Causal association between inflammatory bowel disease and 32 site-specific extracolonic cancers: a Mendelian randomization study.

BACKGROUND: The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers. METHODS: Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD patients, 5956 Crohn's disease (CD) patients, and 6968 ulcerative colitis (UC) patients. Three sources of cancer GWAS were selected as outcome data. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of IBD on 32 extracolonic cancers. The meta-analysis was applied to assess the combined causal effect with multiple MR results. RESULTS: IBD, CD, and UC have potential causal associations with oral cavity cancer (IBD: OR = 1.180, 95% CI: 1.059 to 1.316, P = 0.003; CD: OR = 1.112, 95% CI: 1.008 to 1.227, P = 0.034; UC: OR = 1.158, 95% CI: 1.041 to 1.288, P = 0.007). Meta-analysis showed a significant positive causal relationship between IBD and breast cancer (OR = 1.059; 95% CI: 1.033 to 1.086; P < 0.0001) as well as a potential causal relationship between CD and breast cancer (OR = 1.029; 95% CI: 1.002 to 1.055; P = 0.032) based on combining multiple MR results. CONCLUSIONS: This comprehensive MR analysis suggested that genetically predicted IBD, as well as its subtypes, may be a risk factor in the development of oral cavity and breast cancer.

Relative Risk of Bladder and Kidney Cancer in Lynch Syndrome: Systematic Review and Meta-Analysis.

Background: The association between Lynch syndrome (LS) and a higher risk of upper tract urothelial carcinoma is well established, but its effect on the risk of bladder and kidney cancers remains controversial. This review aimed to compare the relative risk (RR) of bladder and kidney cancer in confirmed LS germline mutation carriers compared to the general population. Methods: Medline, Embase, Cochrane Central, and Google Scholar were searched on 14 July 2022 for studies published in English that reported on the rates of urological cancer in adults with confirmed LS germline mutation. The quality of included studies was assessed using Cochrane's tool to evaluate risk of bias in cohort studies. Random effects meta-analysis estimated the pooled relative risk of bladder and kidney cancer in LS carriers compared to the general population. The quality of the overall evidence was evaluated using GRADE. Results: Of the 1839 records identified, 5 studies involving 7120 participants from 3 continents were included. Overall, LS carriers had a statistically significantly higher RR of developing bladder cancer (RR: 7.48, 95% CI: 3.70, 15.13) and kidney cancer (RR: 3.97, 95% CI: 1.23, 12.81) compared to unaffected participants (p < 0.01). The quality of the evidence was assessed as "low" due to the inclusion of cohort studies, the substantial heterogeneity, and moderate-to-high risk of bias. Conclusion: Lynch syndrome is associated with a significant increase in the relative risk of kidney and bladder cancer. Clinicians should adopt a lower threshold for germline mutation genetic testing in individuals who present with bladder cancer. Further studies evaluating the role and cost-effectiveness of novel urine-based laboratory tests are needed. High-quality studies in histologically proven renal cell carcinoma and their underlying germline mutations are necessary to strengthen the association with LS.

Risk of cancer in individuals with Lynch-like syndrome and their families: a systematic review.

BACKGROUND: Lynch-like syndrome (LLS) tumors have similar clinicopathological features to Lynch syndrome (LS) tumors but have no identifiable pathogenic germline mismatch repair gene variant. However, cancer risks in LLS patients and first-degree relatives (FDRs) are not well defined. METHODS: To clarify LLS-associated cancer risks, a systematic review of all studies examining all cancer risks in LLS was performed. Searching of Medline, Embase, Pubmed, Cochrane and CINAHL databases and reference/citation checking identified relevant studies published between January 1, 1980 and February 11, 2021. Joanna Briggs Institute Appraisal Tools assessed the risk of bias. RESULTS: Six studies (five cohort/one cross-sectional) were eligible for study inclusion. One study found no difference in colorectal cancer (CRC) incidence between LLS and LS patients or CRC risks at aged 70 years. Three studies found CRC incidence in LLS FDRs was higher than the general population but lower than LS FDRs. Two studies showed no difference in CRC diagnosis age between LLS patients and LS patients. Endometrial cancer risks in LLS patients were higher than the general population but lower than LS patients. CONCLUSION: Evidence of elevated CRC risks in LLS patients and FDRs supports increased colonoscopy surveillance strategies for LLS patients and FDRs in line with current recommendations for LS. Due to heterogeneity amongst LLS populations, extended intervals between screening may be advised for low-risk families. Studies to resolve the molecular characterization and definition of LLS are needed to clarify cancer risks associated with LLS which in turn may individualize surveillance strategies for LLS patients and families.

Metastatic undifferentiated pleomorphic sarcoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Pathological differentiation is important for suspected lesions of metastatic undifferentiated pleomorphic sarcoma (UPS) because no reliable imaging criteria exist for this entity yet. In the present case, transgastric endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the pancreatic tumor and transcolonic EUS-FNA for the intraabdominal tumor contributed to the definitive diagnosis of metastatic UPS, leading to appropriate treatment selection.

Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis.

Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-ß, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation.

Reevaluating the Evidence for Intensive Postoperative Extracolonic Surveillance for Nonmetastatic Colorectal Cancer.

OBJECTIVES: The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful. METHODS: A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy. RESULTS: For all 3 trials, the model predicted a mortality reduction of ≤5% and power of <10%. The FACS recurrence imbalance likely led to a large relative bias (>2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P>.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients. CONCLUSIONS: Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

The bowel and beyond: extracolonic findings from CT colonography.

CT colonography has emerged as the investigation of choice for suspected colorectal cancer in patients when a colonoscopy in incomplete, is deemed high risk or is declined because of patient preference. Unlike a traditional colonoscopy, it frequently reveals extracolonic as well as colonic findings. Our study aimed to determine the prevalence, characteristics and potential significance of extracolonic findings on CT colonography within our own institution. A retrospective review was performed of 502 patients who underwent CT colonography in our institution between January 1, 2010 and January 4, 2015. Of 502 patients, 60.63% had at least one extracolonic finding. This was close to other similar-sized studies (Kumar et al. Radiology 236(2):519-526, 2005). However, our rate of E4 findings was significantly higher than that reported in larger studies at 5.3%(Pooler et al. AJR 206:313-318, 2016). The difference may be explained by our combination of symptomatic/screening patients or by the age and gender distribution of our population. Our study lends support to the hypothesis that CT colonography may be particularly useful in identifying clinically significant extracolonic findings in symptomatic patients. CT colonography may allow early identification of extracolonic malignancies and life-threatening conditions such as an abdominal aortic aneurysm at a preclinical stage when they are amenable to medical or surgical intervention. However, extracolonic findings may also result in unnecessary investigations for subsequently benign findings.

Risk of extracolonic malignancies and metachronous rectal cancer after colectomy and ileorectal anastomosis in familial adenomatous polyposis.

BACKGROUND: Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients. METHODS: Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed. RESULTS: The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer. CONCLUSION: Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients.

A novel Lynch syndrome pedigree bearing germ-line MSH2 missense mutation c.1808A>T (Asp603Val).

We report the first pedigree of Lynch syndrome bearing a germ-line MSH2 missense mutation c.1808A>T (Asp603Val). Until now, this missense mutation, in exon 12 of MSH2, was identified as a variant of unknown significance in the International Society for Gastrointestinal Hereditary Tumours database. In vitro induction mutagenesis experiments indicated that the MSH2 mutant protein (Asp603Val) is easily degraded in embryonic stem cells, albeit there is no clinical information concerning this mutant. Our pedigree includes four patients with Lynch syndrome-associated malignancies and clinically matches the Amsterdam II criteria. The proband, a female, first had an endometrial cancer at the age of 49 and then mantle cell lymphoma, colonic and gastric adenocarcinomas and neuroendocrine carcinoma, successively. Her mother also had Lynch syndrome-associated malignancies, including colonic, uterine and gastric cancers, and her elder son had rectal cancer. In the germline of the proband and her son, an MSH2 missense mutation c.1808A>T was discovered. Immunohistochemical analyses indicated that the expression of the MSH2 protein was decreased in the tumors, such as gastric cancer and neuroendocrine carcinoma, due to the missense mutation c.1808A>T. This study showed that the MSH2 missense mutation c.1808A>T (Asp603Val) is a likely pathogenic mutation and is responsible for typical Lynch syndrome-associated malignancies, including neuroendocrine carcinoma.

Lynch Syndrome-Associated Cancers Beyond Colorectal Cancer.

Lynch syndrome (LS) is a common form of inherited cancer susceptibility, which predisposes to colorectal cancer (CRC) along with a wide array of other extracolonic malignancies, including other gastrointestinal cancers, cancers of the gynecologic and genitourinary tracts, and other organ sites. Recent data have provided novel insights into patient-specific factors that can help clinicians understand an individual LS carrier's risk of extracolonic cancers, including sex, specific LS gene, age, family history of cancer, and other factors. This summary seeks to provide an update on extracolonic cancer risks in LS and provide recommendations for surveillance and risk reduction.

Implications of colonic and extra-colonic findings on CT colonography in FIT positive patients in the Dutch bowel cancer screening program.

OBJECTIVES: In the Dutch National colorectal cancer (CRC) screening program, patients with a positive faecal immunochemical test (FIT) are referred for a colonoscopy. In a small proportion, because of contraindications, a computed tomographic colonography (CTC) is performed to rule out advanced neoplasia. The aim of our study is to evaluate the intra- and extra-colonic yield of CTC and its clinical implications. MATERIALS AND METHODS: In this retrospective cohort study, all FIT positive patients who underwent primary (instead of colonoscopy) or secondary CTC (after incomplete colonoscopy) between January 2014 and January 2018 were included. Relevant intra-colonic lesions on CTC were defined as lesions suspected for CRC or >10 mm. Relevant extra-colonic findings were defined as E3 and E4 using the E-RADS classification. RESULTS: Of the 268 included patients, 66 (24.6%) were suspected to have CRC or 10 mm + lesion on CTC and 56 of them (84.8%) underwent an additional endoscopy. Another 20 patients with <10 mm lesions on CTC underwent additional endoscopy. Overall, 76/268 patients (28.4%) underwent confirmatory endoscopy of which 50 (18.7%) had histologic confirmed advanced neoplasia; 4.9% had CRC and 13.8% advanced adenoma. New relevant extra-colonic findings were detected in 13.8%. CONCLUSIONS: In the Dutch National CRC screening program, a CTC was followed by an endoscopic procedure in more than a quarter of patients, resulting in a significant number of advanced neoplasia. Overall, one out of seven CTCs showed new relevant extra-colonic findings which may lead to further diagnostic/therapeutic work-up. Our results can be important for the informed consent procedure.

Comparison of the efficacy of self-expandable metallic stents in colorectal obstructions caused by extracolonic malignancy and colorectal cancer.

The current study aimed to compare the safety and effectiveness of self-expandable metallic stent placement among patients with extracolonic malignancy and those with colorectal cancer. Patient information, technical and clinical success rates and complication rates were compared between patients with colorectal cancer and extracolonic malignancy. The Kaplan-Meier method was used to compare the time elapsed before the onset of complications. Risk factors for re-obstruction in patients with self-expandable metallic stents were evaluated by multivariate analysis. A total of 68 patients who underwent self-expandable metallic stent placement at Saiseikai Niigata Hospital between January 2012 and September 2019 were included. The clinical success rate was significantly different between the colorectal cancer (96.6%) and extracolonic malignancy (66.7%) groups (P=0.01). The incidence of complications was significantly higher in the extracolonic malignancy group (66.7%) than in the colorectal cancer group (25.4%; P=0.02). Additionally, the time elapsed before the onset of complications was shorter in the extracolonic malignancy group than in the colorectal cancer group (P=0.0008). Risk factors for re-obstruction were higher in the extracolonic malignancy group [odds ratio, 7.76 (1.02-57.2)] than in the palliative stent placement group [odds ratio, 5.45 (1.01-29.5); P=0.04]. In extracolonic malignancy, self-expandable metallic stent placement was associated with lower clinical success rates and increased risk of complications. The time elapsed before the onset of complications was short, and extracolonic malignancy was a risk factor for re-obstruction, suggesting that the placement of self-expandable metallic stents for malignant colorectal obstruction in extracolonic malignancy is not optimal.

Familial Burden and Other Clinical Factors Associated With Various Types of Cancer in Individuals With Lynch Syndrome.

BACKGROUND & AIMS: Lynch syndrome (LS) is associated with increased risks of various gastrointestinal, gynecologic, genitourinary, and other cancers. Many clinical practice guidelines recommend that LS carriers' screening strategies be devised based on their family history of various cancers, in addition to age-, sex-, and gene-specific considerations. The aim of this study was to examine the association between family history and other clinical factors with LS carriers' histories of various cancers. METHODS: Two cohorts of LS carriers were analyzed: a laboratory-based cohort of consecutively ascertained individuals undergoing germline LS testing and a clinic-based cohort of LS carriers undergoing clinical care at an academic medical center. Multivariable logistic regression was performed to assess clinical factors associated with LS carriers' histories of various cancers/neoplasms. Familial burden was defined as LS carriers' aggregate number of first-/second-degree relatives with a history of a given malignancy. RESULTS: Multivariable analysis of the laboratory-based cohort (3828 LS carriers) identified familial burden as being incrementally associated with LS carriers' personal history of endometrial (odds ratio [OR], 1.37 per affected first-/second-degree relative; 95% confidence interval [CI], 1.21-1.56), urinary tract (OR, 2.72; 95% CI, 2.02-3.67), small bowel (OR, 3.17; 95% CI, 1.65-6.12), gastric (OR, 1.93; 95% CI, 1.24-3.02), and pancreaticobiliary cancers (OR, 2.10; 95% CI, 1.21-3.65) and sebaceous neoplasms (OR, 7.39; 95% CI, 2.71-20.15). Multivariable analysis of the clinic-based cohort (607 LS carriers) confirmed a significant association of familial burden of endometrial and urinary tract cancers. CONCLUSIONS: Familial burden - in addition to age, sex, and specific LS gene - should be used to assess LS carriers' risks of specific cancers and guide decision-making about organ-specific surveillance.

Clostridioides difficile from intracardiac vegetation.

Extracolonic manifestations by Clostridioides difficile are uncommon. Here, we report a case of monomicrobial C. difficile intracardiac vegetation in a 11-year-old girl with a predisposed heart disease who responded well to the treatment. C. difficile has been isolated from a variety of specimens outside the intestinal tract and is not always associated with gastrointestinal symptoms.

Clostridium difficile appendicitis in an immunocompromised patient: a case report and review of the literature.

BACKGROUND: Clostridium difficile (C. difficile) is a common cause of infectious colitis in individuals with prior antibiotic or hospital exposure. Extraintestinal manifestations of C. difficile infections, however, are rare. Here we present a case of C. difficile appendicitis in an immunocompromised patient. CASE PRESENTATION: A 53-year-old Caucasian male presented to the emergency room for two days of lower abdominal pain associated with nausea and subjective fevers. He otherwise denied having diarrhea or hematochezia. He did not have any recent hospitalizations, nursing home stays, or antibiotic exposure. His past medical history was notable for stage III tonsillar squamous cell carcinoma for which he was status post tonsillectomy, radiation therapy, and chemotherapy (cisplatin 4 days prior to presentation). He was afebrile with tenderness to palpation in the bilateral lower quadrants, right greater than left. His white blood cell (WBC) count was 15.6 × 103 cells/µL. Computed tomography (CT) of the abdomen and pelvis showed marked edema and inflammation of the cecum and ascending colon as well as an enlarged appendix with surrounding inflammatory changes with a small amount of free fluid in the right paracolic gutter. He was treated non-surgically with antibiotics. He did not clinically improve and on hospital day 3, he developed diarrhea for which C. difficile stool polymerase chain reaction was sent. Repeat CT of the abdomen and pelvis was performed which showed progression to pan-colitis and persistent appendicitis. C. difficile testing later resulted positive, for which oral vancomycin was started. The patient markedly improved with medical management alone and was subsequently discharged on oral vancomycin. CONCLUSIONS: Our case highlights the importance of maintaining a high index of suspicion for C. difficile in a patient presenting with both appendicitis and colitis, with prompt diagnosis and treatment being essential.

Efficacy of uncovered self-expandable metallic stent for colorectal obstruction by extracolonic malignancy.

BACKGROUND: Self-expandable metallic stent (SEMS) is widely used for malignant colorectal obstruction. Recently, SEMS has been used for palliative option for colorectal obstruction caused by extracolonic malignancy (ECM). AIM: To evaluate the efficacy of SEMS for colorectal obstruction caused by ECM, and to identify the factors associated with stent occlusion. METHODS: Seventy-two patients who were treated with uncovered SEMS insertion for malignant colorectal obstructions caused by colorectal metastasis or peritoneal seeding of ECM at Samsung Medical Center between April 2012 to March 2016 were enrolled. We analyzed technical and clinical outcomes of stent insertion, the factors associated with stent occlusion and long term outcomes after stent insertion. RESULTS: Technical success rate was determined as 90.3% with a clinical success rate of 87.7%. Stent occlusion developed in 28.1%, with a median duration of 51 d. Further, 81.3% with stent occlusion could be treated with secondary stent insertion. Clinical failure was observed to be related to the male sex (P = 0.020) and right colon obstruction (P = 0.017). Stent length ≤ 10 cm was found to be associated with stent occlusion (P = 0.003). Median survival time after stent insertion was 4.7 mo and 40.4% were able to receive their oncological treatments after stent insertion without surgery. CONCLUSION: Uncovered SEMS is effective for the treatment of colorectal obstruction caused by ECM, considering life expectancy of patients with ECM.

An incidental finding of pheochromocytoma in a 33-year-old patient with Lynch syndrome.

Pheochromocytoma is a catecholamine-producing neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. The detection of these tumors is extremely important because they are associated with high cardiovascular morbidity and mortality. Progress in molecular genetics has revealed that up to 35% of pheochromocytomas are inhereted. Lynch syndrome (hereditary nonpolypous colorectal cancer - HNPCC) is an autosomal dominant genetic condition that is associated with a high risk of colorectal cancer or other extracolonic tumors (adenocarcinoma of endometrium, stomach, ovarian carcinoma, carcinoma of urinary tract, small intestine, brain tumors and skin cancer). Foreign medical journals are reporting an increasing number of cases on coexistence of HNPCC and neuroendocrine tumors, including pheochromocytoma. It increases the likelihood that this type of tumor could represent an additional extracolonic manifestation of Lynch syndrome.

Different surgical outcome and follow-up status between dMMR and pMMR colorectal cancer patients who fulfilled with Amsterdam-II criteria.

BACKGROUND: Although hereditary non-polyposis colorectal cancer (HNPCC) could be subtyped into proficient or deficient mismatch repair gene expression (pMMR or dMMR), distinct clinical features between these two subgroups patients were rarely reported. METHODS: We retrospectively analyzed 175 hereditary non-polyposis colorectal cancer (HNPCC) patients between January 1995 and December 2012. Cox proportional hazards model was used to compare the differences between two subgroups. RESULTS: Significant differences of disease free survival (DFS) and overall survival (OS) exist between dMMR and pMMR. In addition to other factors including younger mean age of diagnosis for dMMR patients (48.6 years vs. 54.3 years), operation type (more extended colectomy for dMMR 35.8% vs. 14.5%), tumor location (right colon predominance for dMMR 61.7% vs. 27.3% and more rectum cases for pMMR 41.8% vs. 11.7%), tumor differentiation (more poor differentiation for dMMR 23.3% vs. 9.0%), N staging (more N0 cases for dMMR 70.8% vs. 50.9%), more frequently presence of extra-colonic tumors for dMMR (16.7% vs.1.8%), and lower recurrence rates (9.1% vs.35.3%). Significantly different cumulative incidences of developing metachronous colorectal cancer were observed with 6.18 for pMMR patients and 20.57 person-years for dMMR patients (p < 0.001). CONCLUSIONS: Distinct clinicopathological features significantly exist between dMMR and pMMR subtypes patient, MMR status should be consider to tailor operation types and follow up surveillance between these two subgroups patients who all fulfilled with Amsterdam-II criteria.

Spectrum and Frequency of Tumors, Cancer Risk and Survival in Chilean Families with Lynch Syndrome: Experience of the Implementation of a Registry.

Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p < 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.

Stenting as a bridge to surgery for extra-colonic malignancy induced colorectal obstruction: preliminary experience.

BACKGROUND: The majority of colonic obstructions result from colorectal cancer. However, malignancies of extra-colonic origin can also disrupt colorectal patency, and the efficacy of self-expanding metal stents (SEMS) insertion as a bridge to surgery in these patients are still in debate. The aim of this study is to evaluate the efficacy of endoscopic stenting as a bridge to surgery (BTS) for extra-colonic malignancy (ECM)-induced colonic obstruction. METHODS: Thirty-three patients with colonic obstruction due to ECM who received self-expanding metal stents (SEMS) insertion at a single academic tertiary medical center between 2004 and 2015 were included. The purpose of SEMS insertion was determined based on whether the patient's medical records indicated any surgical plans before SEMS insertion. Technical success was defined as a patent SEMS covering the entire length of the obstruction. Bridging success was defined as elective surgical procedures after the first SEMS insertion. RESULTS: Among the 33 patients who underwent SEMS insertion for colorectal obstruction due to ECM, nine underwent SEMS as a BTS. Technical success was achieved in 100% (9/9). Seven patients underwent elective surgery after successful decompression with the first SEMS, and the bridging success rate was 77.8% (7/9). Two patients needed secondary stent insertion before elective surgery. However, none of them required emergent surgery. No major complications occurred, including death related to colorectal endoscopic procedures, perforation, or bleeding. CONCLUSION: SEMS insertion as a BTS is a good treatment option to avoid emergent surgery in patients with colonic obstruction caused by extra-colonic malignancy.