Pólipos adenomatosos en familiares de primer grado de pacientes con cáncer del colon

Introducción: El cáncer colorectal constituye en la actualidad la segunda neoplasia maligna más frecuente. La mayoría son esporádicos, otra pequeña proporción corresponde a formas hereditarias. Sin embargo, se estima que en un 15 % a 20 % de casos pueden existir un componente hereditario asociado. Los familiares de primer grado de pacientes con cáncer colorrectal, constituyen un universo de mayor riesgo que la población general de padecer esta enfermedad, por lo que se recomienda el cribado en estos individuos. Objetivo: Determinar la frecuencia de pólipos adenomatosos en individuos con familiares de primer grado diagnosticados con cáncer de colon. Métodos: Se realizó un estudio descriptivo, de corte transversal, que incluyó a 126 adultos con familiares de primer grado de consanguinidad con cáncer de colon, a los que se les realizó colonoscopia en el Instituto de Gastroenterología entre diciembre de 2019 y diciembre 2021. Se describen las características de los pólipos adenomatosos encontrados. Resultados: La media para la edad fue de 55,9 ± 10,6, predominaron las mujeres. Se encontraron pólipos adenomatosos; 27 eran sésiles y 12 pediculados; en 26 (66,7 %), el tamaño era menor de 10 mm. La mayoría de los pólipos, fueron del tipo tubular. Se observó diversidad en cuanto a la localización de las lesiones, sin que existiera un predominio en ningún segmento anatómico. Conclusiones: Lesiones precursoras del cáncer colorrectal, como los pólipos adenomatosos, son frecuentes en individuos asintomáticos con familiares de primer grado de consanguinidad que padecieron esta neoplasia maligna.

Introduction : Colorectal cancer is currently the second most frequent neoplasm. Most of them are sporadic, another small proportion corresponds to hereditary forms. However, it is estimated that in 15-20% of cases there may be an associated hereditary component. First-degree relatives of patients with colorectal cancer constitute a universe with a higher risk of developing this disease than that of the general population, so screening is recommended in these individuals. Objective : To determine the frequency of adenomatous polyps in individuals with first-degree relatives diagnosed with colon cancer. Methods : A descriptive, cross-sectional study was carried out, including 126 adult relatives with first-degree blood relatives with colon cancer, who underwent colonoscopy at the Institute of Gastroenterology between December 2019 and December 2021. The characteristics of the adenomatous polyps found are described. Results : The mean for age was 55.9 ± 10.6, women predominated: 94 (74.6 %). Thirty-nine (30.9 %) adenomatous polyps were found; 27 (69.2 %) were sessile and 12 (30.7 %) pedunculated; in 26 (66.7 %) the size was less than 10 mm. The majority, 37 (94.8 %), were of the tubular type. Diversity was observed as to the location of the lesions, with no predominance in any anatomical segment. Conclusions : Precursor lesions of colorectal cancer, such as adenomatous polyps, are common in asymptomatic individuals with first-degree relatives who have had this malignancy.

Caracterización clínica y epidemiológica de los pacientes con cáncer de colon / Clinical and epidemiological characterization of patients with colon cancer

INTRODUCCIÓN. El cáncer de colon es una neoplasia del tubo digestivo considerada una de las más frecuentes en ambos sexos y que predomina en adultos mayores. OBJETIVO. Describir las características clínicas y epidemiológicas de los pacientes con cáncer de colon. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, retrospectivo. Población de 1 601 y muestra de 210 datos de Historias Clínicas Electrónicas de pacientes diagnosticados con cáncer de colon, atendidos por la Unidad de Oncología del Hospital de Especialidades Carlos Andrade Marín de la ciudad de Quito en el periodo enero de 2016 a diciembre de 2019. Criterios de inclusión: diagnóstico confirmado de Cáncer de Colon, edad igual o mayor a 18 años, y disponer de todos los datos clínicos requeridos en el estudio. Se utilizó el método de muestreo probabilístico con lo que se estimó una proporción para el estudio con un intervalo de confianza del 95%, un margen de error del 5% y una frecuencia esperada del 3%, de donde se obtuvo una muestra ajustada al 10% de pérdidas. El procesamiento de datos se realizó en los programas Microsoft Excel versión 16 y el Statistical Package for Social Sciences versión 24. RESULTADOS. La mayor presentación fue en adultos mayores de 50 años, con una relación 1:1 en cuanto a sexo, y en la procedencia, se ubicó mayoritariamente en la población de la región Sierra; las personas con una actividad económica de tipo profesional fueron las más afectadas; en lo que se refiere a los antecedentes se encontró mayor relación en los personales y dentro de estos los pólipos; no hubo relación con los antecedentes quirúrgicos ni familiares. El síntoma de debut más prevalente fue el dolor abdominal; la mayoría fueron sometidos a colonoscopia; predominó la lateralidad derecha y el tipo histológico principalmente identificado fue el adenocarcinoma. CONCLUSIÓN. No se observó relación estadísticamente significante entre estadíos, evolución y tratamientos instaurados, lo que pudo estar influenciado por el muestreo al azar; y que el 53,30% de los pacientes aún se encuentra en controles.

INTRODUCTION. Colon cancer is a neoplasm of the digestive tract considered one of the most frequent in both sexes and predominantly in older adults. OBJECTIVE. To describe the clinical and epidemiological characteristics of patients with colon cancer. MATERIALS AND METHODS. Observational, descriptive, retrospective study. Population of 1 601 and sample of 210 data from Electronic Medical Records of patients diagnosed with colon cancer, attended by the Oncology Unit of the Hospital de Especialidades Carlos Andrade Marín of the city of Quito in the period January 2016 to December 2019. Inclusion criteria: confirmed diagnosis of Colon Cancer, age equal to or older than 18 years, and having all the clinical data required in the study. The probability sampling method was used with which a proportion was estimated for the study with a confidence interval of 95%, a margin of error of 5% and an expected frequency of 3%, from which a 10% loss adjusted sample was obtained. Data processing was performed in Microsoft Excel version 16 and Statistical Package for Social Sciences version 24. The greatest presentation was in adults over 50 years of age, with a 1:1 ratio in terms of sex, and in terms of origin, it was mainly located in the population of the Sierra region; people with a professional economic activity were the most affected; in terms of history, a greater relationship was found in personal history and within these, polyps; there was no relationship with surgical or family history. The most prevalent debut symptom was abdominal pain; the majority underwent colonoscopy; right laterality predominated and the histological type mainly identified was adestatistically significant relationship was observed between stages, evolution and treatment, which could be influenced by random sampling; and that 53,30% of the patients are still in controls.

Pancreatic solid-pseudopapillary neoplasm in patients with familial adenomatous polyposis / Neoplasia sólida pseudopapilífera pancreática em pacientes com polipose adenomatosa familiar

ABSTRACT BACKGROUND: Solid pseudopapillary neoplasm of the pancreas is an uncommon pancreatic tumor, which is more frequent in young adult women. Familial adenomatous polyposis is a genetic condition associated with colorectal cancer that also increases the risk of developing other tumors as well. AIM: The aim of this study was to discuss the association of familial adenomatous polyposis with solid pseudopapillary neoplasm of the pancreas, which is very rare. METHODS: We report two cases of patients with familial adenomatous polyposis who developed solid pseudopapillary neoplasm of the pancreas of the pancreas and were submitted to laparoscopic pancreatic resections with splenic preservation (one male and one female). RESULTS: ß-catenin and Wnt signaling pathways have been found to play an important role in the tumorigenesis of solid pseudopapillary neoplasm of the pancreas, and their constitutive activation due to adenomatous polyposis coli gene inactivation in familial adenomatous polyposis may explain the relationship between familial adenomatous polyposis and solid pseudopapillary neoplasm of the pancreas. CONCLUSION: Colonic resection must be prioritized, and a minimally invasive approach is preferred to minimize the risk of developing desmoid tumor. Pancreatic resection usually does not require extensive lymphadenectomy for solid pseudopapillary neoplasm of the pancreas, and splenic preservation is feasible.

RESUMO RACIONAL: A neoplasia sólida pseudopapilífera do pâncreas é um tumor pancreático incomum, mais frequente em mulheres jovens. A polipose adenomatosa familiar, por sua vez, é uma condição genética associada a câncer colorretal e que também aumenta o risco de desenvolvimento de outros tumores. OBJETIVOS: Discutir a associação entre polipose adenomatosa familiar e neoplasia sólida pseudopapilífera, que é bastante rara. MÉTODOS: Reportamos dois casos de pacientes com polipose adenomatosa familiar, um homem e uma mulher, que desenvolveram neoplasia sólida pseudopapilífera do pâncreas e foram submetidos a ressecção laparoscópica com preservação esplênica. RESULTADOS: As vias de sinalização da ß-catenina e Wnt tem um papel importante na tumorigênese da neoplasia sólida pseudopapilífera, e sua ativação constitutiva devido a inativação do gene adenomatous polyposis coli na polipose adenomatosa familiar pode explicar a relação entre polipose adenomatosa familiar e neoplasia sólida pseudopapilífera. CONCLUSÕES: A ressecção do cólon deve ser priorizada, com preferência pela abordagem minimamente invasiva para minimizar o risco de desenvolvimento de tumor desmoide. A ressecção pancreática geralmente não requer linfadenectomia extensa para neoplasia sólida pseudopapilífera, portanto, a preservação esplênica é factível.

AXIN2-associated adenomatous colorectal polyposis

Abstract: Introduction Most cases of colorectal cancer (CRC) occur sporadically; however, ~3% to 6% of all CRCs are related to inherited syndromes, such as Lynch syndrome and familial adenomatous polyposis (FAP). The adenomatous polyposis coli (APC) andmutY DNA glycosylase (MUTYH) germline mutations are the main genetic causes related to colorectal polyposis. Nevertheless, in many cases mutations in these genes have not been identified. The aim of the present case report is to describe a rare case of genetic colorectal polyposis associated with the axis inhibition protein 2 (AXIN2) gene. Case Report: The first colonoscopy screening of a 61-year-old male patient with no known family history of CRC revealed ~ 50 colorectal polyps. A histological evaluation of the resected polyps showed low-grade tubular adenomas. Germline genetic testing through a multigene panel for cancer predisposition syndromes revealed a pathogenic variant in the AXIN2 gene. In addition to colorectal polyposis, the patient had mild features of ectodermal dysplasia: hypodontia, scant body hair, and onychodystrophy. Discussion: The AXIN2 gene acts as a negative regulator of the Wnt/β -catenin signaling pathway, which participates in development processes and cellular homeostasis. Further studies are needed to support the surveillance recommendations for carriers of the AXIN2 pathogenic variant. (AU)

Research advances in the association between nonalcoholic fatty liver disease and colorectal adenomatous polyps / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) and colorectal adenomatous polyps are closely associated with the various components of metabolic syndrome. This article summarizes the recent studies on the association between NAFLD and colorectal adenomatous polyps, and the results show that NAFLD is associated with an increased risk of colorectal adenomatous polyps, while related mechanism remains unclear, which may be associated with insulin resistance, chronic inflammatory response, adipokines, and intestinal flora disturbance.

Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

The fluctuation of APC gene in WNT signaling with adenine deletion of adenomatous polyposis coli, is associated in colorectal cancer / A flutuação do gene da APC na via de sinalização WNT com deleção de adenina na polipose adenomatosa do cólon está associada ao câncer colorretal

ABSTRACT Colorectal cancer is one of the most important malignancies in the classification of gastrointestinal cancers. One of the predisposing factors at molecular level for this cancer is via WNT signaling which is associated with the vast numbers of different genes. Thus, in this study, we aimed to investigate whether Adenomatous Polyposis Coli gene (APC) mutation of rs41115in two locations such as 132.002 and 131.989 acts as a trigger or cause of colorectal cancer. Relatively, 30 blood samples of colorectal cancer patients and 30 normal blood samples as control group after colonoscopy and also confirmation of pathology report at Rohani Hospital in Babol (Iran) were investigated. The primers were designed in order to be included the rs41115 to identify the particular polymorphisms of gene. The polymerase chain reaction (PCR direct sequencing method) was used. Conclusively, deletion of adenine in two specific locations such as 131.989 and 132.002 has been identified, but there was no relationship between rs41115 polymorphisms located in adenomatous polyposis coli gene and colorectal cancer.

RESUMO O câncer colorretal é uma das neoplasias malignas mais importantes na classificação dos cânceres gastrointestinais. Um dos fatores predisponentes no âmbito molecular para esse câncer é através da via de sinalização WNT, que está associada a um grande número de genes diferentes. Portanto, neste estudo, objetivamos investigar se a mutação rs41115 do gene da polipose adenomatosa do cólon (Adenomatous Polyposis Coli - APC) em dois locais como 132.002 e 131.989 atua como gatilho ou como causa do câncer colorretal. Relativamente, 30 amostras de sangue de pacientes com câncer colorretal e 30 amostras de sangue normal (grupo controle) foram analisadas após a colonoscopia, bem como a confirmação do laudo da patologia no Rohani Hospital em Babol (Irã). Os primers foram projetados de modo a incluir o rs41115 para identificar os polimorfismos particulares do gene. A reação em cadeia da polimerase (método de sequenciamento direto por PCR) foi utilizada. Conclusivamente, a deleção de adenina em dois locais específicos, como 131.989 e 132.002, foi identificada, mas não houve relação entre o polimorfismo rs41115 localizado no gene da polipose adenomatosa do cólon e o câncer colorretal.

Comportamiento de los pólipos de colon y recto en pacientes sometidos a colonoscopia terapéutica / Behavior of colon and rectum polyps in patients undergoing therapeutic colonoscopy

RESUMEN Fundamento: el intestino grueso se extiende desde el ciego hasta el orificio del ano. La mucosa contiene en su espesor, numerosas glándulas tubulares, en ella se pueden encontrar lesiones, son los pólipos las más frecuentes. Objetivo: determinar el comportamiento de los pólipos de colon y recto en pacientes sometidos a colonoscopia terapéutica. Métodos: se realizó un estudio observacional descriptivo de corte transversal. El universo fue 179 pacientes, con diagnóstico al menos de un pólipo. La muestra no probabilística quedó formada por los 166 pacientes que cumplieron, criterios de inclusión y exclusión, de ellos se analizaron 207 pólipos. La información se extrajo de las historias clínicas, registro de procederes e informes de estudio histológico. Resultados: la edad que predominó fue entre 60-69 años, prevaleció el sexo femenino. Imperó el sangramiento digestivo bajo macroscópico como manifestación clínica . Se acentuaron las localizaciones en el hemicolon izquierdo. Las lesiones de tamaño mediano sobresalieron y las lesiones sésiles fueron las que se destacaron. Los pólipos adenomatosos constituyeron los de mayor observación. Conclusiones: predominaron el grupo de edades entre 60-69 años, del sexo femenino. El sangramiento digestivo bajo macroscópico fue la manifestación clínica más observada. Los pólipos localizados en colon sigmoides, tamaño mediano, sésiles y adenomatosos resultaron los más frecuentes.

ABSTRACT Background: the large intestine extends from the cecum to the orifice of the anus. The mucosa contains in its thickness, numerous tubular glands, in it you can find lesions, polyps are the most frequent. Objective: to determine the behavior of colon and rectum polyps in patients undergoing therapeutic colonoscopy. Methods: a cross-sectional descriptive observational study was carried out. The universe was 179 patients, with at least one polyp diagnosed. The non-probabilistic sample was formed by the 166 patients who met, inclusion and exclusion criteria, of which 207 polyps were analyzed. The information was extracted from the medical charts, record of procedures and histological study reports. Results: the age that predominated was between 60-69 years, the female sex prevailed. The digestive bleeding under macroscopic was the most frequent clinical manifestation. The locations in the left semicolon were accentuated. The lesions of medium size stood out. The sessile lesions were those that highlighted. The adenomatous polyps constituted the most observed ones. Conclusions: the group of ages between 60-69 years, of the female sex, predominated. The digestive bleeding under macroscopic was the most observed clinical manifestation. The polyps located in sigmoid colon, medium size, sessile and adenomatous were the most frequent.

Postoperative developed intra-abdominal desmoid tumor after surgical resection of gastrointestinal malignancy: A review of 10 cases

PURPOSE: Desmoid tumors are locally aggressive tumors with no known potential for metastasis. They tend to recur even after complete excision. Sometimes it is not easy to differentiate between intra-abdominal desmoid and tumor recurrence, especially after gastrointestinal (GI) tumor resection. The current study aims to review the characteristics, management, and outcomes of patients with intra-abdominal desmoid tumor post GI resection.METHODS: During the period between 2007 and 2018, after a retrospective review of patients' clinical data, 10 patients were finally included. Medical records were screened for demographic, clinical, pathological data, management strategy, postoperative morbidity, mortality, recurrence rate and follow-up.RESULTS: The study comprised 10 patients (8 males). The median age was 53.5 years (range, 35–68 years). Two patients diagnosed as familial adenomatous polyposis (FAP). All the patients underwent previous GI resection: three (30%) for colon cancer, three (30%) gastrectomy, two (20%) total proctocolectomy with ileal pouch-anal anastomosis (TPC+IPAA) for FAP, one (10%) low anterior resection (three rectal cancers) and one (10%) distal pancreatectomy. The tumor was found to be in bowel mesentery in eight cases (80%). The median tumor size was 5.3 cm (range, 2.6–19.0 cm). Six patients (60%) underwent open resection, while four patients (40%) underwent laparoscopic surgery. Complications occurred in five cases (50%) and ranged from Clavien-Dindo (II-III). The median follow-up period was 16.5 months (1.5–136.0 months) with recurrence in one case (10%). Pathology came out to be desmoid tumor fibromatosis in all cases.CONCLUSION: When a mass develops after surgical resection for abdominal GI malignancy and tends to be large in size, located in the bowel mesentery and away from previous primary tumor site, most probably it is desmoid rather than tumor recurrence.

Genetic Analysis of A Familial Adenomatous Polyposis Pedigree / 胃肠病学

Background: The adenomatous polyposis coli (APC) gene mutation is closely related to the risk of familial adenomatous polyposis (FAP). Aims: To analyze the genetic etiology of a FAP pedigree. Methods: FAP was diagnosed in a patient with repeated hematochezia after the receiving of endoscopy, pathological analysis and family history investigation. Genetic analysis was conducted by new-generation sequencing (NGS) technique in the FAP family members. Results: A heterozygous mutation of APC gene c.2800_2803delACTT (p.T934fs) was existed in the family members, which led to the frame shifts of APC gene and resulted in the change of encoding amino acids sequence and formed the abnormal proteins. This mutation could lead to serious FAP symptoms with early onset of colorectal adenoma and carcinogenesis. Conclusions: NGS can diagnose the disease much earlier and more accurately, and provide a new detection method for the early prevention of genetic diseases. The heterozygous mutation of p.T934fs is the root etiology of the clinical phenotype of this FAP pedigree, and polypectomy should be considered in affected members for preventing the carcinogenesis of colon.

Design, synthesis and structure-activity relationship study of APC/Asef inhibitors / 上海交通大学学报（医学版）

Objective: To design and synthesize APC/Asef peptide inhibitors and investigate the structure-activity relationship between peptides inhibitors and APC protein for exploring better inhibitors. Methods: Based on the best-class inhibitor we had found before-MAI-400, eleven peptide inhibitors were designed, which included the changes of N-terminal capping group, the first amino acid Ala, the fifth amino acid Leu and the last amino acid Glu. According to the results of fluorescence polarization activity detection system and molecular docking, the structure-activity relationship of peptide inhibitors was investigated. Results: Among the eleven peptides, MPI-11 had the highest affinity, whose half maximal inhibitory concentration (IC50) was 0.973 1 mmol/L. The capping group of peptide N-terminal with tert-butoxycarbonyl group reduced the activity slightly. The substitution of the Ala caused different results, changing into Trp, His and Thr definitely reduced the activity but the substitution by Tyr or Phe did not influence the activity too much. And introducing benzene ring into the side chain of Leu had few effects on activity improving. The substitution of side chain carboxyl for amide at the C-terminal glutamate had little effect on the activity. Conclusion: Among the eleven peptides, the capping group of peptide N-terminal cannot be substituted into small groups and Ala cannot be substituted into other amino acids.

Large desmoid tumors in familial adenomatous polyposis: a successful outcome

Desmoid tumors develop from connective tissue, fasciae, and aponeuroses, and may occur in the context of familial adenomatous polyposis or may arise sporadically; also, they may be extra-abdominal, intra-abdominal, or located in the abdominal wall. These benign tumors have a great aggressiveness with a high rate of local recurrence. Familial adenomatous polyposis is an inherited condition with autosomal dominant transmission, and is characterized by the development of multiple colonic and rectal adenomatous polyps, as well as desmoid tumors. We present the case of a 54-year-old woman with germline APC gene mutation, who underwent a total colectomy, subsequently developing two large infiltrative solid intra-abdominal lesions consistent with desmoid tumors. Medical treatment with Cox-2 inhibitors was initiated without result. She was submitted to resection for intestinal obstruction, but developed local recurrence. The lesions were also unresponsive to tamoxifen, and chemotherapy was initiated with dacarbazine plus doxorubicin, switching to vinorelbine plus methotrexate, achieving a good response in all lesions after 12 months. The approach to these intra-abdominal lesions should be progressive, beginning with observation, then a medical approach with non-steroidal anti-inflammatory drugs or with an anti-hormonal agent. Afterwards, if progression is still evident, chemotherapy should be started. Surgery should be reserved for resistance to medical treatment, in palliative situations, or for extra-abdominal or abdominal wall desmoids tumors.

Poliposis adenomatosa familiar: a propósito de 2 casos / Familiar Adenomatous Polyposis: Report of 2 Cases

La poliposis adenomatosa familiar (PAF) se basa en una mutación autosómica dominante de pérdida de la función en el gen supresor tumoral APC. El síndrome de Gardner es un tipo de PAF y está caracterizado por múltiples pólipos adenomatosos colónicos además de anormalidades extracolónicas como tumores desmoides, osteomas, lipomas, anormalidades dentales, quistes dermoides y adenomas duodenales. Este reporte tiene como propósito presentar dos casos referentes a PAF. El primer caso, trata de un paciente con osteomas e historia de hematoquezia, con diagnóstico de sindrome de Gardner posterior a la colonoscopia. El segundo caso es un paciente con historia familiar de cáncer de colon, que al examen colonoscópico se le diagnostica PAF con adenocarcinoma tubular bien diferenciado. Se decide reportar los casos debido a que son los primeros reportes en el Perú sobre esta entidad

Familial Adenomatous polyposis (FAP) it is based on an autosomal dominant mutation which results in loss of function of the APC tumor suppressor gene. On the other hand, Gardner syndrome is a type of FAP and is characterized for multiple colonic adenomatous polyps and extracolonic abnormalities as desmoid tumors, osteomas, lipomas, dental abnormalities, dermoid cysts and duodenal adenomas. This report aims to present two patients with FAP: The first one is a patient who presented with osteomas and hematochezia, being diagnosed with Gardner Syndrome after the colonoscopy. The second patient has a family history of colon cancer, who is diagnosed with FAP with tubular adenocarcinoma. We decide to report both cases due to the absence of previous reports in Peru

Síndrome de Gardner: relato de caso e breve revisão da literatura / Gardner Syndrome: case report and brief review of the literature

Modelo do estudo: Relato de caso. Importância do problema e comentários: A Síndrome de Gardner trata-se de uma variante da Polipose Adenomatosa Familiar (PAF), com associação de pólipos gastrointestinais, tumores de partes moles e tumores ósseos. É uma desordem rara e o diagnóstico precoce é crucial para redução da morbimortalidade. O presente estudo relata um caso de Síndrome de Gardner com seus achados clínicos e radiológicos, além de apresentar breve revisão da literatura. (AU)

Type of study: Case report. Relevance and comments: Gardner Syndrome is a variant of Familial Adenomatous Polyposis (FAP), with the association of gastrointestinal polyps, soft tissue tumors and bone tumors. It is a rare disorder and early diagnosis is crucial to reduce its morbimortality. The present report illustrates a case of Gardner Syndrome with its clinical and radiologic features, as well as a brief review of the literature. (AU)

Genetic profile, risk factors and therapeutic approach of desmoid tumors in familial adenomatous polyposis / Perfil genético, fatores de risco e abordagem terapêutica dos tumores desmóides na Polipose Adenomatosa Familiar

ABSTRACT Introduction: Desmoid tumors are the main extraintestinal manifestation of FAP, presenting high morbidity and mortality. It is a neoplasia without metastasis capacity, but with infiltrative growth and with a high rate of recurrence. In familial forms, these tumors are associated with a germinal mutation in the APC gene, with a genotype-phenotype correlation influenced by other risk factors. Materials and methods: A review of articles published since the year 2000 in Portuguese, English or Spanish on desmoid tumors in patients with FAP was carried out. A total of 49 publications were included. Results: The site of the mutation in the APC gene is related to the severity of FAP and to the frequency of desmoid tumor. Mutations located distally to codon 1309 are associated with a more attenuated polyposis, but with higher frequency of desmoid tumors. Clinically, these tumors may or may not be symptomatic, depending on their size and location. In their treatment, priority should be given to medical therapy, especially in intra-abdominal tumors, with surgery being the last option if there are no other complications. Discussion: These tumors are associated with certain risk factors: genetic (mutation site), hormonal (estrogenic environment) and physical (surgical trauma) ones. In young women, a later prophylactic colectomy is suggested. Moreover, the laparoscopic approach to prophylactic surgery seems to be an option that reduces surgical trauma and consequently the appearance of desmoid tumors. Conclusion: The step-up medical approach has been shown to be valid in the treatment of intra-abdominal desmoid tumors, and medical treatment should be the first therapeutic option.

RESUMO Introdução: Os tumores desmóides são a principal manifestação extraintestinal da PAF, apresentando elevada morbimortalidade. É uma neoplasia sem capacidade de metastização, mas com crescimento infiltrativo e com alta taxa de recorrência. Nas formas familiares associa-se a uma mutação germinativa no gene APC, havendo uma correlação genótipo-fenótipo influenciada por outros fatores de risco. Materiais e métodos: Foi efetuada uma revisão de artigos publicados desde o ano 2000, em português, inglês ou espanhol, acerca de tumores desmóides em doentes com PAF. Foram incluídas, no total, 49 publicações. Resultados: O local da mutação no gene APC relaciona-se com a gravidade da PAF e frequência de tumor desmóide. Mutações localizadas distalmente ao codão 1309 associam-se a uma polipose mais atenuada, mas a maior frequência de tumor desmóide. Clinicamente podem ser, ou não, sintomáticos, dependendo do seu tamanho e localização. No seu tratamento deve ser dada prioridade à terapêutica médica, sobretudo nos tumores intra-abdominais, colocando a cirurgia como última opção, caso não hajam outras complicações. Discussão: Estes tumores associam-se a determinados fatores de risco: genéticos (local da mutação), hormonais (ambiente estrogénico) e físicos (trauma cirúrgico). Nas mulheres jovens sugere-se a realização de colectomia profilática mais tardiamente. Além disso, a abordagem laparoscópica para a cirurgia profilática parece ser uma opção que diminui o trauma cirúrgico e consequentemente o aparecimento de tumores desmóides. Conclusão: A abordagem médica em step-up mostrou ser válida no tratamento de tumores desmóides intra-abdominais, devendo o tratamento médico ser a primeira opção terapêutica.

Research progress on role of Wnt signaling pathway in regulation of tumors / 中国药理学通报

Wnt signaling pathway is a highly conservative signal pathway controlling cell growth,differentiation,apoptosis and self-renewal.This signal pathway is often abnormally activated in tumor development and progression,which can cooperate or antagonize with other signal pathways to regulate tumor prolifera-tion,migration and invasion.This paper makes a review of the recent research of Wnt signaling pathway progression and its function in tumor growth regulation.

A Case Report of Gardner-Associated Fibroma in 19-Month-Old Girl / 소아외과

Gardner-associated fibroma (GAF) is a benign lesion of soft tissue which has recently been described and is exceedingly rare in children. GAF is associated with adenomatous polyposis coli gene mutation, familial adenomatous polyposis and desmoid. We report a case of patient with soft tissue tumor on her lower back which was turned out to be GAF. The patient was a 19-month-old female who visited out-patient clinic with palpable mass on her lower back and we performed surgical excision. The tumor was located at subcutaneous and we excised the tumor including surrounding soft tissue. She discharged without any complication on surgery day. The pathologic report showed dense collagenous tissue with spindle cell and adipose tissue, suggestive of GAF. We are planning to check gene study and to perform endoscopy and abdominal ultrasonography for at the age of 4.

Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer.

Background & objectives: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD. Methods: Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues. Results: Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC (P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression. Interpretation & conclusions: The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future.

Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts

Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome.

A Novel Germline Mutation of the APC Gene: A Case Report of Familial Adenomatous Polyposis Requiring Repeated Endoscopic Resections for Gastroduodenal Polyps

Familial adenomatous polyposis (FAP) is a precancerous clinical entity, which is characterized by the development of numerous adenomatous polyps throughout the colon and rectum. The majority of FAP are associated with mutations of the adenomatous polyposis coli (APC) gene. Until now, more than 1,000 different APC mutations have been reported and some mutations express attenuated phenotypes which are milder forms with 10~100 colorectal polyps. We identified a novel mutation of APC gene which expressed an attenuated FAP but caused large gastroduodenal tubular adenomas requiring repeated endoscopic resections. A 16-year-old girl was referred to Incheon St. Mary's Hospital for evaluation of gastric polyposis. Initial esophagogastroduodenoscopy (EGD) showed numerous gastric polyps in the fundus and upper body and a few polyps in the duodenum. Pathologic examination confirmed gastric polyps as fundic gland polyps and duodenal polyps as tubular adenomas. Only a few colonic polyps of 2 to 5 mm in size were found on colonoscopy. Genetic analysis using polymerase chain reaction and direct sequencing revealed a novel stop codon mutation at codon 1522 in exon 16 of APC gene. At 12-month, 18-month, and 35-month follow-up EGD, large duodenal polyp and gastric polyps were removed endoscopically.