Colorectal cancer and advanced adenoma characteristics according to causative mismatch repair gene variant in Japanese colorectal surveillance for Lynch syndrome.

BACKGROUND: The optimal interval of colonoscopy (CS) surveillance in cases with Lynch syndrome (LS), and stratification according to the causative mismatch repair gene mutation, has received much attention. To verify a feasible and effective CS surveillance strategy, we investigated the colorectal cancer (CRC) incidence at different intervals and the characteristics of precancerous colorectal lesions of LS cases. METHODS: This retrospective multicenter study was conducted in Japan. CRCs and advanced adenomas (AAs) in 316 LS cases with germline pathogenic variants (path_) were analyzed according to the data of 1,756 registered CS. RESULTS: The mean time interval for advanced CRCs (ACs) detected via CS surveillance was 28.7 months (95% confidence interval: 13.8-43.5). The rate of AC detection within (2.1%) and beyond 2 years (8.7%) differed significantly (p = 0.0003). AAs accounted for 43%, 46%, and 41% of lesions < 10 mm in size in the MLH1-, MSH2-, and MSH6-groups, respectively. The lifetime incidence of metachronous CRCs requiring intestinal resection for path_MLH1, path_MSH2, and path_MSH6 cases was 34%, 23%, and 14% in these cases, respectively. The cumulative CRC incidence showed a trend towards a 10-year delay for path_MSH6 cases as compared with that for path_MLH1 and path_MSH2 cases. CONCLUSIONS: In cases with path_MLH1, path_MSH2, and path_MSH6, maintaining an appropriate CS surveillance interval of within 2 years is advisable to detect of the colorectal lesion amenable to endoscopic treatment. path_MSH6 cases could be stratified with path_MLH1 and MSH2 cases in terms of risk of metachronous CRC and age of onset.

Marital status after colorectal surgery in familial adenomatous polyposis: a nationwide multicenter study in Japan.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) experience psychological and social challenges concerning future events such as marriage and childbirth alongside the medical risks of colorectal cancer (CRC) and FAP-related disease. We retrospectively investigated the rate of marriage and childbirth postoperatively in Japanese patients with FAP. METHODS: We included 161 patients who had colorectal surgery and reported marital status from a national survey of 35 Japanese institutions. Participants were classified according to marital status: married before colectomy (80 patients), married after colectomy (13 patients), and unmarried (68 patients). RESULTS: The marriage rate for all 161 patients (57.8%, standardized ratio 0.95, 95% confidence interval [CI] 0.76-1.14) was comparable to that in the general Japanese population (57.1%). The marriage rate among the 81 patients who were unmarried before colectomy was low (16.0%); however, the standardized marital ratio (0.75, 95% CI 0.34-1.15) was not significantly lower than that of the general population. In multivariable logistic regression, younger age (born after 1980, odds ratio [OR] 0.12, p < 0.001) and genetic testing (OR 4.06, p = 0.001) were associated with postoperative marriage. Seventy-one percent of patients with FAP who married after colectomy became pregnant and achieved delivery. CONCLUSIONS: The marriage rate of patients with FAP was comparable to that of the general population whereas the rate after colectomy was low among patients with FAP. However, in patients with FAP, colorectal surgery itself may not lead to negative consequences in terms of fecundity.

Laparoscopic transabdominal approach for resection of presacral epidermoid cyst in an obese man: a case report.

BACKGROUND: Complete resection of presacral epidermoid cysts is recommended due to the potential for infection or malignancy. Transsacral and transabdominal approaches have been used to treat presacral tumors. However, there are no standard surgical approaches to resection. We present the case of a presacral epidermoid cyst in an obese male patient who underwent laparoscopic transabdominal resection. CASE PRESENTATION: A 44-year-old man was referred to our hospital for treatment of a cystic tumor on the pelvic floor. Contrast-enhanced computed tomography revealed a 45 × 40-mm tumor on the left ventral side of the rectum, right side of the ischial spine, dorsal side of the seminal vesicles, and in front of the 5th sacrum. Enhanced magnetic resonance imaging revealed a multilocular cystic tumor with high and low signal intensities on T2-weighted images. The tumor was diagnosed as an epidermoid cyst. We considered the transsacral or laparoscopic approach and decided to perform a laparoscopic-assisted transabdominal resection since the tumor was in front of away from the sacrum, and a transsacral approach would result in a larger scar due to poor visibility from the thickness of the buttocks. The entire tumor was safely resected under laparoscopic guidance, because the laparoscopic transabdominal approach can provide a good and magnified field of view even in a narrow pelvic cavity with small skin incisions, allowing safe resection of the pelvic organs, vessels, and nerves while observing the tumor contour. CONCLUSIONS: The laparoscopic transabdominal approach is an effective method for treating presacral tumors in obese patients.

Aortoesophageal fistula due to esophageal cancer: a case report of successful management.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare but potentially life-threatening condition. The best treatment for the AEF due to esophageal carcinoma is still unresolved. Here, we report a rare case of AEF caused by esophageal cancer, that was successfully treated with emergency thoracic endovascular aortic repair (TEVAR), followed by esophagectomy and gastric tube reconstruction. CASE PRESENTATION: A 64-year-old man presented with loss of consciousness and hypotension during chemoradiotherapy for advanced esophageal cancer. Enhanced computed tomography showed extravasation from the descending aorta into the esophagus at the tumor site. We performed emergency TEVAR for the AEF, which stabilized the hemodynamics. We then performed thoracoscopic subtotal esophagectomy on day 4 after TEVAR to prevent graft infection, followed by gastric tube reconstruction on day 30 after TEVAR. At 9 months after the onset of AEF, the patient continues to receive outpatient chemotherapy and leads a normal daily life. CONCLUSION: TEVAR is a useful hemostatic procedure for AEF. If the patient is in good condition and can continue treatment for esophageal cancer, esophagectomy and reconstruction after TEVAR should be performed to prevent graft infection and maintain quality of life.

Risk of metachronous colorectal cancer after surgical resection of index rectal cancer in Lynch syndrome: a multicenter retrospective study in Japan.

PURPOSE: This study evaluated the risk of metachronous colorectal cancer (CRC) after resection of index (first) rectal cancer in patients with Lynch syndrome (LS). METHODS: Clinicopathological data of patients with genetically proven LS were retrospectively analyzed in this multicenter Japanese study. The cumulative incidence of metachronous CRC and the overall survival were compared between patients with index rectal cancer (rectal group) and those with index colon cancer (colon group). RESULTS: The median age at index CRC surgery was lower in the rectal group than in the colon group (37 vs. 46 years old, P = 0.01). The cumulative 5-, 10-, and 20-year incidences of metachronous CRC were 3.5%, 13.9%, and 21.1%, respectively, in the rectal cancer group and 14.9%, 22.0%, and 57.9%, respectively, in the colon cancer group (P = 0.02). The overall survival curves were not significantly different between two groups (P = 0.23). CONCLUSION: This is the first report from an East Asian country to report the risk of metachronous CRC after resection of index rectal cancer in patients with LS. Despite this study having several limitations, we cannot recommend extended resection, such as total proctocolectomy, for index rectal cancer as a standard surgical treatment in patients with LS.

Risk of metachronous colorectal cancer after colectomy for first colon cancer in Lynch syndrome: multicenter retrospective study in Japan.

BACKGROUND: We evaluated the risk of metachronous colorectal cancer (mCRC) and explored the optimal extent of colectomy in patients with Lynch syndrome (LS) and first colon cancer (fCC) in Japan, where the extent of colectomy for colon cancer (CC) is shorter than that in Western countries. METHODS: The clinicopathologic and survival data of patients with LS who developed CC were collected from a nationwide database and analyzed retrospectively. The cumulative incidence of mCRC after actual segmental colectomy was compared with that of mCRC when more extensive colectomy was assumed. RESULTS: There were 142 eligible patients (65 female). The median age at fCC surgery was 46.5 (range: 14-80) years. The cumulative incidence of 5-, 10-, and 20-year mCRC rate was 13.4%, 20.8%, and 53.6%, respectively. The incidence was higher in the left-sided group (splenic flexure to rectosigmoid colon, n = 54) than in the right-sided group (cecum to transvers colon, n = 88) (66.3% vs. 45.3% in 20 years, P < 0.01). Assuming that all patients would have undergone hemicolectomy or total colectomy, the estimated mCRC risk was 41.5% and 9.4% (P < 0.01, vs. actual procedures), respectively. The 20-year overall survival rate of all the patients was 83.3% without difference by fCC sidedness (P = 0.38). CONCLUSIONS: To reduce the incidence of mCRC, patients with genetically diagnosed LS and fCC, preferentially located in the left-sided colon, may need to undergo more extended colectomy than that usually performed in Japan. However, such extended colectomy should be counterbalanced with favorable overall survival and actual risk of mCRC development.

Significance of Desmoplastic Histopathological Growth Pattern for Colorectal Liver Metastases Treated With Preoperative Chemotherapy.

BACKGROUND/AIM: The aim of this study was to evaluate hepatectomy cases that underwent preoperative chemotherapy to examine the relationship between the development of desmoplastic histopathological growth pattern (dHGP) and prognosis and recurrence and determine whether it is useful for evaluating preoperative chemotherapy. PATIENTS AND METHODS: A total of 133 cases with hepatic metastasis for colorectal cancer that underwent surgical resection. RESULTS: Of the 102 cases that underwent preoperative chemotherapy, 34 (33%) were determined to be dHGP positive, which was statistically significantly higher than the 2 of 31 cases (6.5%) that had not undergone preoperative chemotherapy. Regarding the 5-year recurrence-free survival, the dHGP group had a value of 50.3%, whereas the non-dHGP group had a value of 7.1%. For the 5-year overall survival, the dHGP group had a better prognosis than the non-dHGP group (57.6% vs. 37.1%, respectively), with a statistically significant difference. Univariate analysis of recurrence-free survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and the presence or absence of dHGP were prognostic factors, whereas multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. Univariate analysis of the overall survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and presence or absence of dHGP were prognostic factors. Multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. CONCLUSION: dHGP is useful as a new evaluation method for evaluating the efficacy of preoperative chemotherapy.

Development of an Algorithm to Predict Recurrences After Resection of Liver Metastases in Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. PATIENTS AND METHODS: Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. RESULTS: In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. CONCLUSION: Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.

Simplified and Optimized Immune Score for Colorectal Cancer Microenvironment.

BACKGROUND/AIM: Immunoscore (IS) is an important evaluation method for the tumor immune microenvironment (TIME); however, formal IS analysis requires designated reagents and a specific digital pathology software and image data analysis. This study aimed to investigate whether simplified IS (s-IS) can substitute formal IS upon modifying the location of the assessment of the numbers of immune cells and verify that the addition of T cell subset markers to s-IS can enhance the prognostic impact in patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 82 CRC cases were included in this study. Immunohistochemical analysis was performed using CD3/CD8/CD45RO/FOXP3 on tissue specimens; the expression levels were calculated in the center and perimeter of the tumors using digital pathology. The clinical prognostic significance of the expression of these markers was investigated by concordance index comparison according to their location of assessment and combinations. RESULTS: In the univariate analysis, the CD3, CD8, and FOXP3 levels were significant prognostic factors. Moreover, for each T cell subset marker, the assessment of each T cell subset marker at the tumor perimeter had a stronger prognostic power than that in the tumor center. The modified s-IS (s-IS plus FOXP3 evaluation) was an independent prognostic factor for recurrence-free survival and overall survival through multivariate analysis and demonstrated the best prognostic power compared to other T subset marker combinations. CONCLUSION: In CRC, TIME evaluation could be simplified by assessing CD3- and CD8-positive T cells in the perimeter of the tumor, and additional FOXP3 evaluation would empower the ability of s-IS evaluation in prognostic assessment.

A Case of Immediate Anastomotic Leakage After Low Anterior Resection for Rectal Cancer.

A man in his seventies was referred to our hospital for radical therapy for advanced rectal cancer with multiple liver metastases. A colonic stent had already been placed in his rectum at the previous hospital because of malignant colorectal obstruction, so our therapeutic strategy was to perform systematic chemotherapy after resection of the primary tumor. Laparoscopic low anterior resection with a covering stoma was performed under general anesthesia. At about one hour after the surgery, the patient had sudden abdominal pain with watery diarrhea, and a similar discharge from his drainage tube. We suspected peritonitis caused by bowel perforation and emergency surgery was performed. The operative findings showed that his peritonitis was caused by anastomotic leakage from the rectum. Radical lavage of the abdominal space and reconstruction of colostomy was performed. The patient gradually recovered and we were able to start systematic chemotherapy at one month after the surgery. Anastomotic leakage immediately after anterior resection caused by watery diarrhea is rare, and it may be concerned with several issues. The covering stoma is intended to stop anastomotic leakage but it cannot prevent all cases of leakage especially when obstruction is present. We recommend that preventive measures be taken against anastomotic leakage, including intraoperative leakage tests or anal decompression tube placement.

Current practice of colonoscopy surveillance in patients with lynch syndrome: A multicenter retrospective cohort study in Japan.

Objectives: Colonoscopy surveillance reduces the incidence of colorectal cancer through the detection and endoscopic removal of adenomas. Current guidelines recommend that patients with Lynch syndrome should have colonoscopy surveillance every 1-2 years starting at the age of 20-25. However, insufficient data are available to evaluate the quality and safety of colonoscopy surveillance for patients with Lynch syndrome nationwide in Japan. Methods: Patients with Lynch syndrome (n = 309) from 13 institutions who underwent one or more colonoscopy procedures were enrolled in this retrospective analysis. Colonoscopy completion rate, colonoscopy-related complication rate, proportion with an adequate colonoscopy interval, and adenoma detection rate were reviewed. Results: The colonoscopy completion rate was 98.8% and a history of previous colorectal cancer surgery was significantly associated with a higher completion rate. All complications were associated with endoscopic treatment and the rate of bleeding needing hemostasis and perforation needing surgical repair were both 0.16% after colonoscopy with polypectomy. The adenoma detection rate at the first colonoscopy was 25%. Although there was no difference in the completion and complication rates based on differences in the colonoscopy experience of the endoscopist, the detection rate of adenomas and intramucosal cancers was significantly higher with more experienced endoscopists. The proportion of patients developing cancer was significantly higher with a >24 months than a ≤24 months interval. Conclusion: High-volume experienced endoscopists and appropriate surveillance intervals may minimize the risk of developing colorectal cancers in patients with Lynch syndrome.

Current clinical practice for familial adenomatous polyposis in Japan: A nationwide multicenter study.

Introduction: In Japanese patients with familial adenomatous polyposis (FAP), colectomy tends to be postponed or avoided. Aim: This study aimed to clarify the current clinical practice from a Japanese multicenter cohort study database. Methods: We analyzed the records of 250 patients with non-dense FAP who did not require colorectal cancer removal. The clinical outcomes were compared between patients who received colectomy (n = 142) (Group A) and those who did not receive colectomy (n = 108) (Group B). Results: The colectomy rate based on the age at the final follow-up examination was 46%, 60%, 54%, 65%, at ≤29, 30-39, 40-49, and ≥ 50 years, respectively (P = .11). The development of colorectal cancer did not differ between Groups A and B (25% vs 22% P = .67); however, colorectal cancer was diagnosed at the Tis stage in 88% of the patients with colorectal cancer in Group B, and 34% of the patients with colorectal cancer in Group A (P < .01). Regarding survival, all patients in Group B were alive at the final follow-up examination. In contrast, six patients in Group A died, including three patients with desmoid tumors and one with colon cancer. Conclusion: Over one-third of patients with non-dense FAP (polyps ≤ 1000) in Japan did not receive colectomy at >30 years of age, and patients who managed without colectomy showed acceptable survival with the early diagnosis of colorectal cancer, and a very low incidence of desmoid tumor development, indicating that this approach represents a potential option for the management of selected non-dense FAP patients.

Mismatch repair proteins expression and tumor-infiltrating T-cells in colorectal cancer.

Microsatellite instability (MSI) and tumor mutational burden (TMB) are indicators of the tumor mutational load, which can lead to immune cell recruitment. By contrast, the number of tumor-infiltrating T cells (TITs) is indicative of the host immune response to tumor cells. The present study evaluated if the expression of mismatch repair (MMR) proteins can be used as a precise tool to assess immunogenicity in the tumor microenvironment. A total of 73 colorectal cancer cases were enrolled in the present study. MMR protein expression was assessed using four-antibodies immunohistochemistry (IHC) targeting MLH1, MSH2, MSH6 and PMS2. TIT was assessed through IHC by counting CD3+ and CD8+ cells in tumor. The enrolled cases were classified into four groups according to MMR and TIT status i) Mismatch repair-proficient (pMMR) and a high number of TITs (pMMR/TIT-H); ii) pMMR and a low number of TITs (pMMR/TIT-L); iii) mismatch repair-deficient (dMMR) and TIT-H (dMMR/TIT-H); and iv) dMMR/TIT-L]. The present study evaluated the clinicopathological characteristics of the four groups, in addition to the difference of TMB. TMB analysis was counted the number of the somatic mutations through multi-genes panel using next-generation sequencing. Clinicopathological characteristics, including age, sex, pathological depth of invasion and lymph node metastasis, were not found to be statistically different between dMMR/TIT-H and dMMR/TIT-L groups. Tumors among pMMR/TIT-H group were associated with poorly differentiation compared with those in pMMR/TIT-L group (P=0.025). The median TMB among the dMMR/TIT-H group was the highest in four groups but the median TMB was <10 muts/Mb in dMMR/TIT-L, pMMR/TIT-H and pMMR/TIT-L groups, respectively. However, one tumor in the pMMR/TIT-H group showed high TMB. The present findings suggest that assessing MMR status alone may not be sufficient to precisely evaluate the antitumor immune response in the tumor microenvironment.

Significance of Intraperitoneal-free KRT20 and CEACAM6 mRNA Expression for Peritoneal Recurrence of Gastric Cancer.

BACKGROUND/AIM: Peritoneal lavage cytology is widely used to predict peritoneal recurrence after surgery, but cases of peritoneal recurrence are often recognized in patients with peritoneal lavage cytology negativity (CY0) who underwent no residual tumour (R0) surgery. We used peritoneal lavage fluid before and after gastric cancer surgery to detect cytokeratin 20 (KRT20) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) mRNA by RT-PCR. MATERIALS AND METHODS: We collected peritoneal lavage fluid before and after surgery from 58 patients who underwent gastrectomy. RNA was extracted from these samples and RT-PCR was performed. RNA expression was defined as positive and negative in cases with values higher or lower than the median value. We investigated the relationship between mRNA expression and clinicopathological and surgical factors and prognosis. RESULTS: Tumour invasion to the sub-serosa (T3) or penetration of the serosa (T4a), lymph node metastasis, and more than 150 ml intraoperative bleeding were significantly correlated with KRT20 mRNA expression. Multivariate analysis of its relationship with peritoneal recurrence showed that the odds ratio of CEACAM6 mRNA for recurrence was high (odds ratio=24.753; 95%CI=0.883-694.06; p=0.0592). All cases with peritoneal recurrence were CEACAM6-positive at pre- or post-surgery. The prognosis of peritoneal recurrence for both KRT20- and CEACAM6-positive cases was significantly poorer than that of other cases. The recurrence-free survival of the CEACAM6-positive group was significantly poorer than that of the CEACAM6-negative group. CONCLUSION: Measurement of CEACAM6 mRNA in peritoneal lavage fluid at pre- and post-surgery may be useful as a predictor of peritoneal recurrence.

Hematogenous Dissemination of Tumor Cells in Hepatocellular Carcinoma: Comparing Anterior and Non-anterior Approach Hepatectomy.

BACKGROUND/AIM: Studies have indicated that liver mobilization during hepatectomy could cause the dissemination of tumor cells. However, the data are still limited in terms of the relationship between circulating tumor cells (CTCs) and surgical procedures. PATIENTS AND METHODS: Fifteen patients who underwent hepatectomy for primary hepatocellular carcinoma (HCC) were included in the study. Blood samples were collected from the portal vein, central vein, and peripheral artery at three time points, namely, before mobilization (BM) of the liver, during transection (DT) of parenchyma, and after resection (AR) of the tumor. To detect CTCs, a real-time PCR assay was performed using primers for the epithelial cell adhesion molecule, cytokeratin 18, and glypican 3. Patients were divided into anterior approach (AA) and non-AA (NA) groups. In the AA group, patients underwent an initial hilar vascular dissection followed by a liver hanging maneuver during transection. RESULTS: Seven patients were allocated to the AA group, and eight to the NA group. In the NA group, CTC levels in the portal vein were significantly increased at DT and AR compared to BM. In cases with large HCC (>70 mm), CTC levels in central venous blood were significantly increased at DT and AR in the NA group. CONCLUSION: The AA liver resection technique may minimize CTC dissemination, improving the prognosis of patients with HCC.

Chitinase 3-like 1, Carcinoembryonic Antigen-related Cell Adhesion Molecule 6, and Ectopic Claudin-2 in the Carcinogenic Processes of Ulcerative Colitis.

BACKGROUND/AIM: The cumulative cancerous rate of colitis-associated cancer (CAC) has increased exponentially in patients with ulcerative colitis (UC). We have investigated the factors involved in the carcinogenic processes of CAC among UC patients. PATIENTS AND METHODS: A total of 42 UC patients who underwent surgical treatments between January 2001 and December 2010 at Kurume University Hospital (Fukuoka, Japan) were enrolled. We conducted this study using 3 cases of CAC out of 42 UC cases and 1 case of colorectal cancer. cDNA microarray analyses were performed using normal, inflamed, and cancerous tissues from surgical CAC specimens and protein expression was confirmed by immunohistochemical analyses. RESULTS: cDNA microarray revealed 32 genes that were dominantly expressed in tumorous regions of CAC. Gene ontology analysis revealed that these genes were involved in inflammatory responses and cytokine-cytokine receptor interactions. Chitinase 3-like1 (CHI3L1), carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), and Claudin-2 (CLND2) were selected from CAC-related genes as candidate molecules. Immunostaining revealed strong expression of each protein in cancerous regions. CONCLUSION: In this study, we identified CAC-related genes and found that CHI3L1, CEACAM6, and CLND2 were expressed in patient samples. All the above genes were associated with adherent invasive Escherichia coli (AIEC), which suggested that these molecules are likely involved in AIEC infection. Further analyses would be required to reveal unknown mechanisms of CAC-related genes in the tumor microenvironment.

Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study.

BACKGROUND: Complex interactions among endogenous and exogenous factors influence the incidence of colorectal cancer (CRC). Germline mutations in mismatch repair (MMR) genes causing Lynch syndrome (LS) are major endogenous factors. The exogenous factor, alcohol consumption, is potentially associated with CRC incidence among patients with LS. However, insufficient data are available to determine whether alcohol consumption influences the time of the first onset of CRC associated with sex, MMR gene mutations, and anatomical tumor site. METHODS: Among 316 patients with LS identified in a Japanese LS cohort, we included 288 with data on age, sex, proband status, alcohol status, smoking status, tumor location, and MMR gene mutations. Multivariable analysis assessed the association of alcohol consumption with earlier onset of the first CRC. RESULTS: Ever drinkers were associated with higher risk of the first onset of CRC than never drinkers (HR 1.54, 95%CI 1.14-2.07, P = 0.004). The association of the first onset of CRC with alcohol consumption was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations (vs those with pathogenic MSH6, PMS2 and EPCAM mutations), and tumors in the proximal colon cancer (vs distal colon and rectal cancer). CONCLUSIONS: Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.

[Retrospective Analysis of Treatment Strategies for Local Recurrence following Radical Resection of Rectal Cancer].

We report the findings from a retrospective study to determine the optimum treatment strategy for local recurrence following radical resection of rectal cancer. In our department, among all 430 patients that underwent radical resection of rectal cancer from 2012 to 2018, there were 28 patients that developed local recurrence. Of those patients, 12 underwent surgical treatment(Op group)and 16 did not(N-Op group). In the Op group, 8 patients underwent radical resection, of which 2 patients remained recurrence-free, and the other 6 patients developed recurrence. In the N-Op group, 6 patients were treated with systemic chemotherapy alone, a further 6 patients had palliative irradiation in addition to systemic chemotherapy, and the other 4 selected best supportive care(2 patients were treated with palliative irradiation). In the 8 patients who had palliative irradiation, 7 showed a decrease in numerical rating scale(NRS)after irradiation. The adverse events of palliative irradiation were scrotal dermatitis in 1 patient and perianal inflammation in another 3 patients. Our surgical results for local recurrence of rectal cancer in our department were worse in terms of recurrence rate, so these findings suggest that the preoperative surgical strategy could be reviewed, as well as the actual surgical methods such as the optimal circumferential resection margin. Palliative irradiation was found to be useful for pain control. However, the occurrence of adverse events remains a concern.

Diversity and shared T-cell receptor repertoire analysis in esophageal squamous cell carcinoma.

The tumor immune response is dependent on the interaction between tumor cells and the T-cell subset expressing the T-cell receptor (TCR) repertoire that infiltrates into the tumor microenvironment. The present study explored the diversity and shared TCR repertoires expressed on the surface of locoregional T cells and identified the T lymphocyte subsets infiltrating into esophageal squamous cell carcinoma (ESCC), in order to provide insight into the efficiency of immunotherapy and the development of a novel immune-oriented therapeutic strategy. A total of 53 patients with ESCC were enrolled in the present study, and immunohistochemical analysis of CD3, CD8, CD45RO, FOXP3, CD274, HLA class I and AE1/AE3 was performed. Digital pathological assessment was performed to evaluate the expression level of each marker. The clinicopathological significance of the immuno relation high (IR-Hi) group was assessed. Adaptor ligation PCR and next-generation sequencing were performed to explore the diversity of the TCR repertoire and to investigate the shared TCR repertoire in the IR-Hi group. Repertoire dissimilarity index (RDI) analysis was performed to assess the diversity of TCR, and the existence of shared TCRα and TCRß was also investigated. Further stratification was performed according to the expression of markers of different T-cell subsets. Patients were stratified into IR-Hi and immuno relation low (IR-Lo) groups. Cancer-specific survival and recurrence-free survival rates were significantly improved in the IR-Hi group compared with in the IT-Lo group. The diversity of the TCR repertoire was significantly higher in the IR-Hi group. TCR repertoire analysis revealed 27 combinations of TCRα and 23 combinations of TCRß VJ regions that were shared among the IR-Hi group. The IR-Hi group was divided into three clusters. Overall, the current findings revealed that the IR-Hi group maintained the diversity of TCR, and a portion of the IR-Hi cases held the T cells with shared TCR repertoires, implying recognition of shared antigens. The prognosis of patients with ESCC was affected by the existence of immune response cells and may possibly be stratified by the T-cell subsets.