Mediastinal Abscess Formation after EUS-Guided Sampling in a Young Patient with Sarcoidosis: Be Aware of the Increased Risk!

International guidelines establish EUS-guided sampling as safe and accurate for the evaluation of mediastinal solid lesions, such as lymphadenopathies of unknown origin, and point out an increased risk of severe infectious complications induced by needle puncture in mediastinal cystic lesions. A retrospective case series and a systematic review documented an increased risk of mediastinal abscess formation after EUS-guided lymph nodes sampling in patients with sarcoidosis. The authors describe a case of a 38-year-old male patient with a final diagnosis of sarcoidosis, who developed a large mediastinal abscess after EUS-guided fine-needle biopsy of mediastinal lymphadenopathies. Endoscopists should be aware of the potential increased risk of severe infectious complications when sampling mediastinal lymph nodes in suspected sarcoidosis, and a strategy to minimize such risk should be pursued.

As normas de consenso internacionais estabelecem a biopsia guiada por ecoendoscopia como segura e precisa no diagnóstico de lesões sólidas do mediastino, tais como adenopatias de origem indeterminada, e sublinham o risco significativo de complicações infecciosas graves associado à punção de lesões mediastínicas quísticas. Uma série retrospectiva e uma revisão sistemática apontaram para um risco aumentado de abcesso mediastínico após punção guiada por ecoendoscopia de gânglios linfáticos em doentes com sarcoidose. Os autores descrevem o caso cínico de um jovem de 38 anos, com o diagnóstico final de sarcoidose, que desenvolveu um volumoso abcesso mediastínico após biopsia guiada por ecoendoscopia de adenopatias mediastínicas. Os endoscopistas deverão reconhecer o risco aumentado de complicações infeciosas graves aquando da punção de adenopatias mediastínicas na suspeita de sarcoidose e procurar definir uma estratégia preventiva para minimizar o referido risco.

Endoscopic Reconstruction of an Oral Feeding Route Using a Rendezvous Approach.

Background: The approach to esophageal obstruction or discontinuity remains challenging and often involves complex reconstructive surgeries. The rendezvous endoscopic technique might be interesting in cases of complete esophageal obstruction. Case Presentation: Herein we describe a successful case of endoscopic recanalization of the esophageal lumen in a patient with a long-standing esophageal discontinuity resulting from several surgeries and chemoradiation for a squamous cell carcinoma of the hypopharynx, ending in a major cervical amputation, construction of a neopharynx, and definitive surgical closure of the superior esophagus with a PEG placement. With a rendezvous technique (peroral and through the gastrostomy) and under radiographic guidance, puncture from the neopharynx into the distal esophagus was performed, followed by balloon dilation and covered metal stent placement in order to reconstruct a neoesophagus. Five weeks later, the stent was removed (using a stent-in-stent technique). No complications occurred. The patient has been able to eat soft food and is being kept under regular endoscopic surveillance to control/treat a luminal stenosis of the neoesophagus. Conclusions: This case report illustrates a successful endoscopic treatment of post-surgical complete esophageal obstruction. This approach should be considered in the therapeutic armamentarium of these difficult clinical settings.

Introdução: A abordagem da descontinuidade esofágica permanece desafiante e frequentemente envolve cirurgias reconstrutivas complexas. A técnica endoscópica de rendez-vous pode ser interessante em casos de obstrução esofágica completa. Apresentação do caso: Descrevemos um caso de sucesso de recanalização endoscópica do lúmen esofágico de um doente com descontinuidade esofágica de longa duração, em resultado de múltiplas cirurgias e quimioradiação por um carcinoma pavimento-celular da hipofaringe, que resultou numa amputação cervical major, construção de uma neofaringe e encerramento cirúrgico definitivo do esófago com colocação de PEG. Por técnica de rendez-vous (peroral e por gastrostomia) e sob apoio radiológico, foi realizada punção da neofaringe, seguido de dilatação com balão e colocação de prótese metálica coberta para criar um neo-esófago. Cinco semanas depois, a prótese foi removida (por técnica stent-in-stent). Não ocorreram complicações. O doente tem mantido capacidade de ingerir comida pastosa e é submetido a vigilância regular endoscópica para controlar/tratar uma estenose do lúmen do neo-esófago. Conclusão: Este caso ilustra o tratamento endoscópico bem-sucedido de um doente com obstrução pós-cirúrgica completa do esófago. Esta abordagem deverá ser considerada no arsenal terapêutico destes quadros clínicos complexos.

Endoscopic Management of Symptomatic Duodenal Duplication Cysts: Two Case Reports.

Background: Duodenal duplication cysts (DDCs) are rare congenital anomalies typically manifesting during childhood. Clinical manifestations are uncommon in adulthood. DDCs were classically treated surgically, but endoscopic treatment has been increasingly reported. Endoscopic cyst marsupialization establishes a communication between the cyst cavity and the duodenal lumen so that the cystic content can be drained continuously into the duodenum. We herein describe two cases of symptomatic DDCs diagnosed in adulthood and submitted to endoscopic marsupialization using different techniques and devices. Case Summary: Case 1: A 23-year-old female patient was admitted with the diagnosis of acute pancreatitis. Endoscopic ultrasound revealed a 35-mm duodenal subepithelial lesion whose proximal limit was immediately distal to the ampulla of Vater and filled with fluid and calcifications. Using a duodenoscope, deroofing of the lesion was made with a diathermic snare. Pathology confirmed the diagnosis of DDC. Case 2: A 41-year-old female, submitted to laparoscopic cholecystectomy 1 month earlier due to suspected lithiasic acute pancreatitis, was admitted due to suspicion of iatrogenic biliary fistula. An endoscopic retrograde cholangiopancreatography was performed and the bile leak was treated. Immediately distal to the papillary orifice, a 20-mm subepithelial lesion was also detected. A biopsy forceps was used to fenestrate its wall, allowing the exit of mucous fluid and stones, and a sphincterotome was used to expand the incision. No recurrence was documented in both cases. Conclusion: These cases highlight DDC as a potential cause for acute pancreatitis in adults and endoscopy as an easy treatment option.

Introdução: Os quistos de duplicação duodenais (QDD) são anomalias congénitas raras que tipicamente se manifestam durante a infância. As manifestações clínicas são pouco frequentes em adultos. Os QDD eram classicamente tratados cirurgicamente, mas o tratamento endoscópico tem sido crescentemente reportado. A marsupialização endoscópica do quisto estabelece uma comunicação entre a cavidade do quisto e o lúmen duodenal, permitindo que o conteúdo do quisto drene continuamente para o duodeno. Reportamos 2 casos de QDD diagnosticados em adultos e submetidos a marsupialização endoscópica, utilizando diferentes técnicas e dispositivos. Casos clínicos: Caso 1: Doente do sexo feminino, 23 anos, internada por pancreatite aguda. Por ecoendoscopia documentou-se lesão subepitelial duodenal com 35 mm com limite proximal imediatamente distal à ampola de Vater, preenchida por líquido e calcificações. Usando um duodenoscópio, foi feita marsupialização da lesão com ansa diatérmica. Histologia confirmou o diagnóstico de QDD. Caso 2: Doente do sexo feminino, 41 anos, submetida a colecistectomia laparoscópica 1 mês antes por suspeita de pancreatite aguda litiásica, foi internada por suspeita de fístula biliar iatrogénica. Por CPRE confirmouse fuga biliar que foi tratada. Imediatamente distal ao orifício papilar, foi também detetada uma lesão subepitelial com 20 mm. Uma pinça de biopsia foi usada para fenestrar a sua parede, permitindo a saída de fluido mucoso e cálculos e um esfincterótomo foi usado para expandir a incisão. Não se registou recorrência em nenhum dos casos. Conclusão: Estes casos destacam os QDD como causa potencial de pancreatite aguda em adultos e a endoscopia como possível opção terapêutica.

The Impact of Recent Advances in Endoscopic Ultrasound-Guided Tissue Acquisition on the Management of Pancreatic Cancer.

Over the last few decades, endoscopic ultrasound (EUS)-guided tissue acquisition has become the method of choice for the pathological diagnosis of solid pancreatic lesions. Due to its high diagnostic yield and low complication rate, EUS-guided tissue acquisition has surpassed percutaneous sampling techniques. For many years, EUS-guided fine-needle aspiration (EUS-FNA) was traditionally used to obtain cytological aspirates of solid pancreatic lesions, with sensitivity values ranging from 80 to 90% for the diagnosis of malignancy. Nevertheless, despite numerous technical advances, EUS-FNA still presents some limitations. Therefore, EUS-guided fine-needle biopsy (EUS-FNB) has been introduced to provide tissue core biopsies, allowing histological assessment. A newly developed generation of FNB needles has demonstrated an outstanding diagnostic accuracy of over 95% for solid pancreatic lesions and provides samples appropriate for ancillary testing, such as immunohistochemistry and tumour molecular profiling. As a result, EUS-FNB is rapidly replacing EUS-FNA and is now the recommended technique for EUS-guided tissue acquisition in pancreatic cancer. Furthermore, with the recent expansion of neoadjuvant treatment criteria and with the advent of novel and personalised anti-cancer therapies, EUS-FNB is gaining a pivotal role in pancreatic cancer management and might soon be generalised to all patients, independent of disease stage. In this article, the authors present an updated review of the role of EUS-guided tissue acquisition in pancreatic cancer. Current indications, several technical aspects and new applications of EUS-FNA and EUS-FNB are discussed.

Nas últimas décadas, a aquisição de tecido por ecoendoscopia tornou-se o método de eleição para o diagnóstico patológico de lesões sólidas do pâncreas. Devido à sua elevada capacidade diagnóstica e baixa taxa de complicações, a aquisição de tecido por ecoendoscopia ultrapassou as técnicas de biópsia por via percutânea. Durante muito anos, a aspiração com agulha fina guiada por ecoendoscopia (EUS-FNA) foi tradicionalmente usada para obter aspirados citológicos de lesões sólidas do pâncreas, com valores de sensibilidade que variam entre os 80% e os 90% no diagnóstico de malignidade. Contudo, apesar de numerosos avanços técnicos, a EUS-FNA apresenta ainda algumas limitações. Assim, a biópsia com agulha fina guiada por ecoendoscopia (EUS-FNB) foi introduzida para obter biópsias com cores de tecido, permitindo avaliação histológica. Uma nova geração de agulhas de FNB recentemente desenvolvida demonstra uma acuidade diagnóstica excecional acima de 95% nas lesões sólidas do pâncreas e obtém amostras adequadas para estudos ancilares, designadamente imunohistoquímica e caracterização molecular tumoral. Por conseguinte, a EUS-FNB está rapidamente a substituir a EUS-FNA e é hoje a técnica recomendada para aquisição de tecido no cancro do pâncreas. Além disso, com a recente expansão dos critérios para tratamento neoadjuvante e com o advento de terapias anti-tumorais novas e personalizadas, a EUS-FNB está a adquirir um papel essencial na abordagem do cancro do pâncreas e poderá em breve ser generalizada a todos os doentes, independentemente do estádio da doença. Neste artigo, os autores apresentam uma revisão atualizada do papel da aquisição de tecido por ecoendoscopia no cancro do pâncreas. As indicações atuais, vários aspetos técnicos e novas aplicações da EUS-FNA e EUS-FNB são discutidos.

The Role of Endoscopic Ultrasound in Pancreatic Cancer Staging in the Era of Neoadjuvant Therapy and Personalised Medicine.

Precise staging of pancreatic cancer is crucial for treatment choice. In clinical practice, this includes the TNM staging and determination of tumour resectability, based on a multimodality imaging workup. International guidelines recommend multi-detector computed tomography (CT), with a dedicated pancreatic protocol, as the first-line tool for TNM staging and evaluation of tumour-vessel relationships. In non-metastatic disease upon initial CT assessment, both magnetic resonance imaging and endoscopic ultrasound (EUS) may add relevant information, potentially changing treatment sequence. EUS may have distinct advantages in pancreatic cancer diagnosis and staging when compared with other modalities, being particularly valuable in the determination of portal venous confluence involvement (particularly in small and ill-defined/isoattenuating tumours on CT), in locoregional nodal staging and in the detection of ascites. As we step forward to a more frequent use of neoadjuvant chemotherapy and to personalised medicine, the importance of EUS-guided fine-needle biopsy (EUS-FNB) also increases. The recent availability of third-generation biopsy needles significantly increased the diagnostic yield of EUS-guided tissue acquisition, providing diagnostic cell blocks in approximately 95% of cases with only two dedicated passes and allowing ancillary testing, such as immunohistochemistry and molecular profiling of the tumour. In this article, the authors present an updated perspective of the place of EUS and EUS-FNB in the staging algorithm of pancreatic cancer. Data supporting the increasing role of neoadjuvant therapy and the importance of a patient-tailored treatment selection, based on tumoural subtyping and molecular profiling, are also discussed.

No cancro do pâncreas é fundamental um estadiamento preciso para a decisão terapéutica. Na prática clínica, istoinclui o estadiamento TNM e a avahação da ressecabilidade cirúrgica, baseada numa avahação imagiológica multimodal. As recomendações de consenso recomendam a tomografia computorizada (TC) multi-detector, com protocolo pancreático, como exame de primeira linha para o estadiamento TNM e determinação de invasão vascular loco-regional. Na doença loco-regional não-metastática (após TC inicial), a ressonância magnética e a ecoendoscopia poderão acrescentar informação relevante, com potencial impacto na decisão terapéutica. A ecoendoscopia apresenta vantagens únicas comparativamente a outros métodos de estadiamento, sendo particularmente útil na avahação da relação do tumor com a confluência espleno-portal (especialmente na presença de tumores pequenos e isodensos/mal-definidos na TC), no estadiamento ganglionar loco-regional (N) e na detecção de ascite. À medida que caminhamos no sentido da utilização crescente de quimioterapia neoadjuvante e da Medicina personalizada, a relevância da biopsia guiada por ecoendoscopia também aumenta. A recente disponibilização de agulhas de biopsia de terceira geração aumentou significativamente a rentabilidade diagnóstica da punção guiada por ecoendoscopia, obtendo cell-blocks para avahado histológica em cerca de 95% dos casos (com apenas duas passagens), permitindo a realização de estudos ancilares, como avahação imuno-histoquímica e caracterização molecular do tumor. No presente artigo os autores apresentam uma perspetiva do papel atual da ecoendoscopia e da biopsia guiada por ecoendoscopia no algoritmo de estadiamento do cancro do páncreas. É ainda analisada a evidência atual que favorece o papel crescente da terapéutica neoadjuvante e a importância da seleção individualizada do tratamento, baseada na definição do subtipo de tumor e na caracterizado molecular.

Developments in zebrafish avatars as radiotherapy sensitivity reporters - towards personalized medicine.

BACKGROUND: Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living cancer cells to radiotherapy, using zebrafish xenografts. METHODS: We generated zebrafish xenografts using colorectal cancer cell lines and patient biopsies without in vitro passaging, and developed a fast radiotherapy protocol consisting of a single dose of 25 Gy. As readouts of the impact of radiotherapy we analyzed proliferation, apoptosis, tumor size and DNA damage. FINDINGS: By directly comparing isogenic cells that only differ in the KRASG13D allele, we show that it is possible to distinguish radiosensitive from radioresistant tumors in zebrafish xenografts, even in polyclonal tumors, in just 4 days. Most importantly, we performed proof-of-concept experiments using primary rectum biopsies, where clinical response to neoadjuvant chemoradiotherapy correlates with induction of apoptosis in their matching zebrafish Patient-Derived Xenografts-Avatars. INTERPRETATION: Our work opens the possibility to predict tumor responses to radiotherapy using the zebrafish Avatar model, sparing valuable therapeutic time and unnecessary toxicity.

Sporadic colorectal cancer: Studying ways to an end.

INTRODUCTION: Although colorectal cancer (CRC) has often been regarded as a single entity, different pathways may lead to macroscopically similar cancers. These pathways may evolve into a patchy colonic field defect that we aimed to study in consecutive CRC patients. METHODS: In a single-center, observational, prospective study, consecutive CRC patients were included if surgery and a perioperative colonoscopy were planned. Personal and familial history data were collected. Tumors were studied for microsatellite instability (MSI) status, DNA repair protein expression (DRPE) and presence of BRAF and/or APC mutations. Macroscopically normal mucosa samples were tested for APC mutations. Presence and location of synchronous and metachronous adenomas and patient follow-up were analyzed. The association of two categorical variables was tested through the Fisher's exact test (SPSS 19). RESULTS: Twenty-four patients (12 male, mean age 69 years) were studied. High-grade MSI (MSI-H) was found in eight tumors-these were significantly more common in the right colon (p = 0.047) and more likely to have an altered DRPE (p = 0.007). BRAF mutation was found in two of six tested MSI-H tumors. APC gene mutations were found in nine of 16 non-MSI-H tumors and absent in normal mucosa samples. There was a nonsignificant co-localization of CRC and synchronous adenomas and a significant co-localization (p = 0.05) of synchronous and metachronous adenomas. DISCUSSION: Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non-MSI-H tumors, the expected APC gene mutations were not detected by the most commonly used techniques in a high number of cases. More studies are needed to fully characterize these tumors and to search for common early events in normal mucosa patches, which might explain the indirect evidence found here for a field defect in the colon.

The co-localization of carcinomas and adenomas favors a regional field defect in the colon: an observational study.

PURPOSE: Finding common genetic alterations in colorectal cancers (CRCs) and peri-tumoral mucosa first led to the notion of colonic field defects. The hypothesis of a genetically determined mosaicism would explain these defects and would make the co-localization of tumors likely. Our purpose was to indirectly test this hypothesis by searching for a possible correlation between the location of colorectal cancers and adenomas METHODS: This is a retrospective observational study. Patients operated for colorectal cancers at an oncological hospital, who had a full colonoscopy performed in the two peri-operative years, were surveyed. Sex, age, familial risk of cancer, tumor and adenoma locations, and the presence of adenomas larger than 1 cm, with villous component or high-grade dysplasia were recorded. STATISTICS: T test, chi-square, exact, logistic regression (SPSS18®). RESULTS: This study included 224 patients (57 % male, mean age 67.6 years), 45 % of which had synchronous adenomas. There was a significant correlation between cancer location and location of all adenomas (p = 0.01) and of adenomas larger than 1 cm (p = 0.01). Adenomas of the right colon were more frequent in patients with right colon cancer (p = 0.008), and the same was true on the left colon (p = 0.002). CONCLUSIONS: The strong correlation between the locations of CRC and synchronous adenomas, namely risk adenomas, may point to a common early defect. It does also suggest that hemicolectomy may always be the surgery of choice for colon cancer.

Bone marrow-derived CD11b+Jagged2+ cells promote epithelial-to-mesenchymal transition and metastasization in colorectal cancer.

Timely detection of colorectal cancer metastases may permit improvements in their clinical management. Here, we investigated a putative role for bone marrow-derived cells in the induction of epithelial-to-mesenchymal transition (EMT) as a marker for onset of metastasis. In ectopic and orthotopic mouse models of colorectal cancer, bone marrow-derived CD11b(Itgam)(+)Jagged2 (Jag2)(+) cells infiltrated primary tumors and surrounded tumor cells that exhibited diminished expression of E-cadherin and increased expression of vimentin, 2 hallmarks of EMT. In vitro coculture experiments showed that the bone marrow-derived CD11b(+)Jag2(+) cells induced EMT through a Notch-dependent pathway. Using neutralizing antibodies, we imposed a blockade on CD11b(+) cells' recruitment to tumors, which decreased the tumor-infiltrating CD11b(+)Jag2(+) cell population of interest, decreasing tumor growth, restoring E-cadherin expression, and delaying EMT. In support of these results, we found that peripheral blood levels of CD11b(+)Jag2(+) cells in mouse models of colorectal cancer and in a cohort of untreated patients with colorectal cancer were indicative of metastatic disease. In patients with colorectal cancer, the presence of circulating CD11b(+)Jag2(+) cells was accompanied by loss of E-cadherin in the corresponding patient tumors. Taken together, our results show that bone marrow-derived CD11b(+)Jag2(+) cells, which infiltrate primary colorectal tumors, are sufficient to induce EMT in tumor cells, thereby triggering onset of metastasis. Furthermore, they argue that quantifying circulating CD11b(+)Jag2(+) cells in patients may offer an indicator of colorectal cancer progression to metastatic levels of the disease.

Endoscopic mucosal resection of superficial colorectal neoplasms: review of 140 procedures.

INTRODUCTION AND AIMS: Endoscopic mucosal resection (EMR) has been shown to be useful in the removal of large colorectal sessile and flat lesions, avoiding the need for surgical resection. The aim of this study was to evaluate the efficacy and safety of EMR in colorectal lesions using the inject-and-cut technique. MATERIAL AND METHODS: Based on the review of colonoscopy reports, performed from February 2007 and February 2010, resected lesions = 10 mm in diameter were selected for the study. The endoscopic and histologic characteristics, complications, follow-up and surgical need were recorded. RESULTS: During the study period we performed 140 EMRs among 133 patients (82 men; mean age 64.4 ± 12.4 years). The majority of lesions were located proximal to the hepatic flexure (47.8%). Lesions mean size was 18.5 ± 8.5 mm. Morphologically lesions were classified as: Is-60; IIa-54; IIb-14; IIa+IIc-12. En-bloc resection was performed in 56.4% of cases. Lesions > 20mm in size were independently associated with a higher rate of piecemeal resection (OR: 13.7; 95% CI: 3.8-49.6; p < 0.0001) and residual lesion (OR: 7.3;95% CI: 1.6-34.2; p = 0.012). A complete endoscopic clearance was achieved in 91.4% of cases. Histological classification: non-specific alterations-1; hyperplastic polyp-8; adenoma-124; adenocarcinoma-7. The complication rate was 5.7% (6 intra-procedural bleeding; 1 delayed bleeding; 1 perforation). Until now, 144 follow-up colonoscopies were performed in 90 patients. Local recurrence occurred in 17/90 (18.9%), 10 of whom were managed with a new EMR. The recurrence rate was not affected by the lesion's dimension, location,and resection type. Twenty-one patients (15%) were referred for surgery, mainly because of incomplete resection of the index lesion. CONCLUSION: EMR was effective and safe in the treatment of colorectal sessile and flat lesions. Lesions larger than 20mm were frequently associated with piecemeal resections, which did not lead to a higher recurrence rate. EMR is feasible for managing local recurrence.

Adenoma incidence decreases under the effect of polypectomy.

AIM: To investigate whether, under the influence of polypectomy, the incidence of adenoma decreases with age. METHODS: Consecutive patients with colonic adenomas identified at index colonoscopy were retrospectively selected if they had undergone three or more complete colonoscopies, at least 24 mo apart. Patients who had any first-degree relative with colorectal cancer were excluded. Data regarding number of adenomas at each colonoscopy, their location, size and histological classification were recorded. The monthly incidence density of adenomas after the index examination was estimated for the study population, by using the person-years method. Baseline adenomas were excluded from incidence calculations but their characteristics were correlated with recurrence at follow-up, using the χ(2) test. RESULTS: One hundred and fifty-six patients were included (109 male, mean age at index colonoscopy 56.8 ± 10.3 years), with follow-up that ranged from 48 to 232 mo. No significant correlations were observed between the number, the presence of villous component, or the size of adenomas at index colonoscopy and the presence of adenomas at subsequent colonoscopies (P = 0.49, 0.12 and 0.78, respectively). The incidence of colonic adenomas was observed to decay from 1.4% person-months at the beginning of the study to values close to 0%, at 12 years after index colonoscopy. CONCLUSION: Our results suggest the sporadic formation of adenomas occurs within a discrete period and that, when these adenomas are removed, all neoplasia-prone clones may be extinguished.

Colorectal cancers show distinct mutation spectra in members of the canonical WNT signaling pathway according to their anatomical location and type of genetic instability.

It is unclear whether the mutation spectra in WNT genes vary among distinct types of colorectal tumors. We have analyzed mutations in specific WNT genes in a cohort of 52 colorectal tumors and performed a meta-analysis of previous studies. Notably, significant differences were found among the mutation spectra. We have previously shown that in familial adenomatous polyposis, APC somatic mutations are selected to provide the "just-right" level of WNT signaling for tumor formation. Here, we found that APC mutations encompassing at least two beta-catenin down-regulating motifs (20 a.a. repeats) are significantly more frequent in microsatellite unstable (MSI-H) than in microsatellite stable (MSS) tumors where truncations retaining less than two repeats are more frequent (P = 0.0009). Moreover, in cases where both APC hits are detected, selection for mutations retaining a cumulative number of two 20 a.a. repeats became apparent in MSI-H tumors (P = 0.001). This type of mutations were also more frequent in proximal versus distal colonic tumors, regardless of MSI status (P = 0.0008). Among MSI-H tumors, CTNNB1 mutations were significantly more frequent in HNPCC than in sporadic lesions (28% versus 6%, P < 10-6) and were preferentially detected in the proximal colon, independently of MSI status (P = 0.017). In conclusion, the observed spectra of WNT gene mutations in colorectal tumors are likely the result from selection of specific levels of beta-catenin signaling, optimal for tumor formation in the context of specific anatomical locations and forms of genetic instability. We suggest that this may underlie the preferential location of MMR deficient tumors in the proximal colon.

Aggressive phenotype of MYH-associated polyposis with jejunal cancer and intra-abdominal desmoid tumor: report of a case.

MYH-associated polyposis is an inherited autosomal recessive disease, linked to biallelic germline MYH mutations, which predisposes to the development of multiple colorectal adenomas and cancer. The colonic and extracolonic phenotype of this syndrome is very heterogeneous. We report the case of a young male patient with an aggressive MYH-associated polyposis phenotype. He presented at aged 30 years with more than 100 colonic polyps and 4 colonic adenocarcinomas. At aged 35 years, Spigelman Stage IV duodenal adenomatosis was detected. When he was 39 years old, he developed three synchronous jejunal adenocarcinomas and a mesenteric desmoid tumor. Based on this report, we believe that screening of the entire small bowel should be recommended in MYH-associated polyposis patients, especially in those with duodenal adenomas. Similar to patients with familial adenomatous polyposis, desmoid tumors also may be part of the clinical spectrum of MYH-associated polyposis and may prove to be a significant clinical problem in patients submitted to prophylactic colectomy.

Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients.

BACKGROUND: Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC). OBJECTIVE: We evaluated the association of 3 genetic polymorphisms [C677T MTHFR (methylene tetrahydrofolate reductase), A2756G MTR (methionine synthase), and C1420T SHMT (serine hydroxymethyltransferase)] with the intake of methyl-donor nutrients in CRC risk. DESIGN: Patients with CRC (n = 196) and healthy controls (n = 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms. RESULTS: Except for folate intake, which was significantly lower in patients (P = 0.02), no differences were observed in the dietary intake of other methyl-donor nutrients between groups. High intake of folate (>406.7 microg/d) was associated with a significantly lower risk of CRC (odds ratio: 0.67; 95% CI: 0.45, 0.99). The A2756G MTR polymorphism was not associated with the risk of developing CRC. In contrast, homozygosity for the C677T MTHFR variant (TT) presented a 3.0-fold increased risk of CRC (95% CI: 1.3, 6.7). Similarly, homozygosity for the C1420T SHMT polymorphism also had a 2.6-fold increased risk (95% CI: 1.1, 5.9) of developing CRC. When interactions between variables were studied, low intake of all methyl-donor nutrients was associated with an increased risk of CRC in homozygous participants for the C677T MTHFR polymorphism, but a statistically significant interaction was only observed for folate (odds ratio: 14.0; 95% CI: 1.8, 108.5). No significant associations were seen for MTR or SHMT polymorphisms. CONCLUSION: These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.

[MYH associated polyposis: severe phenotype in the homozygosity for the 1103delC mutation]. / Polipose associada ao MYH: fenótipo grave na homozigotia para a mutação 1103delC.

MYH-associated polyposis (MAP) is an autosomal recessive disease associated with multiple colonic adenomas and colorectal cancer. Y165C and G382D MYH missense mutations are involved in more than 80% of cases in Caucasians and the large series published do not include patients homozygous for other mutations. We present the report of two siblings homozygous for the nonsense frameshift mutation 1103delC. The proband aged 28 presented with four colonic adenocarcinomas and 20-30 synchronous adenomas. Her sister aged 24 had 20 colonic adenomas and a severe Spigelman's III duodenal adenomatosis. Their parents, aged 60 and 51, heterozygous for the 1103delC MYH mutation, presented 5 and 2 low risk colorectal adenomas, respectively.

The D1822V APC polymorphism interacts with fat, calcium, and fiber intakes in modulating the risk of colorectal cancer in Portuguese persons.

BACKGROUND: Both genetic and environmental factors affect the risk of colorectal cancer (CRC). OBJECTIVE: We aimed to examine the interaction between the D1822V polymorphism of the APC gene and dietary intake in persons with CRC. DESIGN: Persons with CRC (n = 196) and 200 healthy volunteers, matched for age and sex in a case-control study, were evaluated with respect to nutritional status and lifestyle factors and for the D1822V polymorphism. RESULTS: No significant differences were observed in energy and macronutrient intakes. Cases had significantly (P < 0.05) lower intakes of carotenes, vitamins C and E, folate, and calcium than did controls. Fiber intake was significantly (P = 0.004) lower in cases than in controls, whereas alcohol consumption was associated with a 2-fold risk of CRC. In addition, cases were significantly (P = 0.001) more likely than were controls to be sedentary. The homozygous variant for the APC gene (VV) was found in 4.6% of cases and in 3.5% of controls. Examination of the potential interactions between diet and genotype found that a high cholesterol intake was associated with a greater risk of colorectal cancer only in noncarriers (DD) of the D1822V APC allele (odds ratio: 1.66; 95% CI: 1.00, 2.76). In contrast, high fiber and calcium intakes were more markedly associated with a lower risk of CRC in patients carrying the polymorphic allele (DV/VV) (odds ratio: 0.50; 95% CI: 0.27, 0.94 for fiber; odds ratio: 0.51; 95% CI: 0.28, 0.93 for calcium) than in those without that allele. CONCLUSION: These results suggest a significant interaction between the D1822V polymorphism and the dietary intakes of cholesterol, calcium, and fiber for CRC risk.