Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50%) and MSH2 (40%), while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

BackgroundGenetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. MethodsEleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome.ResultsWe performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet.ConclusionThe Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.

Exclusive CRT approach is not safe to treat patients with low infiltrative rectal carcinoma.

Background It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient’s response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of “clinical-benefit.” To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower GI tract polyposis. Methods Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case using the proposed system and chose a stage-specific intervention for each case. Our endpoint was degree of concordance among reviewers staging and intervention assessments. Results The stage and intervention ratings of the 26 reviewers were highly concordant (ρ= 0.710; 95% credible interval, 0.651–0.759). Sixty-two percent of reviewers agreed on FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. Conclusions The proposed FAP colon polyposis staging system and stage-specific intervention is based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.

The increase in colorectal cancer mortality remained significant when assessing Brazil as a whole only among men; in seven States among men, and in nine States among women, regardless of the studied indicators. These differences could be related to the possible increase in incidence and to late access to diagnosis and treatment.

The impact of clinical, pathologic, and surgical variables on the postoperative morbidity, mortality, and survival of patients undergoing extended resections of colon carcinoma were evaluated.METHODS: The medical records of 95 patients who underwent extended resections for colon carcinoma between 1953 and 1996 were reviewed. In all cases, in addition to colectomy, 1 or more organs and/or structures were resected en bloc due to a macroscopically based suspicion of tumor invasion. The clinical, pathologic, and surgical parameters were analyzed. Overall survival rates were analyzed according to the method of Kaplan and Meier. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Eighty-six patients were treated by curative surgeries and the remaining by palliative resections. Invasion of the organs and/or adjacent structures and regional lymph nodes was found microscopically in 48 and 31 patients, respectively. The median follow-up without postoperative mortality was 47.7 months. The 5-year overall survival rates was 52.6%. The 5-year overall survival rates for patients undergoing curative and palliative surgeries was 58.3% and 0%, respectively. The mean survival time in the palliative surgery group was 3.1 months. Multivariate analysis showed that Karnofsky performance status was strongly related to the risk of postoperative complications (P = .01), and postoperative deaths were associated with the type of surgery and Karnofsky performance status at the time of admission (P = .001).CONCLUSIONS: Some patients with locally advanced colon adenocarcinomas undergoing extended resections have a 5-year overall survival rates of 58.3%. Patients could benefit from palliative-intent procedures, but these measures should cautiously be indicated and avoided in patients with low Karnofsky performance status due to high rates of postoperative mortality and poor survival.

Catalona's procedure was not reliable. We therefore recommend standard inguinal lymphadenectomy as the minimal treatment for patients with infiltrating carcinoma of the penis.

We assessed the reliability of anorectal angle (ARA) measurement as an index of fecal incontinence. The "posterior" ARA was measured at rest, squeezing, and straining in 69 continent and 82 incontinent subjects all complaining of various evacuation dysfunctions. The two groups were homogeneous with regard to sex distribution (48.6% vs. 51.4% men and 44.7% vs. 55.3% women, n.s.) and age (56.5 +/- 10.2 vs. 59.3 +/- 9.7 years, n.s.). The incidence of rectal prolapse was the same in the two groups (40 each). The intraobserver agreement index from two independent measurements (Pearson's correlation coefficient), age, and gender interaction [T2 Hotelling test in multivariate analysis of variance (ANOVA)] and the most discriminating category of ARA measurement (Fisher's F test in ANOVA) were calculated. In addition, the relationship between ARA and severity of incontinence was assessed by the eta coefficient. Pearson's correlation coefficient was between 0.78 and 0.98 (P < 0.01). The mean ARA differed significantly between the continent and incontinent subjects (104.5 +/- 10.3 degrees vs. 116.2 +/- 23.6 degrees at rest, 84.5 +/- 14.2 degrees vs. 95.1 +/- 20.1 degrees on squeezing, and 133.7 +/- 21.7 degrees vs. 141.7 +/- 25.9 degrees on straining; T2 0.066, P < 0.05 in multivariate ANOVA). No interaction was noted between groups and gender (T2 = 0.023; F = 1.11, n.s.). Resting ARA was shown by ANOVA to be the most discriminating index (F = 9.4 P < 0.01) between the two groups. Overall, ARA measurement was correlated with the severity of fecal incontinence (eta coefficient: 0.894 at rest; 0.811 on squeezing; 0.695 on straining); its accuracy was 79%, the false-positive rate was 15.3% and the false-negative rate 26.5%. Irrespective of the underlying abnormality, namely rectal prolapse, ARA measurement by defecography can: (a) be reinterpreted reliably by the same observer and (b) differentiate continent from incontinent subjects.