Analysis of long-term oncological results of clinical versus pathological responses after neoadjuvant treatment in locally advanced rectal cancer.

BACKGROUND: Nonoperative management after neoadjuvant treatment in low rectal cancer enables organ preservation and avoids surgical morbidity. Our aim is to compare oncological outcomes in patients with clinical complete response in watch and wait strategy with those who received neoadjuvant therapy followed by surgery with a pathological complete response. METHODS: Patients with non-metastatic rectal cancer after neoadjuvant treatment with clinical complete response in watch and wait approach (group 1, n = 26) and complete pathological responders (ypT0N0) after chemoradiotherapy and surgery (group 2, n = 22), between January 2011 and October 2018, were included retrospectively, and all of them evaluated and followed in a multidisciplinary team. A comparative analysis of local and distant recurrence rates and disease-free and overall survival between both groups was carried out. Statistical analysis was performed using log-rank test, Cox proportional hazards regression model, and Kaplan-Meier curves. RESULTS: No differences were found between patient's demographic characteristics in both groups. Group 1: distance from the anal verge mean 5 cm (r = 1-12), 10 (38%) stage III, and 7 (27%) circumferential resection margin involved. The median follow-up of 47 months (r = 6, a 108). Group 2: distance from the anal verge mean 7 cm (r = 2-12), 16 (72%) stage III, and 13 (59%) circumferential resection margin involved. The median follow-up 49.5 months (r = 3, a 112). Local recurrence: 2 patients in group 1 (8.3%) and 1 in group 2 (4.8%) (p = 0.6235). Distant recurrence: 1 patient in group 1 (3.8%) and 3 in group 2 (19.2%) (p = 0.2237). Disease-free survival: 87.9% in group 1, 80% in group 2 (p = 0.7546). Overall survival: 86% in group 1 and 85% in group 2 (p = 0.5367). CONCLUSION: Oncological results in operated patients with pathological complete response were similar to those in patients under a watch and wait strategy mediating a systematic and personalized evaluation. Surgery can safely be deferred in clinical complete responders.

TarSeqQC: Quality control on targeted sequencing experiments in R.

Targeted sequencing (TS) is growing as a screening methodology used in research and medical genetics to identify genomic alterations causing human diseases. In general, a list of possible genomic variants is derived from mapped reads through a variant calling step. This processing step is usually based on variant coverage, although it may be affected by several factors. Therefore, undercovered relevant clinical variants may not be reported, affecting pathology diagnosis or treatment. Thus, a prior quality control of the experiment is critical to determine variant detection accuracy and to avoid erroneous medical conclusions. There are several quality control tools, but they are focused on issues related to whole-genome sequencing. However, in TS, quality control should assess experiment, gene, and genomic region performances based on achieved coverages. Here, we propose TarSeqQC R package for quality control in TS experiments. The tool is freely available at Bioconductor repository. TarSeqQC was used to analyze two datasets; low-performance primer pools and features were detected, enhancing the quality of experiment results. Read count profiles were also explored, showing TarSeqQC's effectiveness as an exploration tool. Our proposal may be a valuable bioinformatic tool for routinely TS experiments in both research and medical genetics.

International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy.

PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.

Prognostic Factors of Long-Term Outcomes after Primary Chemo-Radiotherapy in Non-Metastatic Anal Squamous Cell Carcinoma: An International Bicentric Cohort.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with human papillomavirus (HPV) infection. The locally advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate the prognostic factors for ASCC after curative CRT. A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at two centers was performed. Complete response (CR), disease-free survival (DFS), and overall survival (OS) were analyzed by Kaplan-Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. The CR rate was 70% and was predictive of DFS (p < 0.0001) and OS (p < 0.0001), where non-CR cases were associated with shorter DFS (HR = 16.5, 95% CI 8.19-33.21) and OS (HR = 8.42, 95% CI 3.77-18.81) in a univariate analysis. The median follow-up was 38 months, with a 3-year DFS of 71%. The prognostic factors for DFS were cT1-T2 (p = 0.0002), N0 (p = 0.035), HIV-positive (p = 0.047), HIV-HPV coinfection (p = 0.018), and well-differentiated tumors (p = 0.037). The three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.02) and well-differentiated tumors (p = 0.003) were associated with better OS. The unsupervised analysis demonstrated a clear segregation of patients in three clusters, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.74 95% CI = 1.25-2.42, p = 0.0008) were enriched with the locally advanced disease, anal canal location, HIV-HPV coinfection, and non-CR. In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.

Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents.

Recently, biallelic germline variants of the DNA glycosylase genes MUTYH and NTHL1 were linked to polyposis susceptibility. Significant fractions remain without a molecular explanation, warranting searches for underlying causes. We used exome sequencing to investigate clinically well-defined adenomatous polyposis cases and families from Finland (N=34), Chile (N=21), and Argentina (N=12), all with known susceptibility genes excluded. Nine index cases (13%) revealed germline variants with proven or possible pathogenicity in the DNA glycosylase genes, involving NEIL1 (mono- or biallelic) in 3 cases, MUTYH (monoallelic) in 3 cases, NTHL1 (biallelic) in 1 case, and OGG1 (monoallelic) in 2 cases. NTHL1 was affected with the well-established, pathogenic c.268C>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>A, p.(Gly169Asp) variant was observed in two families. In a Finnish family, the variant occurred in trans with a truncating NEIL1 variant (c.821delT). In an Argentine family, the variant co-occurred with a genomic deletion of exons 2 - 11 of PMS2. Mutational signatures in tumor tissues complied with biological functions reported for NEIL1. Our results suggest that germline variants in DNA glycosylase genes may occur in a non-negligible proportion of unexplained colon polyposis cases and may predispose to tumor development.

A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk Human papillomavirus (HPV) infection. Despite improved outcomes in non-metastatic ASCC, definitive chemoradiotherapy constitutes the standard treatment for localized disease. Evidences for predictive and prognostic biomarkers are limited. Here, we performed a viral, immune, and mutational characterization of 79 non-metastatic ASCC patients with complete definitive chemoradiotherapy. HPV-16 was detected in 91% of positive cases in single infections (78%) or in coinfections with multiple genotypes (22%). Fifty-four percent of non-metastatic ASCC cases displayed mutations affecting cancer driver genes such as PIK3CA (21% of cases), TP53 (15%), FBXW7 (9%), and APC (6%). PD-L1 expression was detected in 57% of non-metastatic ASCC. Increased PD-L1 positive cases (67%) were detected in patients with complete response compared with non-complete response to treatment (37%) (p = 0.021). Furthermore, patients with PD-L1 positive tumors were significantly associated with better disease-free survival (DFS) and overall survival (OS) compared with patients with PD-L1 negative tumors (p = 0.006 and p = 0.002, respectively). PD-L1 expression strongly impacts CR rate and survival of non-metastatic ASCC patients after standard definitive chemoradiotherapy. PD-L1 expression could be used to stratify good versus poor responders avoiding the associated morbidity with abdominal perineal resection.

Prognostic Impact of An Integrative Landscape of Clinical, Immune, and Molecular Features in Non-Metastatic Rectal Cancer.

Rectal Cancer (RC) is a complex disease that involves highly variable treatment responses. Currently, there is a lack of reliable markers beyond TNM to deliver a personalized treatment in a cancer setting where the goal is a curative treatment. Here, we performed an integrated characterization of the predictive and prognostic role of clinical features, mismatch-repair deficiency markers, HER2, CDX2, PD-L1 expression, and CD3-CD8+ tumor-infiltrating lymphocytes (TILs) coupled with targeted DNA sequencing of 76 non-metastatic RC patients assigned to total mesorectal excision upfront (TME; n = 15) or neoadjuvant chemo-radiotherapy treatment (nCRT; n = 61) followed by TME. Eighty-two percent of RC cases displayed mutations affecting cancer driver genes such as TP53, APC, KRAS, ATM, and PIK3CA. Good response to nCRT treatment was observed in approximately 40% of the RC cases, and poor pathological tumor regression was significantly associated with worse disease-free survival (DFS, HR = 3.45; 95%CI = 1.14-10.4; p = 0.028). High neutrophils-platelets score (NPS) (OR = 10.52; 95%CI=1.34-82.6; p = 0.025) and KRAS mutated cases (OR = 5.49; 95%CI = 1.06-28.4; p = 0.042) were identified as independent predictive factors of poor response to nCRT treatment in a multivariate analysis. Furthermore, a Cox proportional-hazard model showed that the KRAS mutational status was an independent prognostic factor associated with higher risk of local recurrence (HR = 9.68; 95%CI = 1.01-93.2; p <0.05) and shorter DFS (HR = 2.55; 95%CI = 1.05-6.21; p <0.05), while high CEA serum levels were associated with poor DFS (HR = 2.63; 95%CI = 1.01-6.85; p <0.05). Integrated clinical and molecular-based unsupervised analysis allowed us to identify two RC prognostic groups (cluster 1 and cluster 2) associated with disease-specific OS (HR = 20.64; 95%CI = 2.63-162.2; p <0.0001), metastasis-free survival (HR = 3.67; 95%CI = 1.22-11; p = 0.012), local recurrence-free survival (HR = 3.34; 95%CI = 0.96-11.6; p = 0.043) and worse DFS (HR = 2.68; 95%CI = 1.18-6.06; p = 0.012). The worst prognosis cluster 2 was enriched by stage III high-risk clinical tumors, poor responders to nCRT, with low TILs density and high frequency of KRAS and TP53 mutated cases compared with the best prognosis cluster 1 (p <0.05). Overall, this study provides a comprehensive and integrated characterization of non-metastatic RC cases as a new insight to deliver a personalized therapeutic approach.

Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer.

Locally advanced rectal cancer (LARC) remains a medical challenge. Reliable biomarkers to predict which patients will significantly respond to neoadjuvant chemoradiotherapy (nCRT) have not been identified. We evaluated baseline genomic and transcriptomic features to detect differences that may help predict response to nCRT. Eligible LARC patients received nCRT (3D-LCRT 50.4 Gy plus capecitabine 825 mg/m2/bid), preceded by three cycles of CAPOX in high systemic-relapse risk tumors, and subsequent surgery. Frozen tumor biopsies at diagnosis were sequenced using a colorectal cancer panel. Transcriptomic data was used for pathway and cell deconvolution inferential algorithms, coupled with immunohistochemical validation. Clinical and molecular data were analyzed according to nCRT outcome. Pathways related to DNA repair and proliferation (p < 0.005), and co-occurrence of RAS and TP53 mutations (p = 0.001) were associated with poor response. Enrichment of expression signatures related to enhanced immune response, particularly B cells and interferon signaling (p < 0.005), was detected in good responders. Immunohistochemical analysis of CD20+ cells validated the association of good response with B cell infiltration (p = 0.047). Findings indicate that the presence of B cells is associated with successful tumor regression following nCRT in LARC. The prevalence of simultaneous RAS and TP53 mutations along with a proficient DNA repair system that may counteract chemoradio-induced DNA damage was associated with poor response.

[Prospective, double-blind study of topical phenylephrine treatment for nocturnal fecal incontinence in patients after ileoanal pouch construction]. / Estudio prospectivo y doble ciego del tratamiento local con fenilefrina de la incontinencia anal nocturna en pacientes con reservorio ileal.

PATIENTS: Fecal incontinence has been reported in 5.5% to 45% of patients after ileoanal pouch construction, predominantly at night. It has been shown that alpha1-adrenergic agonists as phenylephrine increase anal sphincter pressure in healthy volunteers and in patients with idiopathic fecal incontinence. The median duration of action of topical phenylephrine is seven hours. Carapeti et al have demonstrated its usefulness in patients after ileoanal pouch construction. OBJECTIVE: To demonstrate that the administration of a single dose of topical 10% phenylephrine at night is effective for the treatment of nocturnal anal incontinence in this group of patients. PATIENTS AND METHODS: We randomized 12 patients in two groups. Group A (control) received a placebo cream and group B received a 10% phenylephrine cream. The study was prospective, randomized and double-blind. RESULTS: There were no significant differences between the two groups in age, follow-up time since the closure of ileostomy and pre-treatment and intra-treatment leaks. Control group had 7 episodes of incontinence pre-treatment and 9 intra-treatment. Treated group had 3 and 5.4, respectively. (p = NS) No patient had side effects. CONCLUSIONS: Given the small number of patients included, we can not yet rule out that topical 10% phenylephrine is useful for the treatment of nocturnal fecal incontinence in patients after ileoanal pouch construction. It would be necessary to continue with studies, increasing the number of patients treated with this drug, in order to have a better evidence of its clinical utility.

[Long term functional outcomes after ileoanal pouch in patients with and without postoperative complications]. / Resultados funcionales a largo plazo luego de la coloproctectomía con reservorio ileal en pacientes con y sin complicaciones postoperatorias.

BACKGROUND: the proctocolectomy with ilealpouch (IP) has become the gold standard for surgical treatment for ulcerative colitis (UC). The postoperative complications are frequent but the definitive outcome is acceptable. AIM: our aim was to evaluate the long term functional outcome in a series of consecutive patients with IP and to establish its relation with postoperative complications. PATIENTS AND METHODS: we included 144 patients categorized in two groups: I--patients without postoperative complications (n: 71); II--patients with postoperative complications (n: 73). Patients were followed for a median time of 3.8 years (range 1-15). We evaluated: stool frequency, anal discrimination between gas and stool, voluntary evacuation inhibition, requirement of antidiarrheal medications and presence of incontinence. RESULTS: the functional outcome was similar between the two groups in terms of stool fequency medication use, anal discrimination and the voluntary inhibition of evacuation for more than 5 hours. A trend to present seepage was seen in patients with complications (34%) more than in those without them (20%; p<0.08 NS). Compared with group II, seepage in group I was significantly related with dietary lapses (p<0.01). The most frequent complication in incontinent patients was pelvic sepsis (56%). CONCLUSIONS: our study showed that most of long-term functional parameters are not influenced by the presence of postoperative complications. However, a trend for incontinence seems to be related to postoperative complications, more frequently with pelvic sepsis.

Non-surgical management of rectal cancer. Series of 68 cases, long follow up in two leading centres in Argentina.

BACKGROUND: The non-surgical management in a selected group of rectal cancer patients has shown promising results with adequate follow up. AIMS: describing the results of the non-surgical management in patients with complete clinical response, with a close follow up. METHODS: Between 2006 and 2015, patients with rectal cancer, stages I-III, without metastasis, treated with neoadjuvant CRT/CT, who had clinical complete response were included. CCR was defined through digital palpation, endoscopy-based criteria and MRI. Follow up was set according to institutional guidelines. RESULTS: 68 patients were included. Initial stage was assessed with MRI in 55/68 pts and EUS 11/68. Considering the recurrence risk factors 57.6% (29/68) were T2-3ab N0, 3.3% (2/68) were T4N0, 29% (20/68) were T3-4 N1-2, with 39.7% with positive MRC. Mean distance to the anal margin was 3cm. Chemoradiation included radiotherapy at 50.4cGy, and concurrent capecitabine. In 22% a fluoropirimidine and oxaliplatin-based schema was used as induction therapy. Median follow up was 37.5 months and response assessment time 9 weeks (5-19). Eleven patients recurred, 6 endoluminally, 3 developed mesorectal recurrence, and two distant failure. Five years DFS and OS were 76.3% and 93.8%. CONCLUSIONS: conservative management was feasible with close follow up in leading cancer centres. In this series, DFS and OS were comparable to the data already reported in the literature.

El médico a la hora de informar / The physician at the time to informing

La relación médico-paciente-familia es una interacción de gran importancia en los últimos momentos de la vida. El rol que desarrolla el médico a la hora de informar y acompañar en las situaciones límites es un aspecto de la práctica médica de fundamental importancia teniendo en cuenta que una comunicación efectiva es la base del manejo de muchos problemas emocionales y el comienzo del alivio de los síntomas fisicos. La importancia de comunicar bien radica en reducir la incertidumbre y brindar al paciente y su familia una dirección hacia dónde encaminarse.

The interaction physician-patient-family is of the greatest importance when a patient is on the verge of his death. A physician's role when he has to inform and accompany both his patient and his patient's familly in those hard limit situations is of greatest importance to the medical practice because an effective communication is the cornerstone of coping with many emotional problems and the first step to the relief of physical symptoms as well. The key to a successful communication relies in reducing the amount of uncertainty and in guiding them towards the right direction.

Poliposis serrata (antiguamente denominada poliposis hiperplásica). Presentación de un caso y revisión de la literatura / Serrated polyposis (previously named hyperplastic polyposis): case report and literature review

Antecedentes: la poliposis hiperplásica es una enfermedad esporádica, con bases genéticas poco conocidas, que se manifiesta usualmente alrededor de los 50 años de edad. Posee un riesgo aumentado para el cáncer colorrectal, el cual ha sido citado de hasta un 50 % en diferentes series de la literatura. En su patogénesis ha sido implicada la secuencia pólipo hiperplásico-adenoma serrato-cáncer colorrectal. Objetivo: presentar un caso clínico y realizar una revisión bibliográfica del tema, especialmente en relación con su pesquisa y manejo. Lugar de realización: Institución pública. Población: un paciente de 54 años de edad evaluado y tratado por cáncer de recto y poliposis hiperplásica. Método: presentación de un caso y análisis bibliográfico. Conclusiones: la poliposis hiperplásica es una enfermedad fenotípicamente heterogénica y los individuos afectados tienen riesgo aumentado para desarrollar un cáncer colorrectal.

Background: Hyperplastic polyposis is a sporadic disease, with little known genetic basis that usually present at around 50 years old. It has an increased risk of colorectal cancer up to 50%, according to different series of the literature. With regard to the pathogenesis a sequence of hyperplastic polyposis­serrated adenoma-colorectal cancer has been involved. Objective: To report on a case and to make a literature review on this subject, especially with relation to the screening and management. Place of application: Public Institution. Population: 54 years old patient evaluated and treated for rectal cancer and hyperplastic polyposis. Method: case report and literature review. Conclusions: hyperplastic polyposis is a phenotypicaly heterogeneous disease and affected individuals are at increased risk for colorectal cancer.

Resultados funcionales a largo plazo luego de la coloproctectomía con reservorio ileal en pacientes con y sin complicaciones postoperatorias / Long term functional outcomes after ileoanal pouch in patients with and without postoperative complications

Introducción: La coloproctectomía con reservorio ileal es la opción quirúrgica de elección en pacientes con colitis ulcerosa (CU). Las complicaciones postoperatorias on frecuentes pero los resultados definitivos son considerados, en general, buenos. Objetivo: nuestro objetivo fue evaluar los resultados funcionales a largo plazo de una serie consecutiva de pacientes con pouch ileal (PI) y establecer su relación con las complicaciones postoperatorias. Pacientes y métodos: incluimos 144 pacientes categorizados en 2 grupos: I- pacientes sin complicaciones postoperatorias (n: 71); y II- pacientes con complicaciones postoperatorias (n: 73). Los pacientes fueron seguidos por un tiempo medio de 3,8 años (rango 1-15 años). Evaluamos: número de deposiciones, capacidad de discriminación entre gases y materiafecal, inhibición voluntaria de la defecación, requerimiento de medicación antidiarreica y grado de incontinencia. Resultados: los resultados funcionales fueron similares entre los dos grupos con respecto al número de deposiciones, a la necesidad de tomar antidiarreicos, a la discriminación anal y a la inhibición voluntaria de la defecación por más de 5 hs. Se observó una mayor tendencia a presentar escapes en los pacientes con complicaciones (34%) respecto de aquellos sin ellas (20%; p<0.08 NS). Comparado con el grupo II, los escapes en el grupo I estaban significativamente relacionados con el incumplimiento de la dieta (p<0.01). La infección pélvica fue la complicación más frecuente en los pacientes con incontinencia (56%). Conclusiones: nuestro estudio demostró que la mayoría de los parámetros funcionales a largo plazo no son influenciados por la ocurrencia de complicaciones postoperatorias, con excepción de una tendencia a la incontinencia, más frecuentemente asociada con la infección pélvica.

Background: the proctocolectomy with ileal pouch (IP) has become the gold standard for surgical treatment for ulcerative colitis (UC). The postoperative complications are frequent but the definitive outcome is acceptable. Aim: our aim was to evaluate the long term functional outcome in a series of consecutive patients with IP and o establish its relation with postoperative complications. Patients and methods: we included 144 patients categorized in two groups: I- patients without postoperative complications (n: 71); II- patients with postoperative complications (n: 73). Patients were followed for a median time of 3.8 years (range 1-15). We evaluated: stool frequency, anal discrimination between gas and stool, voluntary evacuation inhibition, requirement of antidiarrheal medications and presence of incontinence. Results: the functional outcome was similar between the two groups in terms of stool frequency, medication use, anal discrimination and the voluntary inhibition of evacuation for more than 5 hours. A trend to present seepage was seen in patients with complications (34%) more than in those without them (20%; p<0.08 NS). Compared with group II, seepage in group I was significantly related with dietary lapses (p<0.01). The most frequent complication in incontinent patients was pelvic sepsis (56%). Conclusions: our study showed that most of long-term functional parameters are not influenced by the presence of postoperative complications. However, a trend for incontinence seems to be related to postoperative complications, more frequently with pelvic sepsis.

Prevención del cáncer colorrectal: impacto de la implementación de un registro de poliposis familiar / Colorectal cancer screening: impact of a poliposis register

Antecedentes: La PAF es una enfermedad hereditaria caracterizada por la presencia de cientos de pólipos adenomatosos colorrectales con un riesgo cercano al 100% de cáncer. El establecimiento de Registros organizados ha demostrado ser de utilidad tanto en la prevención como en la detección precoz de CCR en este grupo. Objetivos: Evaluar el impacto de la citación sistemática en la disminución de la incidencia de CCR en individuos con riesgo para PAF. Comparar el estadio tumoral al momento del diagnóstico, la edad y la sobrevida a los 5 y 10 años entre individuos citados (IC) y de consulta espontánea (CE). Pacientes y métodos: Análisis retrospectivo de la base de datos del Registro de Poliposis del Hospital Dr. Carlos Bonorino Udaondo, constituido en 1995. Dividiendo a la población en dos grupos G1: desde 1975 a 1995 y G2: desde 1995 al 2010. Análisis del número de pacientes con cáncer al momento del diagnostico en los IC y CE en ambos periodos. En aquellos que presentaban adenocarcinoma se analizo la edad de aparición, el estadio tumoral y la sobrevida a los 5 y 10 años. Resultados: Hasta 1995 habia registrados 137 pacientes con PAF; IC 45 de ellos 20% (9) presentaban cáncer al momento del diagnóstico y de los CE el 57%. Desde 1995 a la fecha hay 1804 individuos registrados, 458 con PAF (308 familias). IC 418 detectándose PAF con CCR en 11 (2.6%) y 211 fueron CE encontrando PAF con CCR en 99 (46,9%). En el grupo de IC con CCR el 75% de ellos presentaban estadios tumorales tempranas (El 58.3%, EII 6.7%), en los CE solo el 57,8% fueron estadios tempranas. Conclusiones: Desde que se estableció el Registro y se efectuó una citación sistemática de familiares, la frecuencia de CCR ha disminuido considerablemente entre IC (2.8% vs 20%) con diferencias estadísticamente significativas. El Registro además permitió efectuar un diagnostico precoz de enfermedad en los IC con una disminución de los porcentaje de estadios tardios.

Background: Familial adenomatons polyposis (FAP) is an autosomal dominant inherited disease characterized by hundreds of adenomatous polyps in the large intestine. Nearly 100% affected untreated will have colorectal cancer. The establishment of a Poliposis Registry has demonstrated decrease considerably CCR in FAP. Objetives: The aim of the present study was to evaluate changes in the incidence all CRC, before and after the establishment of the registry. Evaluate tumoral staging, aged and survival rate at 5 and 10 years in call-up patient (CP) and probans (P) with CCR. Patients and methods: A retrospective analysis of Hospital Udaondo Registry database was done. The Registry was established in 1995. The patíents were divided in two groups. G1: since 1975 until 1995 and G2 between 1995 and 2010. Results: At 1995 The Hospital Udaondo Registry included 137 patients with FAP; CP 45 - 9 with CCR (20%) and P with CCR 57% at the diagnosis moment. Since 1995 until 2010 has been included 1804 persons, 458 with FAP. Call-up Patients 418. 11 with PAF and CCR (2.8%) and 211 probans. 99 with CCR (46.9%). 75% of the CP with CCR had early stage (El 58.3%. EII 16.7%) while in the P only 57,8% were early stage. Conclusions: Since the establishment of the registry, the frequency of CRC has decreased considerably (2.8% vs 20%).

El médico como educador principal en el sistema de residencias de postgrado / The physician like main teacher in the postgraduate residence system

Las Residencias Médicas constituyen un sistema de educación para graduados médicos con el objetivo de capacitarlos en una determinada especialidad combinando los conocimientos en una disciplina con los valores del profesional. Muchos son los factores que influyen negativamente en el desarrollo de este modelo de enseñanza-aprendizaje, como por ejemplo problemas sociales, políticos y económicos. La idea principal de este trabajo es hacer una reflexión para mejorar el cumplimiento de la siguiente premisa: buena práctica humana, ética y científica.

Residencies are an advanced medical educational system intended for recently graduated physicians and their purpose is to provide them with the knowledge of a specific field and the ethical values of a professional worker. Many are the sociopolitical and economical factors which negatively influence in the development of this teaching-learning model. This paper is mainly concerned with reflecting on the premise of a good humane and ethical scientific practice that enables its better fulfilment.