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Purpose:No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy (“Watch-and-Wait”).Experimental Design:Biopsies from two independent cohorts (n1 = 131, n2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait.Results:ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06–0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the “Watch-and-Wait” cohort (n = 73), no relapse was observed in patients with ISB high (23.3%).Conclusions:ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.

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Summary Background Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy. Methods We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years. Findings We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0–75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8–90·9), for 3 years was 97·3% (95·2–98·6), and for 5 years was 98·6% (97·6–100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3–95·9), for 3 years was 97·8% (96·6–99·3), and for 5 years was 96·6% (94·0–98·9). Interpretation These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach. Funding European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d’HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.

Colorectal anastomotic stricture is a frequent complication that may affect up to 30% of patients. However, a complete obstruction is rare. Endoscopic balloon dilation is the first-line therapy, but it invariably requires being able to cross the stricture with the dilation device. When this is not possible, surgical revision is the alternative, but it is associated with higher morbidity. A 76-year-old male patient underwent an urgent high anterior resection with transverse loop colostomy for an occlusive high rectal tumor. On postoperative day 8, he presented with anastomotic leakage and abscess formation, requiring percutaneous drainage. Ten months after surgery, a colonoscopy revealed a complete stricture of the anastomosis, refractory to negotiation of a guide wire, thus precluding balloon dilation. Hence, a modified rendezvous technique was planned. Simultaneously, a flexible endoscope and a rigid rectoscope were progressed through the distal loop colostomy, and the anus, respectively. A needle device was introduced through the rectoscope and used to pierce the colonic stump. A guide wire was progressed, and the stricture was dilated with a controlled radial expansion balloon catheter. Finally, a 12-Fr Foley catheter was left through the anastomosis. A total of three endoscopic balloon dilation sessions were completed, and successful colostomy reversal was carried out 10 days after the last session. Fluoroscopy-endoscopy-guided recanalization is an effective and safe treatment option for complete colorectal anastomotic stricture.

Germline pathogenic variants in the DNA mismatch repair genes (MMR): MLH1, MSH2, MSH6, and PMS2, are causative of Lynch syndrome (LS). However, many of the variants mapping outside the invariant splice site positions (IVS ± 1, IVS ± 2) are classified as variants of unknown significance (VUS). Three such variants (MLH1 c.588+5G>C, c.588+5G>T and c.677+5G>A) were identified in 8 unrelated LS families from Argentina, Brazil and Chile. Herein, we collected clinical information on these families and performed segregation analysis and RNA splicing studies to assess the implication of these VUS in LS etiology. Pedigrees showed a clear pattern of variant co-segregation with colorectal cancer and/or other LS-associated malignancies. Tumors presented deficient expression of MLH1-PMS2 proteins in 7/7 of the LS families, and MSI-high status in 3/3 cases. Moreover, RNA analyses revealed that c.588+5G>C and c.588+5G>T induce skipping of exon 7 whereas c.677+5G>A causes skipping of exon 8. In sum, we report that the combined clinical findings in the families and the molecular studies provided the evidences needed to demonstrate that the three MLH1 variants are causative of LS and to classify c.588+5G>C and c.677+5G>A as class 5 (pathogenic), and c.588+5G>T as class 4 (likely-pathogenic). Our findings underline the importance of performing clinical and family analyses, as well as RNA splicing assays in order to determine the clinical significance of intronic variants, and contribute to the genetic counseling and clinical management of patients and their relatives.

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.

Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p 0 center dot 0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and onlyBackground Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero. Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and only 10-19% having a penetrance of 40-60%. Interpretation Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome. Funding National Health and Medical Research Council, Australia. Copyright (c) 2021 Elsevier Ltd. All rights reserved.Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency. Radium Hospital Foundation (Oslo, Norway)

Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery.Conclusion: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene-and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syn-drome to improve outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd.

Purpose To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR ( path_MMR ) variants. Methods The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Results Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1 , path_MSH2 , path_MSH6 , and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. Conclusion Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

Aim: We investigated the role of maternal ancestry in neoplastic hematological malignancies (HMs) risk in a population from Central Argentina. Materials & methods: We analyzed 125 cases with HMs and 310 controls from a public hospital, and a set of 202 colorectal, breast, lung, and hematologic cancer patients from a private hospital. Results: A decreased risk for HMs was associated with the Native American haplogroup B2 (odds ratio = 0.49; 95% CI: 0.25–0.92; p = 0.02). The sub-Saharan African parahaplogroup L was associated with higher susceptibility for disease (odds ratio = 3.10; 95% CI: 1.04–9.31; p = 0.043). Although the mean ancestral proportions in the total studied population was as published (61.7% Native American, 34.6% European and 3.7% African), an unequal distribution was observed between hospitals. Conclusion: We confirmed the tri-hybrid nature of the Argentinean population, with proportions varying within the country. Our finding supports the notion that associated haplogroup is population and cancer specific.

Background The incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a ‘resource-light’ sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries. Methods We assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries. Next, to determine the effect of prolonged UK storage, DNA extraction replicates for a subset of samples were performed up to 252 days apart. To profile the CRC-associated microbiome of developing countries, gFOBT were collected from 41 treatment-naïve CRC patients and 40 non-CRC controls from across the four institutes, and V4 16S rRNA gene sequencing was performed. Finally, we constructed a random forest (RF) model that was trained and tested against existing datasets from developed countries. Results The microbiome was stably assayed when samples were stored/transported at room temperature and after prolonged UK storage. Large-scale microbiome structure was separated by country and continent, with a smaller effect from CRC. Importantly, the RF model performed similarly to models trained using external datasets and identified similar taxa of importance (Parvimonas, Peptostreptococcus, Fusobacterium, Alistipes, and Escherichia). Conclusions This study demonstrates that gFOBT, stored and transported at room temperature, represents a suitable method of faecal sample collection for amplicon-based microbiome biomarkers in developing countries and suggests a CRC-faecal microbiome association that is consistent between developed and developing countries.

Colorectal anastomotic stricture is a frequent complication that may affect up to 30% of patients. However, a complete obstruction is rare. Endoscopic balloon dilation is the first-line therapy, but it invariably requires being able to cross the stricture with the dilation device. When this is not possible, surgical revision is the alternative, but it is associated with higher morbidity.A 76-year-old male patient underwent an urgent high anterior resection with transverse loop colostomy for an occlusive high rectal tumor. On postoperative day 8, he presented with anastomotic leakage and abscess formation, requiring percutaneous drainage. Ten months after surgery, a colonoscopy revealed a complete stricture of the anastomosis, refractory to negotiation of a guide wire, thus precluding balloon dilation. Hence, a modified rendezvous technique was planned. Simultaneously, a flexible endoscope and a rigid rectoscope were progressed through the distal loop colostomy, and the anus, respectively. A needle device was introduced through the rectoscope and used to pierce the colonic stump. A guide wire was progressed, and the stricture was dilated with a controlled radial expansion balloon catheter. Finally, a 12-Fr Foley catheter was left through the anastomosis. A total of three endoscopic balloon dilation sessions were completed, and successful colostomy reversal was carried out 10 days after the last session.Fluoroscopy-endoscopy-guided recanalization is an effective and safe treatment option for complete colorectal anastomotic stricture.

Lynch syndrome (LS) results from pathogenic variants in the mismatch repair (MMR) genes and is the most common hereditary cancer syndrome, affecting an estimated 1 in 300 individuals. Pathogenic variants in each of the MMR genes path_MLH1, path_MSH2, path_MSH6, and path_PMS2 result in different risks for cancers in organs including the colorectum, endometrium, ovaries, stomach, small bowel, bile duct, pancreas, and upper urinary tract. Accurate estimates of these risks are essential for planning appropriate approaches to the prevention or early diagnosis of cancers but the robustness of previous studies has been limited by factors including retrospective design,1,2 lack of validation in independent cohorts,3-5 and inconsistent classification of genetic variants. Unexpected findings from previous studies have included path_MLH1 and path_MSH2 carriers appearing to have a lifetime risk of colorectal cancer (CRC) of approximately 50%, despite surveillance colonoscopy,6-8 and that shorter intervals between colonoscopies do not seem to reduce the incidence of CRC in LS.9,10 These findings challenge the assumptions that CRC in LS usually develops from a noninfiltrative adenoma precursor and that CRC can be prevented by colonoscopic detection and removal of adenomas in the colon and rectum. Additionally, previous studies in the Prospective Lynch Syndrome Database (PLSD) have shown no increase in cancer risk in path_PMS2 carriers before 40 years of age and, although observation years were limited in older path_PMS2 carriers, LS-associated cancers other than endometrial and prostate were not observed.6-8 In this study we collected prospective data from a new large cohort of path_MMR carriers to validate previous findings from PLSD. We also updated information on the original cohort to ensure consistent classification of pathogenicity of MMR gene variants. We then combined both data sets, providing larger numbers that allowed us to derive more precise risk estimates for cancers in LS categorized by gene and gender.

Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy (“Watch-and-Wait”). Experimental Design: Biopsies from two independent cohorts (n1 = 131, n2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. Results: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06–0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the “Watch-and-Wait” cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). Conclusions: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.

BACKGROUND: The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait Database (IWWD) aims to describe the outcome of the W&W strategy in a large-scale registry of pooled individual patient data. We report the results of a descriptive analysis after inclusion of more than 1000 patients in the registry.METHODS: Participating centres entered data in the registry through an online, highly secured, and encrypted research data server. Data included baseline characteristics, neoadjuvant therapy, imaging protocols, incidence of local regrowth and distant metastasis, and survival status. All patients with rectal cancer in whom the standard of care (total mesorectal excision surgery) was omitted after neoadjuvant therapy were eligible to be included in the IWWD. For the present analysis, we only selected patients with no signs of residual tumour at reassessment (a cCR). We analysed the proportion of patients with local regrowth, proportion of patients with distant metastases, 5-year overall survival, and 5-year disease-specific survival.FINDINGS: Between April 14, 2015, and June 30, 2017, we identified 1009 patients who received neoadjuvant treatment and were managed by W&W in the database from 47 participating institutes (15 countries). We included 880 (87%) patients with a cCR. Median follow-up time was 3·3 years (95% CI 3·1-3·6). The 2-year cumulative incidence of local regrowth was 25·2% (95% CI 22·2-28·5%), 88% of all local regrowth was diagnosed in the first 2 years, and 97% of local regrowth was located in the bowel wall. Distant metastasis were diagnosed in 71 (8%) of 880 patients. 5-year overall survival was 85% (95% CI 80·9-87·7%), and 5-year disease-specific survival was 94% (91-96%).INTERPRETATION: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data. Local regrowth occurs mostly in the first 2 years and in the bowel wall, emphasising the importance of endoscopic surveillance to ensure the option of deferred curative surgery. Local unsalvageable disease after W&W was rare.FUNDING: European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant.

Microsatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included. BAT26 determination was performed in all cases; if instability was found, immunohistochemistry (IHC) and BRAF mutation analyses were done, as appropriate. Differences were assessed by chi-squared or Fisher’s exact test, or by T test or Mann–Whitney. Multiple logistic regression was used to identify factors independently associated with BAT26-unstable tumors. We included 155 patients; mean age was 65.6 (SD 14.4) and 56.1% were male. The frequency of BAT26-unstable tumors was 22% (95% CI 15.7–29.3). Factors independently associated with BAT26-unstable tumors were right colon localization (OR 3.4, 95% CI 1.3–8.7), histological MSI features (OR 5.1, 95% CI 1.9–13.6) and Amsterdam criteria (OR 23.2, 95% CI 1.9–286.7). IHC was altered in 85.3% BAT26-unstable tumors and 70.6% lacked MLH1 expression; 47.8% of these harbored BRAF V600E mutation. We provide evidence to link the frequency of BAT26 to an increased diagnostic yield (up to 1.4-folds) of suspected LS cases in comparison to the revised Bethesda guidelines alone. In regions with limited resources, clinical and histological features associated with BAT26-unstable status could be useful to direct MSI screening in sporadic CRCs and may help guide clinical care and future research. Fil: González, María Laura. Hospital Italiano; Argentina Fil: Causada Calo, Natalia. Hospital Italiano; Argentina. McMaster University; Canadá Fil: Santino, Juan Pablo. Hospital Italiano; Argentina Fil: Dominguez Valentin, Mev. The Norwegian Radium Hospital; Noruega Fil: Ferro, Fabiana Alejandra. Hospital Italiano; Argentina Fil: Sammartino, Inés. Hospital Italiano; Argentina Fil: Kalfayan, Pablo Germán. Hospital Italiano; Argentina Fil: Verzura, Maria Alicia. Hospital Italiano; Argentina Fil: Piñero, Tamara Lejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina Fil: Cajal, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina Fil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina Fil: Vaccaro, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina

RESUMEN La Poliposis Adenomatosa Familiar (PAF) y el Sindrome de Lynch (SL) son los dos sindromes hereditarios mas importantes que predisponen al cancer colorrectal (CCR). La PAF surge de mutaciones en el gen APC, y causa CCR en todos los portadores despues de los 40 anos. La enfermedad se expresa desde la adolescencia y puede ser tratado con cirugia profilactica. Como otras causas de muerte en pacientes con PAF se observan el cancer periampular y los tumores desmoides. En cambio, el SL es causado por mutaciones en los genes de reparacion del DNA, mas frecuentemente MLH 1, MSH 2 y MSH 6. El diagnostico clinico se basa en los criterios de Amsterdam. La penetrancia en portadores para CCR es incompleta, por lo que la colectomia profilactica es controvertida. El SL se asocia con alta frecuencia a otros tipos de tumores, como el cancer de endometrio, cancer de ovario y cancer de urotelio entre otros. En ambos sindromes, el estudio genetico de los pacientes permite en altos porcentajes identificar las mutaciones causantes. En base a estos resultados, se pueden identificar los familiares portadores de mutaciones, y ofrecerles los esquemas de vigilancia y eventuales tratamientos profilacticos correspondientes a su enfermedad. Para el manejo integral de estas familias es esencial contar con un equipo multidisciplinario, para poder ofrecer consejeria genetica, estudio genetico, educacion a las familias y tratamiento respectivo en forma adecuada.

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries.

Background In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth.Methods We updated search results of a recent systematic review by searching MEDLINE and Embase from Jan 1,2016, to May 5,2017, and used expert knowledge to identify published studies reporting on local regrowth in patients with rectal cancer managed by watch and wait after clinical complete response to neoadjuvant chemoradiotherapy. We restricted studies to those that defined clinical complete response using criteria equivalent to Sao Paulo benchmarks (ie, absence of residual ulceration, stenosis, or mass within the rectum on clinical and endoscopic examination). The primary outcome was 2-year cumulative incidence of local regrowth, estimated with a two-stage random-effects individual participant data meta-analysis. We assessed the effects of clinical and treatment factors using Cox frailty models, expressed as hazard ratios (HRs). From these models, we derived percentage differences in mean 0 as an approximation of the effect of measured covariates on between-centre heterogeneity. This study is registered with PROSPERO, number CRD42017070934.Findings We obtained individual participant data from 11 studies, including 602 patients enrolled between March 11,1990, and Feb 13, 2017, with a median follow-up of 37.6 months (IQR 25.0-58.7). Ten of the 11 datasets were judged to be at low risk of bias. 2-year cumulative incidence of local regrowth was 21.4% (random-effects 95% CI 15.3-27.6), with high levels of between-study heterogeneity (I 2 =61%). We noted wide between-centre variation in patient, tumour, and treatment characteristics. We found some evidence that increasing cT stage was associated with increased risk of local regrowth (random-effects HR per cT stage 1.40, 95% CI 1.00-1.94; P-trend=0. 048). In a subgroup of 459 patients managed after 2008 (when pretreatment staging by MRI became standard), 2-year cumulative incidence of local regrowth was 19% (95% CI 13-28) for stage cT1 and cT2 tumours, 31% (26-37) for cT3, and 37% (21-60) for cT4 (random-effects HR per cT stage 1.50, random-effects 95% CI 1.03-247; P-trend=0. 0330). We estimated that measured factors contributed 4.8-45-3% of observed between-centre heterogeneity.Interpretation In patients with rectal cancer and clinical complete response after chemoradiotherapy managed by watch and wait, we found some evidence that increasing cT stage predicts for local regrowth. These data will inform clinician-patient decision making in this setting. Research is needed to determine other predictors of a sustained clinical complete response. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Resumen Introduccion El estandar de tratamiento del cancer de recto localmente avanzado es la escision total del mesorrecto. Sin embargo, la preservacion del organo ha sido propuesta para los tumores con buena respuesta al tratamiento neoadyuvante. El objetivo de este estudio es investigar los resultados oncologicos de esta estrategia. Metodos Se realizo un estudio de cohorte retrospectivo, en el que se analizo a los pacientes con adenocarcinoma de recto tratados con intencion curativa entre 2005 y 2014 que, despues de recibir quimiorradioterapia neoadyuvante, presentaron una respuesta clinica completa o casi completa y fueron tratados con preservacion del recto. Resultados Durante el periodo de estudio, 204 pacientes con cancer del recto recibieron neoadyuvancia. Treinta (14,7%) presentaron una respuesta clinica completa o casi completa y se trataron segun una estrategia de preservacion de organo (23 watch & wait y 7 resecciones locales). La mediana de seguimiento fue de 46 meses (rango intercuartil: 30-68). En el grupo de watch & wait , 4 casos presentaron recurrencia local antes del ano (tasa actuarial 18,5%). Todos pudieron ser rescatados (2 con cirugia radical y 2 con resecciones locales) sin presentar nuevas recurrencias. El indice de supervivencia libre de enfermedad a distancia a 3 anos fue de 94,1% (IC 95%: 82,9-100). De los 7 casos que se trataron mediante reseccion local, ninguno presento recurrencia local. Considerando toda la muestra, la proporcion de conservacion de organo fue del 93%. Conclusiones La estrategia de preservacion de organo en el cancer rectal localmente avanzado es factible en casos con buena respuesta a la neoadyuvancia. Implementada en un grupo altamente seleccionado de pacientes, se asocia con resultados oncologicos satisfactorios.

El objetivo de este trabajo fue caracterizar demográfica y molecularmente las familias con diagnóstico de síndrome de Lynch en base a estudios genéticos. Se utilizó la base prospectiva del Registro de Epidemiología Molecular de Cáncer Colorrectal (REM-CCR) del Hospital Italiano de Buenos Aires (Clinical trials.gov NCT02781337). El criterio de inclusión fue que tuvieran hecho un estudio genético entre 1996 y 2017 (secuenciación y/o determinación de grandes rearreglos de al menos un gen reparador de error de apareamiento). Se analizaron 50 familias con los criterios de Amsterdam. En 23 (46%) se identificaron variantes patogénicas (n=19) y probablemente patogénicas (n=2). El 28.6% de las variantes patogénicas fueron originalmente descritas en esta serie, entre ellas la variante c.1911del en el exón 12 de MSH2 identificada en una familia con agregación de cáncer de mama. Fue identificada una mutación fundadora de Piamonte, Italia (c.2252_2253del). Los genes afectados incluyeron MSH2 (13 variantes)MLH1 (9 variantes) y PMS2 (1 variante). La tasa de detección de mutaciones fue del 46%. Entre las familias con mutación identificada (n=23), se detectó una edad mediana de inicio del cáncer menor (46 vs. 50 años, p=0.02) y mayor incidencia de tumores extra-colorrectales (90.5% vs. 45.8%, p

The surgical residency system ensures supervised practices to progressively move from simple to complex surgical procedures. However, ethical dilemmas could arise if patient outcome is negatively affected by this learning methodology. The objective of this study was to evaluate whether the supervised participation of residents acting as operating surgeons influences the postoperative complication rate.Surgeries performed between June 2010 and May 2011 were analyzed. The Dindo-Clavien classification was used to stratify the severity of complications. The complication rates of patients operated by supervised residents (SR) and trained surgeons (TS) were compared considering potential confounders related to the patient and surgical procedure.A total of 3697 consecutive surgical procedures were included. Age, gender, and American Society of Anesthesiologists (ASA) risk were not different between patients of both groups. The overall complication rate was 10.8 %, without significant differences between the SR and TS groups (9.8 vs. 11.4 %; P = 0.14). The severity of complications was similar in both groups. Multivariate analysis adjusted for confounders confirmed that resident participation was not an independent risk factor for complications (odds ratio 1.52; 95 % CI 0.79-2.92; P = 0.20).Supervised resident participation, as operating surgeon, does not negatively impact postoperative patient outcome. Residency training may therefore be considered as an ethical and safe learning methodology whenever implemented in the framework of an academic teaching hospital.

Background: Genetic 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. Methods: Eleven 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. Results: We 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. Conclusion: The 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., Radium Hospital Foundation (Oslo, Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, Helse Sør-Øst (Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, the French Association Recherche contre le Cancer (ARC) in the analysis, and interpretation of data, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (Gefluc) in the analysis, and interpretation of data, the Association Nationale de la Recherche et de la Technologie (ANRT, CIFRE PhD fellowship to H.T.) in the analysis, and interpretation of data and by the OpenHealth Institute in the analysis, and interpretation of data. Barretos Cancer Hospital received financial support by FINEP-CT-INFRA (02/2010), info:eu-repo/semantics/publishedVersion

To compare the intraoperative and postoperative outcomes between right laparoscopic colectomy (RLC) and left laparoscopic colectomy (LLC) for colon cancer. Patients who underwent elective RLC or LLC for colon cancer between January 2004 and December 2014 were identified and elected for a retrospective analysis. Primary outcomes were technical difficulty (including operative time, intraoperative complications, and conversion rate) and postoperative outcome (including postoperative complications, length of hospital stay, reinterventions, readmissions, and mortality). A total of 547 patients (mean age: 68.5 years old; 48.4% males) were analyzed. The RLC group had a higher mean age (71 vs 65; p

2628 Background: We investigated whether an adaptation to rectal biopsies of the recently validated consensus Immunoscore, could predict the response to neoadjuvant treatment and delineate clinical responders that could benefit from a “Watch and Wait” (W&W) strategy with acceptable outcomes. Methods: Initial biopsies from 273 patients with locally advanced rectal cancer (LARC) treated by neoadjuvant chemoradiotherapy (nCRT) followed by Total Mesorectal Excision (TME), were immunostained for CD3+ and cytotoxic CD8+ T cells and quantified by digital pathology to determine the Immunoscore within pre-treatment Biopsy (ISB). Expression level of 44 immune related genes post-neoadjuvant treatment was investigated by Nanostring technology (n = 64 patients). Results were correlated with response to neoadjuvant treatment, disease free survival (DFS) and time to recurrence (TTR). Prognostic performance of ISB was finally assessed in 73 LARC treated by W&W strategy. Results: ISB Low, Intermediate and High were respectively observed in 23.3, 50.4 and 26.3 % of the cohort. ISB was positively and significantly correlated with the response to nCRT, as evaluated by Dworak classification (P = .0034), ypTNM (P = .0003), down-staging (P = .0014), and neoadjuvant rectal (NAR) score, (P < .0001). ISB status was also positively associated with the degree of local immune activation post-neoadjuvant treatment. ISB High patients were at low risk of relapse, with 5-year DFS rates of 81.1 % (CI, 71.3-92.1 %) as compared to 57.8 % (CI, 45.9-72.9 %) in ISB low patients. In multivariate analysis, ISB was the only significant parameter at presentation associated with DFS (High vs Low: P = .001). Among W&W patients, significant difference was observed for TTR according to ISB status (High vs Low: P = .025). Conclusions: ISB could provide a reliable estimate of the response to nCRT and risk of recurrence in LARC patients' treated by TME or W&W strategy.

Background The present study aims to examine the feasibility and safety of a two-day hospital stay after laparoscopic colorectal resection (LCR) under an enhanced recovery after surgery (ERAS) pathway. Methods Between 2003 and 2010, 882 consecutive patients undergoing LCR were analyzed. Patients were grouped and analyzed according to whether their hospital stay was 2 days (group A) or longer (group B). Demographic, surgical, and postoperative data were compared. To identify independent predictive factors related to a short hospital stay, a multivariate analysis was also performed. Results Group A represented 10.3 % of this series (91 patients). There were no differences regarding age, gender, BMI, ASA, and previous abdominal surgeries between groups. Group A had a lower incidence of rectal cancer and anterior resections than group B (6.6 vs. 17.7 % [p = 0.006] and 14.3 vs. 23.4 % [p = 0.048]), respectively, and a lower mean operative time (170 min vs. 192 min; p = 0.002). Group A had a lower overall morbidity rate than group B (5.5 vs. 16.9 %; p = 0.004) and a lower incidence of surgery-related complications (5.5 vs. 14.9 %; p = 0.001). The overall conversion rate was 10 % (only one patient in group A required conversion), and the difference in conversion rate between groups was statistically significant (1.2 vs. 10.7 %; p = 0.003). Group A had a lower readmission rate (0 vs. 4.9 %; p = 0.089). Multivariate analysis showed that conversion, postoperative morbidity, and rectal prolapse were independently associated with the length of hospital stay. Conclusions A two-day hospital stay after LCR is safe and feasible under an ERAS pathway, without compromising the readmission or complication rate.

Iliopsoas abscess remains a rare condition. Together with a decreasing incidence of tuberculosis infection, pyogenic iliopsoas abscess (PIPA) has become relatively more frequent and represents more than half of iliopsoas abscesses.To analyze presentation, treatment, and outcomes in a series of patients with diagnosis of PIPA.Retrospective.A single tertiary care institution.A series of 34 consecutive patients with diagnosis of PIPA treated between 2001 and 2010 at the Hospital Italiano de Buenos Aires.Analyzed variables were: age, sex, diagnostic modality, clinical presentation, and treatment outcomes.Primary and secondary abscess occurred in 20.6% and 79.4%, respectively. The leading cause of PIPA was spondylodiscitis (38%) and computed tomography was the preferred diagnostic modality (87%). Most common presentation was left unilateral abscess in 66% of patients and most frequent isolated bacteria were Staphylococcus aureus. Fifteen patients (44%) received antibiotics as initial treatment with an initial failure rate of 80%; 11 of 15 patients required a second treatment. Sixteen patients (47%) underwent percutaneous drainage (PD) as first line treatment with a success rate of 50%. However, success rate of PD, increased to 100% after 2 drainages. Three patients were surgically drained without success (0 of 3 patients). Compared with the rest of the population, PD showed a lower hospital stay (25 vs. 14 d, respectively, P = 0.08) whereas surgery had a higher mortality rate (8% vs. 22%, respectively, P = 0.03).A single institutional retrospective study.Our series showed a higher proportion of unilateral and secondary abscess. Spondylodiscitis was the first cause of PIPA. PD seems to be the best treatment option for PIPA and compared with surgery it is associated with a higher success rate and lower hospital stay and mortality rate.

The MSH2 c.388_389del mutation has occasionally been described in Lynch families worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have identified 16 seemingly unrelated families with this germline mutation. To evaluate if this alteration is a founder or a recurrent mutation we performed haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as in four index cases and 13 relatives reported from Germany, Scotland, England, and Argentina. In the Portuguese families we observed a shared haplotype of approximately 10 Mb and all were originated from the north of Portugal. These results suggest that this alteration is a founder mutation in Portugal with a relatively recent origin. In the reported families outside Portugal with this mutation different haplotype backgrounds were observed, supporting the hypothesis that it occurred de novo on multiple occasions. We also conclude that the high proportion of families with the MSH2 c.388_389del mutation indicates that screening for this alteration as a first step may be cost-effective in the genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the north of Portugal.

Heredity is a major risk factor for colorectal cancer (CRC). Identification of individuals and families at increased risk allows for targeted surveillance, which has been shown to reduce morbidity and mortality from CRC (1, 2). Lynch syndrome is a multi-tumor syndrome with particularly high risks for colorectal, endometrial, and ovarian cancer (3–6). The syndrome is caused by germline DNA-mismatch repair (MMR) gene mutations with major contributions from MLH1 (MIM#120436) (42%), MSH2 (MIM#609309) (33%), MSH6 (MIM#600678) (18%), and PMS2 (MIM#600259) (8%). Only about one-third of the Lynch syndrome families fulfill the Amsterdam criteria (AC) (7–9). The cumulative incidence of any cancer at 70 years of age is 72% for MLH1 and MSH2 mutation carriers but lower in MSH6 (52%) and PMS2 (18%) mutation carriers. MSH6 and PMS2 carriers developed no cancers before 40 years of age (10). Mutation screening in a relatively large proportion of South American families with suspected Lynch syndrome has recently identified 99 disease-predisposing mutations in MLH1 and MSH2, which mutation spectrum is predominated by MLH1 (60%) and MSH2 (40%). Among the reported mutations, genetic hot-spot regions, new and potential founder mutations have been described in the South American population (11, 12). Several genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in at least 15 independent loci associated with CRC risk (odds ratio ranging from 1.10 to 1.26 per risk allele) (13–15). Although there is no evidence that these SNPs associated with CRC in the general population are modifiers of the risk for MMR gene mutation carriers overall and therefore any evidence of proven clinical utility in Lynch syndrome (16). The MLH1 Ile219Val (rs1799977) is a common germline alteration, located in exon 8 at the nucleotide 655. This polymorphism has been described in a high frequency of the South American Lynch syndrome population, but no modifier effect of CRC risk and MMR disease-predisposing mutation carriers was observed (17). However, it has been reported to confer a twofold-increased risk of CRC development in sporadic Mexican patients (18). Other conditions that have been associated with this polymorphism include childhood acute lymphoblastic leukemia, breast cancer, radiation-induced rectal or bladder toxicity, and ulcerative colitis (19–23). It is unknown whether the MLH1 Ile219Val polymorphism has an effect on cancer risk and in the MMR capacity in Argentinean families with suspected Lynch syndrome. Thus, we aim to determine its frequency, its correlation with disease-predisposing MMR gene mutations, and to delineate the clinical characteristics from these families.

BACKGROUND Body surface area is a measurement of body size used in clinical settings. Its impact on laparoscopic colorectal surgery has not been previously studied. OBJECTIVE The aim of this study was to assess the impact of body surface area on the conversion rate and laparoscopic operative time. DESIGN This study was conducted as a retrospective analysis of prospectively collected data. SETTING This study was conducted at a single tertiary care institution. PATIENTS Nine hundred sixteen consecutive patients operated on between January 2004 and August 2011 were identified from a prospective database. MAIN OUTCOME MEASURES Conversion rate and laparoscopic operative time were analyzed related to age, sex, obesity, disease location (colon vs rectum), type of disease (neoplastic vs nonneoplastic), history of previous surgery, and body surface area; body surface area was calculated by the Mosteller formula. Body surface area was analyzed by the use of median and quartile cutoff values (1.6, 1.8, and 2.0). Multivariate models were adjusted for different confounders. Interaction between body surface area and BMI was ruled out. RESULTS The conversion rate was 10%. Conversion rates for quartiles 1, 2, 3, and 4 were 4.4%, 8.3%, 12.7%, and 14.8%, p = 0.001. Patients with body surface area ≥ 1.8 had a higher conversion rate than those with body surface area