area. The patient underwent laparoscopic total proctocolectomy and ileal pouch-anal anastomosis with ileostomy. Adenocarcinoma was diagnosed in the sigmoid colon and NEC in the rectum. One year postoperation, recurrence or metastasis was not evident. Regular surveillance colonoscopy is important in patients with long-term UC. A histological examination of UCAC might demonstrate NEC.

Metastasis of Ovarian Cancer to the Descending Colon.

Colonic metastasis from ovarian cancer is extremely rare, with only seven reported cases. A 77-year-old woman who had previously undergone surgery for ovarian cancer was admitted to a local hospital with anal bleeding. Histopathological analysis confirmed the presence of adenocarcinoma. Colonoscopy revealed a descending colon tumor. The patient was diagnosed with Union for International Cancer Control T3N0M0 descending colon cancer or colon metastasis of the ovarian cancer. Laparoscopic left colectomy was performed; intraoperative frozen section diagnosis confirmed metastasis from ovarian cancer, and the absence of invasion to the serosal surface suggested hematogenous metastasis. This is the first case of colonic metastasis from ovarian cancer that was diagnosed using an intraoperative frozen section and laparoscopically treated.

Three-dimensional visualization of the total mesorectal excision plane for dissection in rectal cancer surgery and its ability to predict surgical difficulty.

Total mesorectal excision (TME) for rectal cancer is often technically challenging. We aimed to develop a method for three-dimensional (3D) visualization of the TME dissection plane and to evaluate its ability to predict surgical difficulty. Sixty-six patients with lower rectal cancer who underwent robot-assisted surgery were retrospectively analyzed. A 3D TME dissection plane image for each case was reconstructed using Ziostation2. Subsequently, a novel index that reflects accessibility to the deep pelvis during TME, namely, the TME difficulty index, was defined and measured. Representative bony pelvimetry parameters and clinicopathological factors were also analyzed. The operative time for TME was used as an indicator of surgical difficulty. Univariate regression analysis revealed that sex, body mass index, mesorectal fat area, and TME difficulty index were associated with the operative time for TME, whereas bony pelvimetry parameters were not. Multivariate regression analysis found that TME difficulty index (ß = - 0.398, P = 0.0025) and mesorectal fat area (ß = 0.223, P = 0.045) had significant predictability for the operative time for TME. Compared with conventional bony pelvimetry parameters, the TME difficulty index and mesorectal fat area might be more useful in predicting the difficulty of rectal cancer surgery.

Preoperative Simulation of Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis Using a 3-Dimensional Printed Model.

BACKGROUND: During restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis-associated colorectal cancer or dysplasia, ileal pouch-anal handsewn anastomosis (IAA) is preferred to avoid the risk of cancer development in the remaining rectal mucosa. However, there is a risk of the ileal pouch not reaching the anus with this procedure. Here, we created deformable 3-dimensional (3D) models for simulation. METHOD: Six patients who underwent IAA without vessel ligation and 5 patients who underwent ileal pouch-anal canal double-stapled anastomosis (IACA) because the ileal pouch did not reach the anus were studied. A 3D printer was used to create deformable 3D models from the data obtained from computed tomography scans. The positional relationship among the mesenteric arteries, pubis, and coccyx were evaluated. RESULT: The distance between the superior mesenteric artery root and the tip of the ileal artery was longer in the IAA group than that in the IACA group (IAA vs IACA: 26.2 ±â€…2.1 cm vs 20.9 ±â€…1.6cm). The distance from the tip of the ileal artery to the coccyx (IAA vs IACA: 6.7 ±â€…1.7 cm vs 12.1 ±â€…2.1 cm) and the distance from the tip of the ileal artery to the lower edge of the pubis (IAA vs IACA; 8.1 ±â€…1.3 cm vs 12.7 ±â€…2.4 cm) were longer in the IACA group than those in the IAA group. CONCLUSIONS: We established a method for creating 3D deformable models of patients with ileal pouch-anal anastomosis. These 3D models may be useful for preoperative simulation.

We established the method for creating deformable 3-dimensional models of the patients who underwent restorative proctocolectomy with ileal pouch­anal anastomosis, and the distance from the tip of the ileal artery to the coccyx was shorter in ileal pouch­anal handsewn anastomosis group.

Sarcopenia is Associated With Oncological Prognosis and the Incidence of Secondary Cancer in Patients With Middle/Lower Rectal Cancer.

OBJECTIVE: This study evaluated the clinical implications of sarcopenia for patients with rectal cancer according to cancer progression. SUMMARY BACKGROUND DATA: The negative impact of body composition on long-term outcome has been demonstrated for various malignancies. METHODS: We retrospectively reviewed 708 patients with rectal cancer who underwent curative resection at our institution between 2003 and 2020. Factors contributing to long-term outcomes and the incidence of secondary cancer (ISC) were analyzed. Psoas muscle mass index (PMI) was assessed using preoperative computed tomography. Sarcopenia was defined using the PMI cut-off values for Asian adults (6.36 cm2/m2 for males and 3.92 cm2/m2 for females). RESULTS: Sarcopenia was identified in 306 patients (43.2%). Sarcopenia was associated with advanced age, low body mass index, smoking history, and advanced T-stage. Multivariate analysis showed sarcopenia was an independent poor prognostic factor for OS (HR 1.71; P = .0102) and cancer-specific survival (HR 1.64; P = .0490). Patients with sarcopenia had significantly higher mortality due to cancer-related death in stages III and IV, whereas non-rectal cancer-related death, including secondary cancer, was markedly increased in stage 0-II sarcopenic rectal patients. Five-year cumulative ISC in patients with and without sarcopenia was 11.8% and 5.9%, respectively. Multivariate analysis revealed that sarcopenia was an independent predictive factor for ISC (HR 2.05; P = .0063). CONCLUSIONS: Sarcopenia helps predict survival outcomes and cause of death according to cancer stage for patients with middle/lower rectal cancer who underwent radical surgery. Furthermore, sarcopenia increased the development of secondary cancer in those patients.

Low Expression of SNAI1 in Lymph Node Metastasis Indicates Delayed Recurrence of Colonic Cancer.

BACKGROUND/AIM: Even though epithelial-mesenchymal transition markers in primary tumors are identified as a helpful indicator of cancer metastasis and prognosis, their expression in lymph node metastases (LNMs) remains poorly described. We aimed to investigate the difference between snail family transcriptional repressor 1 (SNAI1) and E-cadherin expression in primary tumors and LNMs, and how it affects prognosis. PATIENTS AND METHODS: From 2010 to 2014, 127 patients who underwent radical surgery for stage III colonic adenocarcinoma without preoperative treatment were retrospectively reviewed for SNAI1 and E-cadherin expression in primary tumors and LNMs. RESULTS: High SNAI1 expression was found in 76% and 70% of primary tumors and LNMs, respectively, and low E-cadherin expression was found in 73% and 84%, respectively. High expression of SNAI1 in LNMs significantly correlated with poor overall and relapse-free survival rates. Even though the rate of liver metastasis at 5 years was similar for the groups with high and low SNAI1 expression in LNMs, the incidence in the group with low SNAI1 expression in the second year was higher than that in the first year (33% vs. 17%), whilst in the group with high SNAI1 expression, the incidence in the first year was higher than in the second year (71% vs. 29%). The rate of recurrence of lung metastasis was significantly lower when SNAI1 expression in LNMs was low (p=0.031). CONCLUSION: Low expression of SNAI1 in LNMs of colonic adenocarcinoma may indicate delayed recurrence in the liver and lung.

Paraganglioma of the urinary bladder initially diagnosed as gastrointestinal stromal tumor requiring combined resection of the rectum: a case report.

BACKGROUND: Paraganglioma of the urinary bladder (Pub) is rare and presents with clinical symptoms caused by catecholamine production and release. The typical symptoms of Pub are hypertension, macroscopic hematuria, and a hypertensive crisis during micturition. The average size of detected Pubs is approximately 3 cm. Herein, we report a case of a large Pub in which the symptoms were masked by oral medication, precise preoperative diagnosis was difficult, and intraoperative confirmation of tumoral adhesion to the rectum resulted in hypertensive attacks during surgery. CASE PRESENTATION: A 64-year-old Japanese male with a history of hypertension and arrhythmia controlled with oral medication presented with a large tumor in the pelvic region, detected on examination for weight loss, with no clinical symptoms. Computed tomography and magnetic resonance imaging revealed a tumor measuring 77 mm in diameter in the posterior wall of the urinary bladder. The border with the rectum was unclear, and the tumor showed heterogeneous enhancement in the solid part with an enhancing hypodense lesion. Cystoscopy revealed compression of the bladder trigone by external masses; however, no tumor was visible in the lumen. Endoscopic ultrasonography-guided fine-needle aspiration revealed CD34-positive spindle-shaped cells in the fibrous tissue, suggestive of a mesenchymal neoplasm. The tumor was suspected to be a gastrointestinal stromal tumor, and surgery was performed. After laparotomy, we suspected that the tumor had invaded the rectum, and total cystectomy and anterior resection of the rectum were performed. Histologically, the tumor cells had granular or clear amphophilic cytoplasm with an oval nucleus and nests of cells delimited by connective tissue and vascular septations. Immunohistochemically, the tumor was positive for chromogranin A, CD56, and synaptophysin, and a diagnosis of paraganglioma of the urinary bladder was confirmed. There was no tumor recurrence at the 7-month follow-up. CONCLUSION: This case highlights the importance of careful examination of pelvic tumors, including endocrine testing, for detecting paraganglioma of the urinary bladder in patients with a history of hypertension or arrhythmia.

A Polymorphism in Interleukin-1ß Gene Is Associated with the Development of Pouchitis in Japanese Patients with Ulcerative Colitis.

BACKGROUND: Major complications in patients with ulcerative colitis (UC) include UC-associated cancer (UCAC) and postoperative pouchitis. We aimed to identify SNPs associated with UCAC/high-grade dysplasia (HGD) and pouchitis. METHODS: Patients with UC who underwent ileal pouch-anal anastomosis (IPAA) with >2 years of follow-up after functioning pouches were included. Pouchoscopies were performed at least once to diagnose pouchitis according to the modified pouchitis disease activity index. SNP genotyping was performed for 8 SNPs reportedly associated with UCAC and pouchitis, namely: ELF1 (rs7329174), FCGR2A, (rs1801274), interleukin-1ß (IL-1B; rs1143627), ITLN1 (rs2274910), MHC (rs7765379), TNFα (rs1799964), TNFSF15 (rs3810936), and UHMK1 (rs768910), using TaqMan genotyping technologies. We investigated the association of these SNPs with UCAC/HGD and pouchitis. Patients' background data were retrospectively collected, including the presence of preoperative extraintestinal manifestation (EIM). RESULTS: A total of 91 Japanese patients with UC were included. None of the 8 SNPs were associated with UCAC/HGD in our cohort. Multivariable analyses proved that the presence of preoperative EIM (hazard ratio [HR] 3.313, 95% CI 1.325-8.289) and IL-1B (rs1143627) TT genotype (HR 2.425, 95% CI 1.049-5.61) were independent predictive factors for the development of overall pouchitis. The presence of preoperative EIM (HR 3.977, 95% CI 1.292-12.24) and IL-1B (rs1143627 TT genotype; HR 3.382, 95% CI 1.101-10.39) were also independent predictive factors for the development of chronic pouchitis. CONCLUSIONS: The IL-1B (rs1143627) TT genotype and preoperative EIM were statistically significant predictors of pouchitis development after IPAA in patients with UC.

Rate of Reoperation Decreased Significantly After Year 2002 in Patients With Crohn's Disease.

BACKGROUND & AIMS: Patients with Crohn's disease (CD) can require multiple intestinal surgeries. We examined time trends and risk factors for reoperation in patients with CD who underwent intestinal surgery, focusing on the effects of postoperative medical treatments. METHODS: We performed a retrospective analysis of 1871 patients with CD who underwent initial intestinal resection at 10 tertiary care institutions in Japan, with an initial surgical date after May 1982. We collected data on the background characteristics of all patients, including Montreal Classification, smoking status, and medical therapy after surgery (tumor necrosis factor antagonists [anti-TNF] agents or immunomodulators). The primary outcome was requirement for first reoperation. Rate of reoperation was estimated using the Kaplan-Meier method, and risk factors for reoperation were identified using the Cox regression model. RESULTS: The overall cumulative 5- and 10-year reoperation rates were 23.4% and 48.0%, respectively. Multivariable analysis showed that patients who underwent the initial surgery after May 2002 had a significantly lower rate of reoperation than patients who underwent surgery before April 2002 (hazard ratio [HR], 0.72; 95% CI, 0.61-0.86). Preoperative smoking (HR, 1.40; 95% CI, 1.18-1.68), perianal disease (HR, 1.50; 95% CI, 1.27-1.77), and ileocolic type of CD (HR, 1.42; 95% CI, 1.20-1.69) were significant risk factors for reoperation. Postoperative use of immunomodulators (HR, 0.60; 95% CI, 0.44-0.81) and anti-TNF therapy (HR, 0.71; 95% CI, 0.57-0.88) significantly reduced the risk. Anti-TNF was effective in the bionaive subgroup. CONCLUSIONS: The rate of reoperation in patients with CD significantly decreased after May 2002. Postoperative use of anti-TNF agents might reduce the reoperation rate for bionaive patients with CD.

Loss of RUNX3 Immunoreactivity in Non-Neoplastic Rectal Mucosa May Predict the Occurrence of Ulcerative Colitis-Associated Colorectal Cancer.

BACKGROUND/AIMS: Runt-related transcription factor (RUNX) 3 is a tumor suppressor whose expression is reduced in non-neoplastic rectal mucosa of patients with ulcerative colitis (UC) with coexisting colitis-associated cancer (CAC). We aimed to evaluate RUNX3 utility as a predictive marker for CAC using immunohistochemistry (IHC) for non-neoplastic UC mucosa. METHODS: We retrospectively compared the RUNX3 expression detected by IHC between non-neoplastic rectal biopsy specimens from 20 cases with invasive cancer (CAC group) and 20 cases selected from 138 patients without CAC (non-CAC group) that were treated during the same period (2006-2017) and were matched for sex, duration, extension, and age. We validated the results using tissue microarrays (TMA) of 44 operated cases with CAC. The RUNX3 expression level was determined by calculating the percentage of RUNX3-positive-cells. RESULTS: The RUNX3 expression was lower in the CAC than that in the non-CAC group (35.6 vs. 70.7%, p = 0.03). For a cutoff value of 58%, the sensitivity and specificity for predicting CAC were 75.0 and 70.0% respectively. The immunostaining results for the TMA showed the same trend; 74% of cases with CAC were negative for the RUNX3 expression. CONCLUSION: RUNX3 immunostaining of non-neoplastic mucosa is useful for identifying UC patients at a high risk of developing CAC.

Laparoscopic surgery in rectal cancer patients taking anti-thrombotic therapy.

Background: Several previous studies have shown that laparoscopic resection of rectal cancer is a feasible option. However, its safety and efficacy in patients receiving long-term anti-thrombotic therapy (AT) remain unclear.Material and methods: We retrospectively reviewed 364 patients who underwent elective resection for rectal cancer via a laparoscopic approach between 2007 and 2018 in our institute. Patients were classified according to the long-term use of AT. AT was interrupted perioperatively with or without heparin bridging therapy in all anti-thrombotic users. Clinicopathological factors and surgical outcomes were analyzed between patient groups.Results: Thirty-two patients (9%) receiving AT were older and had lower albumin and hemoglobin levels than those not receiving AT (the non-AT group), and were predominantly male. Estimated blood loss and operative time in the AT group (median: 50 mL and 294 min) did not differ from those in the non-AT group (median: 20 mL and 295 min). There were no intergroup differences in the frequencies of other postoperative complications and oncological outcomes.Conclusions: Our results at the very least can support that laparoscopic surgery for rectal cancer is a safe and feasible option for patients taking long-term AT discontinued perioperatively.