An unconventional retrograde approach for self-expanding metallic stent delivery in oesophagus cancer palliation.

Partially covered self-expanding metallic stents (SEMS) are the main recommendation for palliative treatment of malignant dysphagia. Delivering self-expanding metallic stents in stenosing oesophagus neoplasia's are often challenging due to the difficulty on passing a guide wire through the tumour. We describe a case in which the guidewire was only able to franchise the tumour retrogradely, after entering the gastric cavity through the percutaneous endoscopic gastrostomy orifice using an ultra slim scope.

Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer.

The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear.

Inflammatory Bowel Disease Treatment in Cancer Patients-A Comprehensive Review.

Inflammatory bowel disease (IBD) is a chronic disease for which medical treatment with immunomodulating drugs is increasingly used earlier to prevent disability. Additionally, cancer occurrence in IBD patients is increased for several reasons, either IBD-related or therapy-associated. Doctors are therefore facing the challenge of managing patients with IBD and a past or current malignancy and the need to balance the risk of cancer recurrence associated with immunosuppressive drugs with the potential worsening of IBD activity if they are withdrawn. This review aims to explore the features of different subtypes of cancer occurring in IBD patients to present current evidence on malignancy recurrence risk associated with IBD medical therapy along with the effects of cancer treatment in IBD and finally to discuss current recommendations on the management of these patients. Due to sparse data, a case-by-case multidisciplinary discussion is advised, including inputs from the gastroenterologist, oncologist, and patient.

Incidence and risk factors for neoplasia in inflammatory bowel disease.

INTRODUCTION: Inflammatory Bowel Disease (IBD) patients may have an increased risk of neoplasia. The aim was to evaluate the incidence of malignant neoplasia in IBD patients, associated risk factors and therapy adjustments. METHODS: Unicentric retrospective cohort study. All patients followed for IBD in a tertiary portuguese hospital and oncological centre during 2015-2020 were included. RESULTS: 318 patients were included female 55.0%, age at diagnosis = 37.24(±15,28), Crohn's disease 52.5%, Primary Sclerosing Cholangitis n = 7, family history of cancer n = 12, previous diagnosis of neoplasia n = 23(7.2%). 42 cancers were diagnosed in 35 patients (11.0%) - median of 12.0(IQR = 7.5-21.0) years after IBD diagnosis. Most affected organs were the skin (n = 15 in 11 patients; melanoma = 1), colon/rectum (n = 8 in 6 patients), prostate (n = 4), breast (n = 3) and anal canal (n = 2). In those with non-melanoma skin cancer, 6 were under active treatment with azathioprine and 2 had stopped it for more than two years. In the univariate analysis, the occurrence of neoplasia was positively associated with tobacco exposure (p = 0.022), age at IBD diagnosis (p = 0.021), and negatively with infliximab exposure (p = 0.046). In 9 cases, cancer treatment was different because of the IBD, while IBD treatment was changed in 9 patients. In those affected by cancer, in the univariate analysis, its cure/remission was negatively associated with tobacco exposure (p = 0.004) and positively with salicylates use (p = 0.007). CONCLUSION: In IBD patients, cancer mostly affected the skin and the lower digestive system. As in the general population, tobacco exposure was a risk factor for the development of neoplasia.

Early-onset colorectal cancer: A review of current knowledge.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Although most prevalent among older people, its incidence above 50 years old has been decreasing globally in the last decades, probably as a result of better screening. Paradoxically, its incidence in patients below 50 years old [early-onset CRC (EO-CRC)] has been increasing, for reasons not yet fully understood. EO-CRC's increasing incidence is genre independent but shows racial disparities and has been described to occur worldwide. It follows a birth-cohort effect which probably reflects a change in exposure to CRC risk factors. Its incidence is predicted to double until 2030, which makes EO-CRC a serious public health issue. Both modifiable and non-modifiable risk factors have been identified - some are potential targets for preventive measures. EO-CRC is often diagnosed at advanced stages and histological features associated with poor prognosis have been described. EO-CRC presents some distinctive features: Microsatellite in-stability is common, but another subtype of tumours, both microsatellite and chromosome stable also seems relevant. There are no age-specific treatment protocols and studies on EO-CRC survival rates have shown conflicting data. Due to the higher germline pathological mutations found in EO-CRC patients, an accurate genetic risk evaluation should be performed. In this review, we summarize the current evidence on epidemiological, clinical, histopathological and molecular features of EO-CRC and discuss the contribution of genetics and lifestyle risk factors. We further comment on screening strategies and specific dimensions to consider when dealing with a younger cancer patient.

Can white-light endoscopy or narrow-band imaging avoid biopsy of colorectal endoscopic mucosal resection scars? A multicenter randomized single-blind crossover trial.

BACKGROUND : Current guidelines suggest that routine biopsy of post-endoscopic mucosal resection (EMR) scars can be abandoned, provided that a standardized imaging protocol with virtual chromoendoscopy is used. However, few studies have examined the accuracy of advanced endoscopic imaging, such as narrow-band imaging (NBI) vs. white-light endoscopy (WLE) for prediction of histological recurrence. We aimed to assess whether NBI accuracy is superior to that of WLE and whether one or both techniques can replace biopsies. METHODS : The study was a multicenter, randomized, pathologist-blind, crossover trial, with consecutive patients undergoing first colonoscopy after EMR of lesions ≥ 20 mm. Computer-generated randomization and opaque envelope concealed allocation. Patients were randomly assigned to scar examination with NBI followed by WLE (NBI + WLE), or WLE followed by NBI (WLE + NBI). Histology was the reference method, with biopsies being performed for all tissues. RESULTS : The study included 203 scars (103 in the NBI + WLE group, 100 in the WLE + NBI group). Recurrence was confirmed histologically in 29.6 % of the scars. The diagnostic accuracy of NBI was not statistically different from that of WLE (95 % [95 %CI 92 %-98 %] vs. 94 % [95 %CI 90 %-97 %]; P = 0.48). The negative predictive values (NPVs) were 96 % (95 %CI 93 %-99 %) for NBI and 93 % (95 %CI 89 %-97 %) for WLE (P = 0.06). CONCLUSIONS : The accuracy of NBI for the diagnosis of recurrence was not superior to that of WLE. Endoscopic assessment of EMR scars with WLE and NBI achieved an NPV that would allow routine biopsy to be avoided in cases of negative optical diagnosis.

Transmural remission improves clinical outcomes up to 5 years in Crohn's disease.

INTRODUCTION: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. METHODS: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). RESULTS: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. CONCLUSIONS: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.

Endoscopic Approach to Duodenal Adenomas in Familial Adenomatous Polyposis: A Retrospective Cohort.

Introduction: Over 90% of the patients with familial adenomatous polyposis (FAP) will develop duodenal adenomas. Aim: The aim of this study was to evaluate the effectiveness and safety of endoscopic excision of large duodenal adenomas in FAP patients. Methods: All FAP patients from a familial risk clinic submitted to endoscopic therapy for duodenal adenomas ≥10 mm between January 2010 and February 2021 were included. Results: From 151 FAP families, 22 patients (50 lesions) were included: 54.5% female; median follow-up 8.5 (IQR: 5.8-12.3) years after the first endoscopy. First therapeutic endoscopy occurred at a median age of 41.0 years (IQR: 33.0-58.2). Repeat therapeutic endoscopy was required in 54.5% of patients. Median size of the largest adenoma was 15 mm (IQR: 10-18 mm); resection was piecemeal in 63.1% and en bloc in the remaining. In 2 cases, the resection was incomplete (fibrosis due to previous resection and difficult positioning). Complications occurred in 6.3% of the resected lesions (4 patients): 2 immediate (bleeding, perforation); 4 in the first week (1 bleeding, 2 mild pancreatitis, 1 perforation requiring surgery; the latter two after ampullectomy). Histology revealed low-grade dysplasia adenomas in 90.1%; no adenocarcinomas were found. One patient with Spigelman stage IV disease not amenable to endoscopic control underwent elective duodenopancreatectomy (without duodenal cancer). Conclusion: Endoscopic surveillance and treatment of duodenal adenomas in FAP patients was safe and effective in the prevention of duodenal cancer.

Introdução: Mais de 90% dos doentes com Polipose Adenomatosa Familiar (PAF) desenvolvem adenomas duodenais. Objetivo: Avaliar a eficacia e seguranca da excisao endoscopica de adenomas duodenais em doentes com PAF. Métodos: Incluidos todos os doentes com PAF submetidos a terapeutica endoscopica de adenomas duodenais ≥10 mm entre janeiro/2010-fevereiro/2021. Resultados: Em 151 familias com PAF, incluidos 22 doentes (50 lesoes): 54.5% mulheres; mediana do follow-up 12.3 (IQR: 6.0­19.0) anos. Primeira endoscopia terapeutica (ressecao de polipos duodenais ≥10 mm) ocorreu numa mediana de idades 41.0 (IQR: 33.0­58.2) anos. Em 54.5% dos casos, foi necessaria uma nova endoscopia terapeutica. Dimensao mediana do maior adenoma: 15 mm (IQR: 10­18 mm); ressecao realizada em piecemeal em 63.1% e em bloco nos restantes. Em dois casos, a ressecao endoscopica foi incompleta (fibrose em local de ressecao previa:1; posicionamento: 1). Complicacoes em 6.3% das lesoes ressecadas (4 doentes): 2 imediatas (hemorragia e perfuracao, manejadas endoscopicamente); 4 na primeira semana (1 hemorragia controlada endoscopicamente, 2 pancreatites ligeiras tratadas conservadoramente, 1 perfuracao com necessidade de cirurgia; as duas ultimas apos ampulectomia). A avaliacao histologica revelou adenomas com displasia de baixo grau em 90.1%; nenhum adenocarcinoma. Um doente com doenca Spigelman IV nao controlavel endoscopicamente realizou duodenopancreatectomia (sem cancro). Conclusão: A vigilancia e tratamento endoscopicos de adenomas duodenais em doentes com PAF revelaram-se seguros e eficazes na prevencao de cancro duodenal.

Routine Immunohistochemical Analysis of Mismatch Repair Proteins in Colorectal Cancer-A Prospective Analysis.

Recognition of a hereditary colorectal cancer (CRC) syndrome is crucial and Lynch Syndrome (LS) is the most frequent immunohistochemistry (IHC)-screening for mismatch repair proteins (MMR) deficiency in CRC is therefore advocated. An unicentric cohort study was conducted in a central Oncological Hospital to assess its results. All patients under 70 years-old admitted between July 2017-June 2019 and submitted to surgery for CRC were included. Of 275 patients, 56.0% were male, median age 61.0 (IQR:54.5-65.0), with synchronous tumors in six. Histology revealed high grade adenocarcinoma in 8.4%; mucinous and/or signet ring differentiation in 11.3%; and lymphocytic infiltration in 29.8%. Amsterdam (AC) and Bethesda (BC) Criteria were fulfilled in 11 and 74 patients, respectively. IHC revealed loss of expression of MMR proteins in 24 (8.7%), mostly MLH1 and PMS2 (n = 15) and PMS2 (n = 4). Among these, no patients fulfilled AC and 13 fulfilled BC. BRAF mutation or MLH1 promoter hypermethylation was found in four patients with MLH1 loss of expression. Genetic diagnosis was performed in 51 patients, 11 of them with altered IHC. LS was diagnosed in four, and BC was present in three. One patient would not have been diagnosed without routine IHC screening. These results strengthen the important role of IHC screening for MMR proteins loss of expression in CRC.

Colorectal cancer carcinogenesis: From bench to bedside.

Colorectal cancer (CRC) remains one of the main causes of cancer death in developed countries. Yet, it is potentially preventable, by removing the precursor lesions - adenomas or serrated lesions. Several studies proved that this intervention reduces CRC mortality and that the first colonoscopy's results can guide surveillance strategies. More recently, it became clear that several carcinogenesis pathways may lead to sporadic CRC. CRC is a heterogeneous disease, characterized by multiple molecular subtypes. Three main pathways have been implicated in the development of CRC: Chromosomal instability, microsatellite instability, and the "serrated" pathways, with overlapping features between them. This and other molecular and genetic based CRC classifications are known to have clinical implications, spanning from familial risk assessment to therapy choices. The authors review basic science data and provide insight on current implications for the management of patients with CRC.

A case report of multiple endocrine neoplasia type 1 and autoimmune disease: Coincidence or correlation?

RATIONALE: Multiple Endocrine Neoplasia type 1 (MEN1) is a familial syndrome that results from the disruption of a tumor suppressor protein called MENIN. Its management is challenging, as MEN1 affects different endocrine tissues and predisposes to both benign and malignant tumors. MENIN-deficient cells have recently been recognized to play a role in triggering autoimmunity. Herein, we present a case of MEN1 with multiple endocrine and autoimmune disorders. PATIENT CONCERNS: A 50 years old female with a 25 years history of complicated nephrolithiasis presented with primary hyperparathyroidism. DIAGNOSES: Over several decades, she was diagnosed with recurrent primary hyperparathyroidism, autoimmune thyroiditis, multinodular goiter, pernicious anemia, metastatic gastric type 1 neuroendocrine tumor, macroprolactinemia, gonadotropin deficiency, mucosa-associated lymphoid tissue lymphoma of the thyroid gland, positive anti-calcium sensor receptor antibodies, and BRCA 1/2-negative invasive breast cancer. The autoimmune regulator gene was sequenced, but no pathogenic variants were found. Next-generation sequencing revealed both a pathogenic MEN1 mutation and a benign CDC73 gene variant. Familial genetic screening revealed a large kindred with multiple carriers of one or both genetic variants (MEN1 = 19; CDC73 = 7). INTERVENTIONS: The patient underwent surgical excision of three parathyroid glands, total thyroidectomy and breast tumorectomy plus tamoxifen, and monthly injections of octreotide. The patient and family members with the MEN1 mutation are under a life-long surveillance program for MEN1 prototypic tumors. OUTCOMES: The patient was stable and alive during a 24-years follow-up period. LESSONS: With the present case, the authors highlight a new interplay between MENIN and the immune system, which may have implications for future targeted life-long surveillance and treatment of MEN1 patients.

Pediatric Colorectal Cancer: A Heterogenous Entity.

INTRODUCTION: Colorectal cancer (CRC) is extremely rare in pediatric age. A poor outcome has been reported. AIMS: We aimed to characterize a group of pediatric CRC patients. MATERIALS AND METHODS: All patients with CRC below 18 years old registered in our Familial Cancer Risk Clinic (2002-2016) were included. Clinical and histologic features were evaluated. Germline mutations, microsatellite instability, and DNA mismatch repair proteins expression were analyzed. RESULTS: Five patients were included (3 males; mean age at diagnosis: 14.2 years (range, 9 to 17 y) and 4/5 had family history of cancer in second-degree relatives. With a maximum follow-up of 5.6 years, 2/5 patients died after 10 and 24 months, and 1 recurred after 15 months. All tumors were ≥pT3N2 and 3/5 presented signet ring cells/mucinous histology, corresponding to cases with stronger family history of cancer. Nevertheless, all CRCs analyzed (n=4) were microsatellite stable and/or expressed all mismatch repair proteins. Loss of heterozygosity for the 3 Bethesda dinucleotide markers was detected in 1/3 informative CRCs. A likely pathogenic germline MSH2 mutation was identified in only 1 patient. CONCLUSIONS: Pediatric CRC presented advanced disease and poor prognosis. These tumors had distinct histologic and molecular presentations, resembling features from different carcinogenic pathways, thus suggesting a heterogenous nature.

Real-Time Optical Diagnosis of Colorectal Polyps in the Routine Clinical Practice Using the NICE and WASP Classifications in a Nonacademic Setting.

BACKGROUND: Narrow-band imaging (NBI) allows "in vivo" classification of colorectal polyps. OBJECTIVES: We evaluated the optical diagnosis by nonexpert community-based endoscopists in routine clinical practice, the impact of training, and whether the endoscopists could achieve the threshold for the "do not resect" policy. METHODS: This was an observational study performed in two periods (P1 and P2). Endoscopists had no prior experience in NBI in P1 and applied the technique on a daily basis for 1 year before participation in P2. Lesions were classified by applying the NBI International Colorectal Endoscopic (NICE) and Workgroup serrAted polypS and Polyposis (WASP) classifications, simultaneously. RESULTS: A total of 290 polyps were analyzed. The overall accuracy of optical diagnosis was 0.75 (95% CI 0.68-0.81) in P1, with an increase to 0.82 (95% CI 0.73-0.89) in P2 (p = 0.260). The accuracy of the NICE/WASP classifications to differentiate adenomatous from nonadenomatous histology was 0.78 (95% CI 0.72-0.84) in P1 and 0.86 (95% CI 0.77-0.92) in P2 (p = 0.164); assignments made with a high confidence level achieved statistical significance (13% improvement, 95% CI 3-22%; p = 0.022). The negative predictive value for adenomatous histology of diminutive rectosigmoid polyps was 81% (95% CI 64-93%) and 80% (95% CI 59-93%) in P1 and P2, respectively. CONCLUSIONS: Nonexpert endoscopists achieved moderate accuracy for real-time optical diagnosis of colorectal lesions with the NICE/WASP classifications. The overall performance of the endoscopists improved after sustained use of optical diagnosis, but did not achieve the standards for the implementation of the "do not resect" strategy.

INTRODUÇÃO: O narrow-band imaging (NBI) permite a classificação "in-vivo" dos pólipos colo-rectais. OBJECTIVOS: Avaliámos o diagnóstico óptico na prática clínica diária em endoscopistas da comunidade, sem experiência prévia em NBI, o impacto do treino e se estes conseguiam atingir o limiar da estratégia de "não ressecar". MÉTODOS: Estudo observacional, realizado em dois períodos (P1 e P2). Os endoscopistas não apresentavam experiência prévia em NBI em P1 e aplicaram a técnica diariamente durante um ano antes da participação em P2. As lesões foram classificadas aplicando as classificações NBI International Colorectal Endoscopic (NICE) e Workgroup serrAted polypS and Polyposis (WASP), simultaneamente. RESULTADOS: Foram analisados 290 pólipos. A acuidade global do diagnóstico óptico foi de 0.75 (IC 95%, 0.68-0.81) em P1, aumentando para 0.82 (IC 95%, 0.73-0.89) em P2 (p = 0.260). A acuidade das classificações de NICE/WASP na diferenciação de histologia adenomatosa de não-adenomatosa foi de 0.78 (IC 95%, 0.72-0.84) em P1, e 0.86 (IC 95%, 0.77-0.92) em P2 (p = 0.164); as predições realizadas com alto grau de confiança alcançaram significado estatístico (melhoria de 13%, IC 95%, 3-22%; p = 0.022). O valor preditivo negativo para histologia adenomatosa dos pólipos diminutos recto-sigmóides foi de 81% (IC 95%, 64-93%) e 80% (IC 95%, 59-93%), em P1 e P2, respetivamente. CONCLUSÕES: Endoscopistas sem experiência em NBI alcançaram acuidade moderada no diagnóstico óptico em tempo real de lesões colo-rectais, utilizando as classificações de NICE/WASP. O desempenho global melhorou após a utilização contínua do diagnóstico óptico, mas não alcançou o limiar definido para a implementação da estratégia de "não ressecar".

The nonsense mutation MSH2 c.2152C>T shows a founder effect in Portuguese Lynch syndrome families.

The mutational spectrum of the MMR genes is highly heterogeneous, but specific mutations are observed at high frequencies in well-defined populations or ethnic groups, due to founder effects. The MSH2 mutation c.2152C>T, p.(Gln718*), has occasionally been described in Lynch families worldwide, including in Portuguese Lynch syndrome families. During genetic testing for Lynch syndrome at the Portuguese Oncology Institutes of Porto and Lisbon, this mutation was identified in 28 seemingly unrelated families. In order to evaluate if this alteration is a founder mutation, haplotype analysis using microsatellite and SNP markers flanking the MSH2 gene was performed in the 28 probands and 87 family members. Additionally, the geographic origin of these families was evaluated and the age of the mutation estimated. Twelve different haplotypes were phased for 13 out of the 28 families and shared a conserved region of ∼3.6 Mb. Based on the mutation and recombination events observed in the microsatellite haplotypes and assuming a generation time of 25 years, the age estimate for the MSH2 mutation was 273 ± 64 years. The geographic origins of these families were mostly from the Northern region of Portugal. Concluding, these results suggest that the MSH2 c.2152C>T alteration is a founder mutation in Portugal with a relatively recent origin. Furthermore, its high proportion indicates that screening for this mutation as a first step, together with the previously reported Portuguese founder mutations, may be cost-effective in genetic testing of Lynch syndrome suspects of Portuguese ancestry.

Colorectal cancer surveillance in Portuguese families with lynch syndrome: a cohort study.

PURPOSE: Lynch syndrome (LS) is associated with a high risk of colorectal cancer (CRC). The aim of this study was to assess the cumulative risk for the development of colorectal adenomas or carcinomas in a LS CRC surveillance program and to audit the quality of the endoscopic procedures. METHODS: We evaluated 147 asymptomatic LS mutation carriers, without previous CRC, in a surveillance program with colonoscopy every 12-18 months, between 2005 and 2016. Data was obtained by retrospective review of colonoscopy reports and hospital clinical files. The main outcome was assessed using Kaplan-Meier curves. Logistic regression was used to study the risk of developing adenomas. RESULTS: Patients were under surveillance for 1092 observation years (mean, 7.7 years/patient). Most exams presented adequate bowel preparation (83.5%) and 99.2% achieved cecal intubation. The estimated risk for adenomas at age 60 was 75.6% in men (95%CI, 60.5-88.3) and 65.5% in women (95%CI, 50.8-79.7). Male gender (OR 2.4; 95%CI, 1.2-4.9; p = 0.018) and age at start of surveillance > 40 years (OR 3.7; 95%CI, 1.8-7.7; p < 0.001) were independent risk factors for adenoma detection. CRC was diagnosed in 11 patients with an estimated cumulative risk at age 60 of 18.4% (95%CI, 9.2-34.8%); 72.7% of CRC were classified as stage I; no patient died from CRC. CONCLUSION: A colonoscopic surveillance program in LS patients allowed the detection of adenomas in a large group of mutation carriers and diagnosis of early-stage carcinomas. Our findings may help other teams to adopt similar strategies or to refer patients early to specialized centers.

A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro).

Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.