Papillary thyroid carcinoma with desmoid fibromatosis: a case report and review of literature.

Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterized by an unpredictable and variable clinical course. We present the case of a 56-year-old woman who underwent total thyroidectomy for papillary thyroid carcinoma in 2012 and who developed a cervical mass at the left laterocervical level during follow-up, raising the diagnosis of tumor recurrence. Computed tomography of the neck showed solid formations with heterogeneous contrast uptake in the right lateral region of the neck. At the level of the thoracic operculum, a second 26-mm formation was observed that medially contacted the left lateral wall of the trachea. Lateral lymphadenectomy was performed, which was incomplete. Histology showed findings consistent with desmoid-type fibromatosis. DF are slowly proliferating, non-metastatic tumors with a highly invasive capacity that are usually present in familial adenomatous polyposis (FAP)-Gardner syndrome. Our case had a history of massive colonic polyposis and first-degree relatives of colorectal cancer.

La fibromatosis de tipo desmoide (FD) es una rara proliferación fibroblástica monoclonal caracterizada por un curso clínico impredecible y variable. Presentamos el caso de una mujer de 56 años intervenida de tiroidectomía total por carcinoma papilar de tiroides en 2012 y que durante el seguimiento desarrolla una masa cervical a nivel laterocervical izquierdo, planteando el diagnóstico de recidiva tumoral. La tomografía computarizada de cuello demostró formaciones sólidas con captación heterogénea de contraste en la región lateral derecha del cuello. A nivel del opérculo torácico se observó una segunda formación de 26 mm que contactaba medialmente con la pared lateral izquierda de la tráquea. Se realizó una linfadenectomía lateral, que resultó incompleta. La histología mostró hallazgos compatibles con FD. La FD son tumores de proliferación lenta, no metastásicos y con una capacidad altamente invasiva que suelen estar presentes en la poliposis adenomatosa familiar (PAF)-síndrome de Gardner. Nuestro caso tenía antecedentes de poliposis colónica masiva y familiares de primer grado de cáncer colorrectal.

The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis.

Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis

SUMMARY Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

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.

Detection of novel mitochondrial mutations in cytochrome C oxidase subunit 1 (COX1) in patients with familial adenomatous polyposis (FAP).

BACKGROUND: Familial adenomatous polyposis (FAP) is an Autosomal dominant inherited disorder and a rare form| of colorectal cancer (CRC) that is characterized by the development of hundreds to thousands of adenomas in the rectum and colon. Mostly, cancers develop after the advent of the polyps. It appears in both sexes evenly, and the occurrence of the disease is in the second decade of life. Mitochondrial genome mutations have been reported with a variety of Tumors, but the precise role of these mutations in the pathogenicity and tumor progression is not exactly clear. Cytochrome c oxidase subunit I (COX1) is the terminal enzyme of the mitochondrial respiratory chain. The present study aims at assessing the occurrence of mtDNA mutations in COX1 gene in FAP patients and attempts to find out the cause and effect relationship between mitochondrial mutations and tumor progression. METHODS: In this study, 56 FAP patients were investigated for the presence of the mutations in mitochondrial COX1 coding gene by PCR and sequencing analysis. All sequences that differed from the revised Cambridge Reference Sequence (rCRS) were classified as missense/ nonsense or silent mutations. Functional genomic studies using Bio-informatics tools were performed on the founded mutations to understand the downstream alterations in structure and function of protein. RESULTS: We identified 38 changes in the COX1 gene in patients with FAP symptoms. Most of them were heteroplasmic changes of missense type (25/38). Tree of the changes (G6145A, C6988A, and T7306G) were nonsense mutations and had not been reported in the literature before. Our results of bioinformatics predictions showed that the identified mutations can affect mitochondrial functions, especially if the conservative domain of the protein is concerned. CONCLUSION: Our findings indicate a high frequency of mtDNA mutations in all of the FAP cases compared to matched controls. These data significantly enhance our understanding of how such mutations contribute to cancer pathologies and develop the cancer treatment methods by new diagnostic biomarkers, and new drugs for gene therapy.

Molecular basis of familial adenomatous polyposis in the southeast of Brazil: identification of six novel mutations.

BACKGROUND: The goal of this study was to screen point mutations and deletions in APC and MUTYH genes in patients suspected of familial adenomatous polyposis (FAP) in a Brazilian cohort. METHODS: We used high-resolution melting, Sanger direct sequencing and multiplex ligation-dependent probe association (MLPA) assays to identify point mutations, and large genomic variations within the coding regions of APC and MUTYH genes. RESULTS: We identified 19 causative mutations in 40 Brazilian patients from 20 different families. Four novel mutations were identified in the APC gene and two in the MUTYH gene. We also found a high intra- and inter-familial diversity regarding extracolonic manifestations, and gastric polyps were the most common manifestation found in our cohort. CONCLUSION: We believe that the FAP mutational spectrum can be population-specific and screening FAP patients in different populations can improve pre-clinical diagnosis and improve clinical conduct.

iTRAQ-based proteomic analysis of DMH-induced colorectal cancer in mice reveals the expressions of ß-catenin, decorin, septin-7, and S100A10 expression in 53 cases of human hereditary polyposis colorectal cancer.

PURPOSE: The aim of this study is to explore the roles of ß-catenin, decorin, septin-7, and S100A10 expression in colorectal cancer development. METHODS: Twenty-five BALB/c mice were divided into five groups; four groups were administrated N,N-dimethylhydrazine for 0, 10, 15, and 20 weeks, and one group was administrated normal saline for 20 weeks. The colons were collected for histopathological analysis. Protein samples prepared from the frozen colon tissues of mice treated with N,N-dimethylhydrazine for the different time points were evaluated using the isobaric tags for relative and absolute quantification (iTRAQ) labeling technique coupled with the 2D liquid chromatography-tandem mass spectrometry analysis. Based on the proteomic analysis results, immunohistochemical staining of ß-catenin, decorin, septin-7, and S100A10 was performed in paraffin-embedded mice colorectal tissue, and 53 cases of human hereditary polyposis colorectal cancer samples. RESULTS: Colorectal cancer was observed in mice treated with N,N-dimethylhydrazine for 20 weeks, and adenomas were observed in mice subjected to the 10-, and 15-week treatments. Seventy-two differentially expressed proteins were involved in the development of cancer as per the iTRAQ and spectrometry analysis. In normal epithelium, adenoma, and cancer from human hereditary polyposis colorectal cancer, S100A10 expression (c2 = 100.989, P = 0.000) was highest in cancer, whereas decorin (c2 = 12.852, P = 0.002) and septin-7 (c2 = 66.519, P = 0.002) expressions were highest in the normal epithelium, which was confirmed via immunohistochemical staining. CONCLUSIONS: The subcellular localization of ß-catenin and decorin, septin-7, and S100A10 expressions are associated with the development of colorectal cancer in mice after N,N-dimethylhydrazine treatment and in human hereditary polyposis colorectal cancers.

Laparoscopy adjuvant total colorectal resection for the treatment of familial adenomatous polyposis (FAP).

OBJECTIVE: To discuss and evaluate the safety and value of laparoscopy adjuvant total colorectal resection for the treatment of familial adenomatous polyposis (FAP). METHODS: From March 2010 to June 2015, 38 cases were retrospectively analyzed and divided into 2 groups, of which 17 cases used laparoscopy adjuvant total colorectal resection, and 21 cases used conventional laparotomy. Clinical data were obtained, and the safety and prognosis were observed. RESULTS: Seventeen cases using laparoscopy adjuvant total colorectal resection achieved success with no conversion to laparotomy and intraoperative complications. There was no significant difference in operation time between the two groups. There were significant differences in blood loss, the length of incision, postoperative recovery time of intestinal function and postoperative hospital stay between the two groups (P < 0.05). The trauma in laparoscopy group was less, and could recover faster, and there was no significant difference in complications between the two groups. In addition, there were no recurrence, distant metastasis and death in the follow-up period from 6 to 56 months. CONCLUSION: Laparoscopy adjuvant total colorectal resection is more safe and feasible, which has minimal invasion and can recover fast.

Diagnóstico de Cáncer Colorrectal en paciente con sospecha de Poliposis Adenomatosa Familiar / Diagnosis of colonrectal cancer in patient with suspicion of Familial Adenomatous Polyposis

Familial adenomatous polyposis (FAP) is a rare, hereditary disease whose main characteristic is the presence of a large number of polyps in the colon and rectum, which, in the absence of timely treatment, 100% progresses to colorectal cancer. The early diagnosis of this condition is the pillar of the prevention of complications. We present the case of a patient with a low digestive tract syndrome, without previous diagnosis, who after a careful review of clinical and family history, the diagnosis of PAF and later colorectal cancer, is reached. A review of the literature on current advances and recommendations on this disease is made.

Laparoscopic Versus Open Restorative Proctocolectomy for Familial Adenomatous Polyposis.

PURPOSE: This study compared outcomes after laparoscopic (LAP) or conventional (open) total proctocolectomy with outcomes after ileal J-pouch anal anastomosis (IPAA) at a single institution. METHODS: Charts from 133 familial adenomatous polyposis patients (1997-2013) were reviewed. Demographic data (age, sex, color, American Society of Anesthesiologists [ASA] status, previous surgery, and body mass index) and surgical outcomes (length of stay, early and late morbidity, reoperation, and mortality rates) were compared among 63 patients undergoing IPAA. RESULTS: Demographic features were similar among patients (25 open and 38 LAP). Conversely, colorectal cancer at diagnosis prevailed in the open group (60% versus 31.6%; P = .02). Tumor stages (P = .65) and previous surgery index (20% versus 10.5%; P = .46) were similar. Surgical length was longer for LAP (374 versus 281 minutes, P = .003). Short-term complication rates (28% versus 28.9%), hospital stay (10.9 versus 8.9 days), and total long-term reoperations (28% versus 21%) were not statistically different. However, major late morbidity (16% versus 2.6%; P < .001) and late reoperation rates (16% versus 5.2%; P < .05) were greater among open patients. Both groups did not differ regarding pouch failure rates (8% versus 5.2%). There was no operative mortality in the present series. CONCLUSIONS: (1) LAP IPAA is a safe procedure associated with a low conversion rate, (2) short-term results showed no clear advantages for both approaches, and (3) a greater risk of major late complications and late reoperations should be expected after open procedures.

Estrogen Receptor ß as a Prognostic Marker of Tumor Progression in Colorectal Cancer with Familial Adenomatous Polyposis and Sporadic Polyps.

The incidence of colorectal cancer (CRC) is lower in women than in men, and sex steroids can be considered contributing factors because oral contraception usage and estrogen replacement therapy are associated with decreased risk. Conversely, colorectal polyp development in familial adenomatous polyposis (FAP) begins during puberty. The objectives were to evaluate the relationship between the expression of these hormone receptors and adenoma-carcinoma progression, CRC stage and overall survival. We studied 120 A.C. Camargo Cancer Center patients diagnosed with either FAP-associated or spontaneous adenomatous polyps or CRC to determine the immunohistochemical expression levels of estrogen receptor (ER)-α, ER-ß and the progesterone and androgen receptors (480 analyses). The ER-ß expression levels differed between the groups: the group with FAP polyps had lower ER-ß expression than that of the sporadic polyp group. With transformation of the sporadic polyps to cancer, there was a considerable decrease in ER-ß expression (from 90% with strong expression to 80% with absent or weak expression) (p < 0.001). The ER-ß expression was lower in T3/T4 tumors than in T1/T2 tumors (p = 0.015). The 5-year overall survival of CRC patients positively expressing ER-ß exceeded that of patients without detectable expression levels (74.8% vs. 44.3%, respectively; p = 0.035). There was no significant expression of the androgen or progesterone receptor or ER-α among the groups. Differences in ER-ß expression represent a potential mechanism through which estrogen might alter the susceptibility to colon cancer, thereby confirming the possibility of a protective role of estrogen against colorectal carcinogenesis.

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-ß (ERß). The expression of ERß isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. METHODS: This study aimed to investigate the expression levels of the ERß1, ERß2, ERß4 and ERß5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. RESULTS: Decreased expression of ERß isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERß1 and ERß5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERß isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERß was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERß1 and ERß5 expression levels were associated with better disease-free survival (p = 0.002). CONCLUSION: These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

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.

Se justifica el seguimiento después de una colectomía en pacientes con poliposis adenomatosa familiar / The follow up after colectomy in patients with familial adenomatous polyposis is justified

phenotypic expression is the presence of múltiple colorectal adenomatous polyps (more than 100), with high probability developing colorrectal cancer (CRC) before the fifth decade of life. Prophylactic surgery (total colectomy or restorative proctocolectomy) reduces the risk of developing CRC. However, the risk of developing tumors in other organs remains present. Objetive: Analyze the frequency and type of tumors associated with classic familial adenomatous polyposis syndrome (FAPc) patients undergoing prophylactic colectomy. Material and Methods: Cohort study. From the registry of hereditary colorrectal cancer (CRC) at our institution, we identified patients with FAPc who underwent total colectomy with ileorrectal anastomosis (TC-IRA) or restorative proctocolectomy (RTPC), from 1999 to 2014. In the follow-up we analyzed related tumors and mortality. Results: 27 patients, of whom 18 (66.7%) underwent TC-IRA and 9 (33.3%) underwent RTPC. At the time of surgery, 4 patients had CRC (15%) and 5 had extracolonic tumors (osteomas). In a mean follow-up of 49, 4 months (i: 2 y 178) the following lesions were diagnosed: digestive tract adenomas in 17 (63%) patients, of these 2 required a proctectomy and 3 resection of duodenal adenomas. Eight patients developed desmoid tumors (30%), and 3 of them underwent surgery. One patient had an extradigestive tumor (thyroid cancer) and only 8/27 (29.6%) did not develop other tumors. One patient died due to progression of his CCR. Discussion: In this series it is confirmed that most patients will develop neoplasms FAPc after colectomy. conclusion: The removal of the colon and/or rectum is able to prevent the development of CRC. However, two thirds of the patients develop other tumors in which systematic surveillance allowed early detection and treatment.

Objetivo: Analizar la frecuencia y tipo de tumores asociados en pacientes con poliposis adenomatosa familiar clásica (PAFc) sometidos a una colectomía profiláctica. Materiales y Métodos: Estudio de cohorte. Desde el registro de cáncer colorrectal (CCR) hereditario, se identificaron las familias con PAFc, y de estas a los pacientes que se les practicó una colectomía total con anastomosis íleorrectal (CT-AIR) o proctocolec-tomía restauradora (PCTR), desde 1999 al 2014. En el seguimiento se analizaron los tumores asociados y su mortalidad. Resultados: Se identificaron 27 pacientes, de los cuales 18 (66,7%) fueron sometidos a CT-AIR y 9 (33,3%) a PCTR. Al momento de la cirugía, 4 pacientes presentaban CCR (15%) y 5 tenían tumores extracolónicos (osteomas). En un seguimiento promedio de 49,4 meses (i: 2 y 178) se diagnosticaron: adenomas del tracto digestivo en 17 (63%) pacientes, de éstos 2 requirieron una proctectomía y 3 resecciones de adenomas duodenales. Ocho pacientes desarrollaron tumores desmoides (30%), y 3 de ellos fueron sometidos a una cirugía. Un paciente presentó un tumor extradigestivo (cáncer de tiroides) y sólo 8/27 (29,6%) pacientes no desarrollaron otros tumores. Un paciente falleció por progresión de su CCR. Discusión: En esta serie se confirma que la mayoría de los pacientes con PAFc seguirán desarrollando neoplasias después de su colectomía. conclusiones: La extirpación del colon y/o recto permitió evitar el desarrollo de CCR. Sin embargo, dos tercios de los pacientes presentaron otros tumores en quienes su seguimiento permitió una detección y tratamiento temprano.

Risk of thyroid cancer among Caribbean Hispanic patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an inherited form of colorectal cancer characterized by hundreds of adenomatous polyps in the colon and rectum. FAP is also associated with thyroid cancer (TC), but the lifetime risk is still unclear. This study reports the standardized incidence ratio (SIR) of TC in Hispanic FAP patients. TC incidence rates in patients with FAP between the periods of January 1, 2006 to December 31, 2013 were compared with the general population through direct database linkage from the Puerto Rico Central Cancer Registry (PRCCR) and the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). The study population consisted of 51 Hispanic patients with FAP and 3239 with TC from the general population. The SIR was calculated using the Indirect Method, defined as observed TC incidence among patients with FAP in PURIFICAR's cohort (2006-2013) divided by the expected TC incidence based on the PR population rates (2006-2010). SIR values were estimated by sex (male, female, and overall). This study received IRB approval (protocol #A2210207). In Hispanic patients with FAP, the SIR (95% CI) for TC was 251.73 (51.91-735.65), with higher risk for females 461.18 (55.85-1665.94) than males 131.91 (3.34-734.95). Hispanic FAP patients are at a high risk for TC compared to the general population. Our incidence rates are higher than previous studies, suggesting that this community may be at a higher risk for TC than previously assumed. Implementation of clinical surveillance guidelines and regular ultrasound neck screening in Hispanic FAP patients is recommended.

Oral manifestations in patients with familial adenomatous polyposis: A systematic review and meta-analysis.

BACKGROUND AND AIM: The oral manifestations of familial adenomatous polyposis (FAP) have been reported in the recent literature. Therefore, there has been growing interest in the characterization of the dento-osseous anomalies because they may precede colorectal cancer and may be used as a diagnostic marker. This systematic review and meta-analysis was performed to evaluate the published evidence for what are the oral manifestations of FAP and their frequency in affected individuals. METHODS: The search was performed at Cochrane Library, EMBASE, LILACS, PubMed, Scopus, and Web of Science for articles published up to March 2015. A grey literature search was conducted through Google Scholar. Reference lists of the included articles and additional studies identified by expert were screened for potential relevant studies. The methodology of selected studies was evaluated using the risk of bias checklist of the Agency for Healthcare Research and Quality. RESULTS: Twenty observational studies totalizing 1635 individuals affected by FAP met the inclusion criteria. Osseous, dental, and oral mucosa alterations were observed in FAP patients. The meta-analysis showed the frequency of osseous jaw lesions, and the dental anomalies were 65.35% and 30.48%, respectively, and two studies suggested that oral mucosa vascular density is a phenotypic manifestation in patients with FAP. Most of the studies were evaluated as moderate risk of bias. CONCLUSION: The most frequent oral manifestation on FAP patients is osseous jaw alterations. In the future, well-designed studies are necessary to classify osseous and dental anomalies in order to demonstrate the true prevalence of each alteration separately.

MYH polyposis syndrome: clinical findings, genetics issues and management.

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk.

APC germline mutations in families with familial adenomatous polyposis.

Adenomatous polyposis coli (APC) germline mutations are responsible for the occurrence of familial adenomatous polyposis (FAP). Somatic mutations lead to malignant transformation of adenomas. In this context, considering the significance of APC germline mutations in FAP, we aimed to identify APC germline mutations. In the present study, 20 FAP patients were enrolled. The determination of APC germline mutations was performed using sequencing, and the mutations were compared with clinical markers (gender, age at diagnosis, smoking habits, TNM stage, Astler­Coller stage, degree of differentiation of adenocarcinoma). The data were compared using the SPSS program, with the Fisher's exact test and χ2 test, considering α=0.05. According to the main results in our sample, 16 alleles with deleterious mutations (80% of the patients) were identified while 7 (35%) patients had no deleterious mutations. There was a predominance of nonsense (45% of the patients) and frameshift (20% of the patients) mutations. There was no statistical significance between the APC germline mutations identified and the clinical variables considered in our study. Only TNM stage was associated with the presence of deleterious mutations. Patients with deleterious mutations had an OR, 0.086 (IC=0.001-0.984); TNM stage I+II in comparison with III+IV, when compared with the patients with no deleterious mutations identified. In this context, as a conclusion, we demonstrated the molecular heterogeneity of APC germline mutations in FAP and the difficulty to perform molecular diagnostics in a Brazilian population, considering the admixed population analyzed.

Cáncer gástrico temprano o precoz: revisión de la literatura / Early gastric cancer: review of the literature

El cáncer gástrico precoz, se diagnostica cada día con más frecuencia no solo en Japón sino en todo el mundo y, aunque su tratamiento endoscópico es relativamente sencillo, en nuestro medio hay poca experiencia sobre la resección de lesiones sospechosas. El pronóstico de cáncer gástrico temprano es muy bueno y la tasa de supervivencia a los 5 años es del 90%. Por ello, basado en el criterio del tratamiento temprano de cáncer gástrico tiene mejor pronóstico, es importante la detección temprana masiva esta enfermedad antes de que evolucione a un estado avanzado.

Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.