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MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29 years (range 31-71) and 49.90 years (range 27-87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.

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Introducción: La escisión completa del mesocolon con linfadenectomía D3 (CME-D3) mejora los resultados de los pacientes operados por cáncer del colon. Reconocer adecuadamente la anatomía vascular es fundamental para evitar complicaciones. Objetivo: El objetivo primario fue determinar la prevalencia de las variaciones anatómicas de la arteria mesentérica superior (AMS) y sus ramas en relación a la vena mesentérica superior (VMS). El objetivo secundario fue evaluar la asociación entre las distintas variantes anatómicas y el sexo y la etnia de lo pacientes. Diseño: Estudio de corte transversal. Material y métodos: Se incluyeron 225 pacientes con cáncer del colon derecho diagnosticados entre enero 2017 y diciembre de 2020. Dos radiólogos independientes describieron la anatomía vascular observada en las tomografías computadas. Según la relación de las ramas de la AMS con la VMS, la población fue dividida en 2 grupos y subdividida en 6 (1a-c, 2a-c). Resultados: La arteria ileocólica fue constante, transcurriendo en el 58,7% de los casos por la cara posterior de la VMS. La arteria cólica derecha, presente en el 39,6% de los pacientes, cruzó la VMS por su cara anterior en el 95,5% de los casos. La variante de subgrupo más frecuente fue la 2a seguida por la 1a (36,4 y 24%, respectivamente). No se encontró asociación entre las variantes anatómicas y el sexo u origen étnico. Conclusión: Las variaciones anatómicas de la AMS y sus ramas son frecuentes y no presentan un patrón predominante. No hubo asociación entre las mismas y el sexo u origen étnico en nuestra cohorte. El reconocimiento preoperatorio de estas variantes mediante angiotomografía resulta útil para evitar lesiones vasculares durante la CME-D3. (AU)

Background: Complete mesocolic excision with D3 lymphadenectomy (CME-D3) improves the outcomes of patients operated on for colon cancer. Proper recognition of vascular anatomy is essential to avoid complications. Aim: Primary outcome was to determine the prevalence of anatomical variations of the superior mesenteric artery (SMA) and its branches in relation to the superior mesenteric vein (SMV). Secondary outcome was to evaluate the association between these anatomical variations and sex and ethnicity of the patients. Design: Cross-sectional study. Material and methods: Two hundred twenty-fivepatients with right colon cancer diagnosed between January 2017 and December 2020 were included. Two independent radiologists described the vascular anatomy of computed tomography scans. The population was divided into 2 groups and subdivided into 6 groups (1a-c, 2a-c), according to the relationship of the SMA and its branches with the SMV. Results: The ileocolic artery was constant, crossing the SMV posteriorly in 58.7% of the cases. The right colic artery, present in 39.6% of the patients, crossed the SMV on its anterior aspect in 95.5% of the cases. The most frequent subgroup variant was 2a followed by 1a (36.4 and 24%, respectively). No association was found between anatomical variants and gender or ethnic origin. Conclusions: The anatomical variations of the SMA and its branches are common, with no predominant pattern. There was no association between anatomical variations and gender or ethnic origin in our cohort. Preoperative evaluation of these variations by computed tomography angi-ography is useful to avoid vascular injuries during CME-D3. (AU)

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PURPOSE: Recently, treatment of Hinchey III diverticulitis by laparoscopic peritoneal lavage has been questioned. Moreover, long-term outcomes have been scarcely reported. Primary outcome was to determine the recurrence rate of diverticulitis after a successful laparoscopic peritoneal lavage in Hinchey III diverticulitis. Secondary outcomes were identification of associated risk factors for recurrence and elective sigmoidectomy rate. METHODS: A retrospective cohort study in a tertiary referral center was performed. Patients with Hinchey III diverticulitis who underwent a successful laparoscopic peritoneal lavage between June 2006 and December 2019 were eligible. Diverticulitis recurrence was analyzed according to the Kaplan-Meier and log-rank test, censoring for death, loss of follow-up, or elective sigmoid resection in the absence of recurrence. Risk factors for recurrence were identified using Cox regression analysis. RESULTS: Sixty-nine patients had a successful laparoscopic peritoneal lavage (mean age: 63 years; 53.6% women). Four patients had an elective sigmoid resection without recurrences. Recurrence rate was 42% (n = 29) after a median follow-up of 63 months. The cumulative global recurrence at 1, 3, and 5 years was 30% (95% CI, 20-43%), 37.5% (95% CI, 27-51%), and 48.9% (95% CI, 36-64%), respectively. Smoking (HR, 2.87; 95% CI, 1.22-6.5; p = 0.016) and episodes of diverticulitis prior to laparoscopic peritoneal lavage (HR, 5.2; 95% CI, 2.11-12.81; p < 0.001) were independently associated with an increased risk of recurrence. CONCLUSIONS: Diverticulitis recurrence after a successful laparoscopic peritoneal lavage is high, decreasing after the first year of follow-up. Smoking and previous episodes of acute diverticulitis independently increase the risk of new episodes of diverticulitis.

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Introduction: Hand-assisted laparoscopic colorectal surgery (HALS) is an alternative to straight laparoscopic approach (SL) that requires the use of a specific device to maintain the pneumoperitoneum. Our group has described an original double glove technique to replace it. Our purpose was to compare perioperative outcomes of patients undergoing HALS using this original technique vs SL. Methods: Retrospective review of a prospective database including patients who underwent elective laparoscopic colorectal resections between 2004 to 2020 at the Hospital Italiano, Argentina. Logistic regression analysis, propensity score matching, and inverse probability weighting were used to estimate adjusted treatment effects for perioperative outcomes. Results: HALS (n=458) and SL (n=1692) cases were demographically similar. HALS was associated with a shorter operative time (170.3 vs 206.9 minutes, p<0.001). Such difference was even more pronounced in obese (44.1 min), large patients (37.5 min), complex procedures (33.8 min) and surgeries carried out by non-trained surgeons (57,6 vs 31,6 minutes, p<0.001). Hand-assisted was associated with a lower conversion rate (5% vs 9.9%, p<0.001) with an adjusted odds ratio of 0.45 (95%CI 0.28-0.73). No difference in hospital stay, morbidity, and readmission rates was found. Conclusions: HALS with double-glove technique is comparable to SL in terms of postoperative outcomes keeping reduced operative time and conversion rates, especially in obese patients undergoing complex procedures.

Introducción: La cirugía colorrectal laparoscópica mano asistida (CLMA) es un abordaje alternativo a la laparoscopia directa (LD) que requiere de un dispositivo específico para mantener el neumoperitoneo. Nuestro grupo describió una técnica original de doble guante como alternativa a este dispositivo. El objetivo del presente trabajo fue analizar los resultados de esta técnica comparándola con la técnica de LD. Métodos: Se analizó una serie consecutiva de pacientes sometidos a cirugías colorrectales laparoscópicas entre 2004 y 2020 en el Hospital Italiano de Bs, As, Argentina. Se realizó un modelo de regresión múltiple de selección progresiva y apareamiento por puntaje de propensión para analizar los resultados perioperatorios. Resultados: Los casos de CLMA (n=458) y LD (n=1692) fueron demográficamente similares. CLMA se asoció a un menor tiempo operatorio (170,3 vs 206,9 minutos, p<0.001). Dicha reducción fue más marcada en obesos (44.1 min), pacientes grandes (37.5 min), cirugías complejas (33.8 min) y en procedimientos realizados por cirujanos no entrenados (57,6 vs 31,6 minutos, p<0.001). CLMA resultó tener menor índice de conversión (5% vs 9.9%, p<0.001) con una razón de probabilidades ajustada de 0,45. No se hallaron diferencias en cuanto a estadía hospitalaria, morbimortalidad y readmisión. Conclusión: CLMA con doble guante es comparable a la LD manteniendo un tiempo operatorio reducido y bajo índice de conversión, particularmente en pacientes obesos sometidos a procedimientos complejos.

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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.

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BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSION: Fluoroscopy-endoscopy-guided recanalization is an effective and safe treatment option for complete colorectal anastomotic stricture.

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Although the incidence is uncertain, some case reports suggest that COVID 19 infection is associated with an increased risk of venous thromboembolism. We suggest starting prophylactic anticoagulant therapy for all patients hospitalized with a symptomatic infection with COVID-19, unless contraindicated, with enoxaparin 40 mg SC daily if creatinine clearance is greater than 30 ml/min.

Si bien la incidencia es incierta, algunos reportes de caso sugieren que la infección por COVID 19 se asocia con un aumento del riesgo de tromboembolismo venoso. Sugerimos iniciar tromboprofilaxis a todos los pacientes hospitalizados por síntomas asociados con una infección por COVID-19, a menos que esté contraindicado, con enoxaparina 40 mg SC diariamente si el clearance de creatinina es mayor a 30 ml/min.

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Los contenidos de este capítulo se basan en la 3a edición de las Clínicas Quirúrgicas de Cáncer Colorrectal. C. Vaccaro y N. Peralta. del hospital ediciones 2020 (en prensa)

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Si bien la incidencia es incierta, algunos reportes de caso sugieren que la infección por COVID 19 se asocia con un aumento del riesgo de tromboembolismo venoso. Sugerimos iniciar tromboprofilaxis a todos los pacientes hospitalizados por síntomas asociados con una infección por COVID-19, a menos que esté contraindicado, con enoxaparina 40 mg SC diariamente si el clearance de creatinina es mayor a 30 ml/min.

Although the incidence is uncertain, some case reports suggest that COVID 19 infection is associated with an increased risk of venous thromboembolism. We suggest starting prophylactic anticoagulant therapy for all patients hospitalized with a symptomatic infection with COVID-19, unless contraindicated, with enoxaparin 40 mg SC daily if creatinine clearance is greater than 30 ml/min.

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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.

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Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso. (AU)

It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother's skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project "Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents". At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research. (AU)

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Venous thromboembolic disease (VTE) in hospitalized adults has high morbidity and mortality, is the origin of chronic complications and increased cost for the health system. Since the publication of recommendations for thromboprophylaxis in hospitalized patients in 2013, new alternatives and strategies have emerged, which motivated us to update our recommendations. Although there are different consensus and clinical practice guidelines, adherence to them is suboptimal. The different therapeutic alternatives for hospitalized adult patients (non-surgical, surgical non-orthopedic, with and without cancer, orthopedic an d pregnant) have been updated, paying particular attention to the drugs available in Argentina.

La enfermedad tromboembólica venosa (ETV) en adultos hospitalizados posee elevada morbimortalidad, es origen de complicaciones crónicas y determina incrementos de costos para el sistema de salud. Desde la publicación de recomendaciones de tromboprofilaxis en pacientes internados en 2013, han surgido nuevas alternativas y estrategias, que nos motivaron a actualizar nuestras recomendaciones. A pesar de que existen diferentes consensos y guías de práctica clínica la adherencia a las mismas es subóptima. Se han actualizado las diferentes alternativas terapéuticas para los adultos hospitalizados (clínicos no quirúrgicos, quirúrgicos no ortopédicos, con y sin cáncer, ortopédicos y embarazadas), poniendo particular atención en los fármacos disponibles en Argentina.

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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.

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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.

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Inactivating mutations in the MLH1 gene cause the cancer predisposition Lynch syndrome, but for small coding genetic variants it is mostly unclear if they are inactivating or not. Nine such MLH1 variants have been identified in South American colorectal cancer (CRC) patients (p.Tyr97Asp, p.His112Gln, p.Pro141Ala, p.Arg265Pro, p.Asn338Ser, p.Ile501del, p.Arg575Lys, p.Lys618del, p.Leu676Pro), and evidence of pathogenicity or neutrality was not available for the majority of these variants. We therefore performed biochemical laboratory testing of the variant proteins and compared the results to protein in silico predictions on structure and conservation. Additionally, we collected all available clinical information of the families to come to a conclusion concerning their pathogenic potential and facilitate clinical diagnosis in the affected families. We provide evidence that four of the alterations are causative for Lynch syndrome, four are likely neutral and one shows compromised activity which can currently not be classified with respect to its pathogenic potential. The work demonstrates that biochemical testing, corroborated by congruent evolutionary and structural information, can serve to reliably classify uncertain variants when other data are insufficient.

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