Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy.

BACKGROUND: The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. OBJECTIVES: We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). METHODS: We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. CONCLUSIONS: The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.

Radiological Cutoff Values for Diagnosis of Lymph Node Metastasis in Colorectal Cancer With Multilevel Analysis.

Background/Aim: A cutoff value for lymph node diameter in colorectal cancer lymph node metastases has not been established. This prospective study aimed to investigate the direct association between swollen lymph nodes identified on preoperative computed tomography (CT) and pathological findings and proposed a cutoff value. Patients and Methods: We enrolled patients scheduled to undergo curative surgery with lymph node dissection for colorectal adenocarcinoma who underwent preoperative contrast-enhanced CT and had swollen lymph nodes ≥7 mm in diameter. Two gastrointestinal surgeons intraoperatively identified the target lymph nodes to assess the association between lymph node diameter and pathological findings. The diagnostic performance for lymph node metastasis was determined using multi-level logistic modelling. Results: A total of 109 patients were enrolled, and 225 swollen lymph nodes were pathologically evaluated. Using a cutoff value of ≥9 mm for the short diameter, the positive and negative predictive values, sensitivity, and specificity were 100.0% (99.6%-100.0%), 99.9% (99.1%-100.0%), 62.0% (45.6%-76.0%), and 84.9% (67.0%-94.0%), respectively. Conclusion: The cutoff value for improving the positive predictive value for the preoperative lymph node metastasis diagnosis in colorectal cancer patients should be at least 9 mm in diameter.

The pattern-based interpretation of p53 immunohistochemical expression as a surrogate marker for TP53 mutations in colorectal cancer.

Mutations in the TP53 gene, most commonly observed in colorectal cancer (CRC), play an essential role in colorectal carcinogenesis. Although p53 immunohistochemical (IHC) expression patterns have been argued to serve as an excellent surrogate marker for TP53 mutations, its performance has not been confirmed in CRC. We aimed to determine whether p53 IHC expression patterns accurately predict TP53 mutation status as examined by next-generation sequencing (NGS). We performed p53 IHC and sequencing of TP53 by NGS in 92 CRC cases with a microsatellite stable phenotype to investigate the correlation between TP53 mutation status and p53 IHC expression. The concordance between p53 IHC and TP53 mutation was 84/92 (91.3%) overall. However, 6 mutant cases were found in 39 cases with a wild-type IHC pattern. Additionally, there were two discordant cases in which an abnormal p53 IHC pattern (overexpression or cytoplasmic pattern) was found, while NGS detected wild-type p53. Therefore, the optimized p53 IHC performs well and serves as a surrogate test for TP53 mutation in CRC cases. Furthermore, it demonstrates excellent reproducibility between two independent experienced pathologists and may have novel clinical utility for molecular classification algorithms in CRC. We suggest that the four-tier classification of p53 IHC patterns is helpful to evaluate molecular colorectal carcinogenesis.

Prognostic impact and survival outcomes of colon perforation in patients with metastatic colorectal cancer: a multicenter retrospective cohort study.

BACKGROUND: Colon perforation caused by colorectal cancer (CRC) is a fatal condition requiring emergency intervention. For patients with metastatic lesions, surgeons face difficult decisions regarding whether to resect the primary and metastatic lesions. Moreover, there is currently no established treatment strategy for these patients. This study aimed to investigate the clinical practice and long-term outcomes of patients with metastatic CRC diagnosed with the onset of colon perforation. METHODS: We performed a population-based multicenter cohort study. Consecutive patients diagnosed with stage IV CRC between 2008 and 2015 at all designated cancer hospitals in Fukushima Prefecture, Japan, were enrolled in this study. We evaluated the impact of colon perforation on the survival outcomes of patients with metastatic CRC. The main outcome was the adjusted hazard ratio (aHR) of perforation for overall survival (OS). Survival time and HRs were estimated using Kaplan‒Meier and Cox proportional regression analyses. RESULTS: A total of 1258 patients were enrolled (perforation: n = 46; non-perforation: n = 1212). All but one of the patients with perforation underwent primary resection or colostomy and 25 cases were able to receive chemotherapy. The median OS for the perforation and non-perforation groups was 19.0 and 20.0 months, respectively (p = 0.96). Moreover, perforation was not an independent prognostic factor (aHR: 0.99; 95% confidence interval: 0.61-1.28). CONCLUSIONS: In metastatic CRC, perforation is not necessarily a poor prognostic factor. Patients with perforation who undergo primary tumor resection or colostomy and prompt initiation of systemic chemotherapy might be expected to have a survival time similar to that of patients with non-perforated colon.

Clinical Indicators to Determine the Timing of Surgery for Adhesive Small Bowel Obstruction.

BACKGROUND: Decompression of the intestine with a long tube or nasogastric tube is the first-choice treatment for adhesive small bowel obstruction (ASBO). Scheduling surgery while weighing the risks of surgery against conservative care is a crucial factor in clinical decision-making. Whenever feasible, unnecessary surgeries should be avoided, and it is essential to provide clinical markers for this. This study aimed to obtain evidence regarding the optimal timing of ASBO and when conservative treatment options are not successful. METHODS: The data of patients diagnosed with ASBO and receiving long tube insertion for more than 7 days were reviewed. We investigated transit ileal drainage volume and recurrence. The primary outcomes were the change in the drainage volume from the long tube over time and the percentage of patients who required surgery. We evaluated some cutoff values to determine the indication for surgery based on the insertion duration and volume of long tube drainage. RESULTS: Ninety-nine patients were enrolled in this study. Fifty-one patients showed improvement with conservative treatment, whereas 48 ultimately required surgery. When a daily drainage volume of ≥500 mL was considered an indication for surgery, 13-37 cases (25%-72%) would be judged unnecessary within 6 days of long tube insertion, while 5 cases (9.8%) would be judged unnecessary on day 7. DISCUSSION: Unnecessary surgical interventions for ASBO might be avoided by assessing the drainage volume on day 7 after inserting a long tube.

Postoperative results and complications of fecal diversion for anorectal Crohn's disease.

PURPOSE: Fecal diversion is a less-invasive technique that can alleviate symptoms in patients with refractory anorectal Crohn's disease. However, complications, including recurrence of residual anorectal Crohn's disease, may develop. We aimed to evaluate the postoperative results and complications associated with fecal diversion in patients with refractory anorectal Crohn's disease. METHODS: We enrolled 1218 Crohn's disease patients who underwent laparotomy at our institute. We retrospectively analyzed the clinical features of 174 patients who underwent fecal diversion for refractory anorectal Crohn's disease, complications of the diverted colorectum, and the incidence and risk factors for proctectomy after fecal diversion. RESULTS: After fecal diversion, 74% of patients showed improved symptoms. However, bowel continuity restoration was successful in four patients (2.2%), and anorectal Crohn's disease recurred in all patients. Seventeen patients developed cancer with a poor prognosis. The rate of conversion to proctectomy after fecal diversion was 41.3%, and the risk factors included rectal involvement (p = 0.02), loop-type stoma (p < 0.01), and the absence of treatment with biologics after fecal diversion (p = 0.03). CONCLUSION: Fecal diversion for refractory anorectal Crohn's disease can improve clinical symptoms. Patients with rectal involvement or loop-type stoma have a greater risk of requiring proctectomy following fecal diversion. The administration of biologic may decrease the rate of proctectomy.

Relationship between physical activity and bone mineral density loss after gastrectomy in gastric cancer patients.

PURPOSE: The prevention of osteoporosis is a particularly relevant issue for gastric cancer survivors. We investigated the relationship between postoperative physical activity and the change of bone mineral density (BMD) in patients with gastric cancer. METHODS: Patients who underwent radical gastrectomy for gastric cancer were enrolled in this single-center prospective cohort study. Physical activity was evaluated using the International Physical Activity Questionnaire Short Form at postoperative month (POM) 6 and patients were classified into high, middle, and low physical activity groups accordingly. The primary outcome was the change in BMD from baseline at POM 12, which was expressed as a percentage of the young adult mean (YAM). The YAM of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. RESULTS: One hundred ten patients were enrolled in this study. The physical activity level at POM 6 was classified as high (n = 50; 45%), middle (n = 25; 23%), and low (n = 35; 32%). The mean decrease of YAM% was 5.1% in the lumbar spine and 4.2% in the femoral neck at POM 12. A multivariable-adjusted logistic regression model revealed that low physical activity at POM 6 was a significant risk factor for BMD loss at POM 12 (odds ratio, 3.76; 95% confidence interval, 1.48-9.55; p = 0.005). CONCLUSION: Low physical activity after gastrectomy is an independent risk factor for decreased BMD at POM 12. The introduction of exercise may prevent osteoporosis after the surgical treatment of gastric cancer.

[A case of a patient with Crohn's disease who had vaginal delivery after abdominoperineal resection for severe anorectal complications].

We report the case of a young female patient with Crohn's disease case who had vaginal delivery after abdominoperineal resection for severe perianal disease. The patient had Crohn's disease with anorectal complications for 13 years and underwent abdominoperineal resection for anorectal stenosis, complex anal fistula, and rectovaginal fistula in her early twenties. Seven years later, she got pregnant and gave birth to a healthy boy by vaginal delivery. No recurrence of Crohn's disease was observed during the perinatal period. There is no curative treatment for severe anorectal complications, which may be necessary for young patients to undergo abdominoperineal resection. Further studies are needed to determine the effects of Crohn's disease with anorectal complications on pregnancy and childbirth in affected patients.

[Pregnancy and delivery in patients with Crohn's disease who had a history of abdominal surgery].

OBJECTIVE: A few studies have focused on pregnancy and childbirth in patients with Crohn's disease (CD) who had a history of abdominal surgery. The objective of this study is to analyze the problems of pregnant patients with CD with a history of abdominal surgery. METHODS: The rates of pregnancy-related complications and adverse birth outcomes were retrospectively analyzed in 29 patients with CD (45 pregnancies) with previous intestinal surgery. RESULTS: In this study, the following outcomes were observed:normal births occurred in 55.6% of the pregnancies, preterm births in 13.3%, and spontaneous abortions in 20.0%. The vaginal birth and cesarean section rates were 45.7% and 40.0%, respectively. The rate of low-birth weight infants was 14.3%. CONCLUSION: Overall, patients with CD with previous abdominal surgery can conceive and give birth. However, care needs to be taken to avoid preterm birth, spontaneous abortion, low birth weight, and cesarean delivery.

[Preoperative diagnosis of small intestinal cancer associated with Crohn's disease: a case report].

The patient was a 46-year-old woman with a history of Crohn's disease for several years. At 45 years of age, a colonoscopy was performed, and a protruding lesion in the terminal ileum was detected. Pathological analysis of a biopsy specimen noted high suspicion for a well differentiated adenocarcinoma. The patient underwent ileocecal resection, and histological examination of the specimen revealed that infiltration of the well differentiated adenocarcinoma was limited to the mucosa. To the best of our knowledge, this is the first known case of early small intestinal cancer associated with Crohn's disease in Japan. Both endoscopy and a biopsy of any protruding lesions may be useful for making a preoperative diagnosis of small intestinal cancer associated with Crohn's disease.

Subtotal colectomy for refractory ulcerative colitis with COVID-19 infection; a first case report in Japan.

We report a 60-year-old male who was transferred to our hospital for the operation because of refractory ulcerative colitis (UC). He was diagnosed to be infected with COVID-19 for SARS-CoV-2 PCR test positive at the time of transfer. We determined emergency operation because his general condition was poor such as malnutrition and ADL decline due to exacerbation of UC and air embolization by central venous catheter removal. He underwent subtotal colectomy with a sigmoid mucous fistula and ileostomy. He was well postoperatively. This is a first case report in Japan who underwent an operation for UC with COVID-19 infection.

Clinicopathological and prognostic evaluations of anorectal cancer after fecal diversion for patients with Crohn's disease.

PURPOSE: Colorectum diversion with a proximal stoma is often the preferred surgical approach in patients with Crohn's disease-related anorectal lesions or refractory colitis. To date, few studies have assessed the incidence and prognosis of cancer in the diverted anorectal segments. This study aimed to evaluate the clinical characteristics and prognosis of anorectal cancer associated with Crohn's disease following fecal diversion. METHODS: This was a retrospective study based on medical records of patients diagnosed with Crohn's disease between 1999 and 2020. It was conducted at Yokohama Municipal Citizen's Hospital. Patients diagnosed with anorectal cancer following fecal diversion were identified, and their prognosis was the primary outcome measure. RESULTS: Among 1615 patients, 232 patients (14%) underwent colorectum diversion. Of those 232 patients, 11 were diagnosed with anorectal cancer following fecal diversion, ten were diagnosed with advanced cancer, 10 underwent abdominoperineal resection, and eight died. 1 could not undergo resection due to multiple lung metastasis and died. The overall five-year survival rate in patients diagnosed with anorectal cancer following fecal diversion was 20%. CONCLUSION: Crohn's disease-associated anorectal cancer following fecal diversion was challenging to diagnose early, and patients had a poor prognosis even after curative resection. Early abdominoperineal resection may be considered for patients with Crohn's disease who cannot benefit from cancer screening and surveillance due to difficulty accessing the anorectal stricture via endoscopy.

[A case of ulcerative colitis complicated by internal fistula between the transverse colon and stomach].

A case of ulcerative colitis (UC) with an internal fistula was reported;the patient, a 42-year-old male, was admitted to the hospital with a diagnosis of refractory UC. The preoperative examination revealed an internal fistula between the transverse colon and the stomach. UC was diagnosed preoperatively with an internal fistula, but the possibility of Crohn's disease could not be ruled out at that time. The patient underwent subtotal colectomy with end ileostomy, sigmoid colon mucous fistula, and partial gastrectomy. UC was diagnosed histopathologically, and an ileal pouch-anal anastomosis was performed. An internal fistula can complicate UC;a split surgery is recommended with the possibility of Crohn's disease in the patient.

[Seven Cases of Metastatic Colorectal Cancer Treated with Dose-Reduced and Duration-Reduced Regorafenib Treatment].

Regorafenib is widely used for patients with metastatic colorectal cancer, following disease progression with standard therapies.However, regorafenib has severe toxicities; therefore, careful monitoring and treatment are necessary.Several studies have investigated the efficacy of initial dose reductions.We started regorafenib doses from 80 mg, with a duration of 1 week on and 1 week off, after which we gradually increased the dosage and duration.From September 2015 to March 2017, we treated 7 consecutive patients who received regorafenib following standard chemotherapy for metastatic colorectal cancer.The average age was 73 years and average BMI was 23.3.The average total dose was 15,960(2,240-28,000)mg, and the average treatment duration was 243(50-379)days.The mean survival from the start of regorafenib was 399(median 407, 262-622)days.Adverse events of Grade 3 or higher were observed in 1 patient(14%).