Abstract Colorectal Cancer (CRC) is the third most common type of cancer worldwide and ranks second in mortality. Screening programs for early detection and treatment have been implemented in several countries. Economic evaluations are an important tool to support decision-making about reimbursement and coverage decisions in health systems and, therefore, to support efficient resource allocation. The article aims to review the up-to-date evidence on economic evaluations of CRC screening strategies. MEDLINE, EMBASE, Web of Science, SCOPUS, SciELO, Lilacs, CRD databases, and lists of references were reviewed to identify relevant literature regarding full economic evaluations of CRC screening in asymptomatic average-risk individuals over 40 years old. Searches were conducted with no restriction to language, setting, or date. Qualitative syntheses described CRC screening strategies and comparators (baseline context), study designs, key parameter inputs and incremental cost-effectiveness ratios. Seventy-nine articles were included. Most of the studies were from high-income countries and a third-party payer perspective. Markov models were predominantly used, although microsimulation has been increasingly adopted in the last 15 years. The authors found 88 different screening strategies for CRC, which differed in the type of technique, the interval of screening, and the strategy, i.e., isolated or combined. The annual fecal immunochemical test was the most predominant screening strategy. All studies reported cost-effective results in their scenarios compared to no screening scenarios. One-quarter of the publications reported cost-saving results. It is still necessary to develop future economic evaluations in Low- and Middle-Income Countries (LMICs), which account for the high burden of disease. (CRC mortality decisionmaking decision making therefore allocation uptodate up date MEDLINE EMBASE Science SCOPUS SciELO Lilacs databases averagerisk average risk 4 old language setting baseline context, context , context) designs costeffectiveness cost effectiveness ratios Seventynine Seventy nine included highincome income thirdparty party perspective used 1 8 technique strategy ie i e i.e. combined costeffective effective Onequarter One quarter costsaving saving Low MiddleIncome Middle Income LMICs, LMICs (LMICs) disease i.e (LMICs

Abstract Fecal Immunochemical Test (FIT) followed by a colonoscopy is an efficacious strategy to improve the adenoma detection rate and Colorectal Cancer (CRC). There is no organized national screening program for CRC in Brazil. The aim of this research was to describe the implementation of an organized screening program for CRC through FIT followed by colonoscopy, in an urban low-income community of São Paulo city. The endpoints of the study were: FIT participation rate, FIT positivity rate, colonoscopy compliance rate, Positive Predictive Values (PPV) for adenoma and CRC, and the rate of complications. From May 2016 to October 2019, asymptomatic individuals, 50-75 years old, received a free kit to perform the FIT. Positive FIT (≥ 50 ng/mL) individuals were referred to colonoscopy. 10,057 individuals returned the stool sample for analysis, of which (98.2%) 9,881 were valid. Women represented 64.8% of the participants. 55.3% of individuals did not complete elementary school. Positive FIT was 7.8% (776/9881). The colonoscopy compliance rate was 68.9% (535/776). There were no major colonoscopy complications. Adenoma were detected in 63.2% (332/525) of individuals. Advanced adenomatous lesions were found in 31.4% (165/525). CRC was diagnosed in 5.9% (31/525), characterized as adenocarcinoma: in situ in 3.2% (1/31), intramucosal in 29% (9/31), and invasive in 67.7% (21/31). Endoscopic treatment with curative intent for CRC was performed in 45.2% (14/31) of the cases. Therefore, in an urban low-income community, an organized CRC screening using FIT followed by colonoscopy ensued a high participation rate, and high predictive positive value for both, adenoma and CRC. (FIT . (CRC) Brazil lowincome low income city PPV (PPV complications 201 2019 5075 75 50-7 old ≥ ( 5 ng/mL ngmL ng mL 10057 10 057 10,05 analysis 98.2% 982 98 2 (98.2% 9881 9 881 9,88 valid 648 64 8 64.8 participants 553 55 3 55.3 school 78 7 7.8 776/9881. 7769881 776/9881 776 (776/9881) 689 68 68.9 535/776. 535776 535/776 535 (535/776) 632 63 63.2 332/525 332525 332 525 (332/525 314 31 4 31.4 165/525. 165525 165/525 165 (165/525) 59 5.9 31/525, 31525 31/525 , (31/525) adenocarcinoma 32 3.2 1/31, 131 1/31 1 (1/31) 29 9/31, 931 9/31 (9/31) 677 67 67.7 21/31. 2131 21/31 21 (21/31) 452 45 45.2 14/31 1431 14 (14/31 cases Therefore both (CRC 20 507 50- 1005 05 10,0 98.2 (98.2 988 88 9,8 6 64. 55. 7. 776988 776/988 77 (776/9881 68. 53577 535/77 53 (535/776 63. 332/52 33252 33 52 (332/52 31. 16552 165/52 16 (165/525 5. 3152 31/52 (31/525 3. 13 1/3 (1/31 93 9/3 (9/31 67. 213 21/3 (21/31 45. 14/3 143 (14/3 100 0 10, 98. (98. 9, 77698 776/98 (776/988 5357 535/7 (535/77 332/5 3325 (332/5 1655 165/5 (165/52 315 31/5 (31/52 1/ (1/3 9/ (9/3 21/ (21/3 14/ (14/ (98 7769 776/9 (776/98 535/ (535/7 332/ (332/ 165/ (165/5 31/ (31/5 (1/ (9/ (21/ (14 (9 776/ (776/9 (535/ (332 (165/ (31/ (1 (21 (776/ (535 (33 (165 (31 (2 (776 (53 (3 (16 (77 (5 (7

RESUMO Contexto A doença de Behçet é uma doença imunomediada rara que pode afetar o trato gastrointestinal. A prevalência e extensão do envolvimento do intestino delgado é desconhecida. Objetivo O objetivo deste estudo foi descrever as lesões do intestino delgado diagnosticadas por enteroscopia de duplo balão (EDB) e verificar se esses achados estavam associados à presença de sintomas gastrointestinais e atividade da doença após seguimento de longo prazo. Métodos Este estudo incluiu 19 pacientes com doença de Behçet que foram submetidos a EDB. Após seguimento médio de 15 anos, os achados endoscópicos foram associados à presença de sintomas gastrointestinais, atividade da doença e terapia atual por meio de coleta de prontuário eletrônico. Resultados Um total de 63,2% dos pacientes eram do sexo feminino e a média de idade era de 37 anos no momento da EDB. A duração média da doença no início do estudo foi de 24 anos. 11 pacientes não apresentaram sintomas gastrointestinais e oito pacientes apresentaram dor abdominal, sangramento gastrointestinal ou diarréia. O tempo médio do procedimento foi de 1 hora e 30 minutos e o íleo foi atingido em todos os pacientes, exceto em um. Úlceras de intestino delgado foram diagnosticadas em 78,9%, sendo 63,1% de acometimento jejunal. Dois pacientes apresentaram apenas edema de intestino delgado e dois apresentaram EDB normais. Oito pacientes tinham úlceras gástricas concomitantes. Sintomas gastrointestinais prévios à EDB estavam presentes em 36,8% dos pacientes e, após o seguimento, todos persistiram com alguns dos sintomas. Sangramento foi relatado por três pacientes no início do estudo e persistiu em apenas um paciente. A frequência de tratamento com esteroides e imunomoduladores foi de 31,6% e 57,9% no início do estudo, respectivamente, e 21% em ambos ao final do seguimento. Nenhum paciente foi tratado com biológicos no momento da EDB e a taxa atual de uso de biológicos é de 21%. Conclusão O envolvimento do intestino delgado na doença de Behçet foi frequentemente demonstrado por EDB mesmo em pacientes assintomáticos. Compreender a evolução clínica da doença ao longo dos anos e o impacto de tal diagnóstico ainda representa um desafio, possivelmente com a necessidade de novos tratamentos.

ABSTRACT Background Behçet’s disease is a rare immune-mediated disorder that can affect the gastrointestinal tract. The prevalence and extension of small bowel involvement is largely unknown. Objective The aim of this study was to describe the small bowel lesions diagnosed by double-balloon enteroscopy (DBE) and to verify if these findings were associated to the presence of gastrointestinal symptoms and disease activity after long-term follow-up. Methods This study included 19 Behçet’s disease patients who underwent DBE. After a mean follow-up of 15 years the endoscopic findings were associated to the presence of gastrointestinal symptoms, disease activity and current therapy through collection of electronic medical records. Results A total of 63.2% patients were female and the mean age was 37 years at the time of DBE. Mean disease duration at baseline was 24 years. 11 patients had no gastrointestinal symptoms and eight patients presented either abdominal pain, gastrointestinal bleeding or diarrhea. The average procedure time was 1 hour and 30 minutes and the ileum was achieved in all patients but one. Small bowel ulcers were diagnosed in 78.9%, with 63.1% of jejunal involvement. Two patients presented only small bowel edema and two were normal by DBE. Eight patients had concomitant gastric ulcers. Gastrointestinal symptoms prior to DBE were present in 36.8% of the patients and, after follow-up, all of them persisted with some of the symptoms. Bleeding was reported by three patients at baseline and persisted in only one patient. The frequency of treatment with steroids and immunomodulators was 31.6% and 57.9% at baseline, respectively, and 21% in both at the end of the follow-up. No patient was treated with biologics at the time of the DBE procedure and the current rate of biologic use is 21%. Conclusion Small bowel involvement in Behçet’s disease was frequently demonstrated by DBE even in asymptomatic patients. Understanding clinical evolution of the disease over the years and the impact of such diagnosis still represents a challenge, possibly with the need for novel treatment.

RESUMO CONTEXTO: A ressecção endoscópica da mucosa é tratamento aceito para o tratamento do câncer gástrico precoce em casos selecionados. Os critérios histopatológicos favoráveis à ressecção endoscópica curativa são adenocarcinomas intramucosos, bem diferenciados, com margens lateral e profunda livres, ausência de ulceração ou de embolização angiolinfática. Taxas de recorrência local próximas a 5% têm sido descritas mesmo quando se cumprem tais critérios. Por outro lado, a expressão antigênica por células tumorais tem sido relacionada com o comportamento biológico de diversos tumores. OBJETIVO: Avaliar se a imunoexpressão de mucinas, p53 e Ki-67 podem predizer a recorrência tumoral após mucosectomia endoscópica no câncer gástrico precoce, mesmo se critérios de cura histopatológicos forem atingidos. MÉTODOS: Vinte e dois pacientes com critérios de cura para ressecção endoscópica e sumetidos a mucosectomia foram selecionados. A recorrência local ocorreu em 5/22 (22,7%). O estudo imunohistoquímico foi realizado em 18 (81,8%) espécimens. Os pacientes foram divididos em grupos com e sem recorrência local. Foram comparados quanto a dados demográficos, endoscópicos, histológicos e fatores imunohistoquímicos para MUC2, MUC5A, CD10, p53, e Ki-67. RESULTADOS: A imunoexpressão de mucinas permitiu a reclassificação dos adenocarcinomas gástricos em intestinal (10), gástrico (2), e de fenótipo misto (4) e nulo (2). Os fenótipos mistos (positivos tanto para MUC2 quanto para MUC5A) foram encontrados em 80% dos casos no grupo de recorrência local, enquanto tipos intestinais (MUC2 positivo e MUC5A negativo) foram identificados em 76,9% dos casos sem recorrência (P=0,004). Os outros fatores observados não se relacionaram com a recorrência tumoral. CONCLUSÃO: O fenótipo misto do câncer gástrico precoce está associado a maior probabilidade de recorrência local após a mucosectomia.

ABSTRACT BACKGROUND: Endoscopic mucosal resection is still considered an accepted treatment for early gastric cancer for selected cases. Histopathologic criteria for curative endoscopic resection are intramucosal well-differentiated adenocarcinoma, lateral and deep margins free of tumor, no histological ulceration, and no venous or lymphatic embolism. A 5% local recurrence rate has been described even when all the above-mentioned criteria are met. On the other hand, antigen expression by tumoral cells has been related to the biological behavior of several tumors. OBJECTIVE: To evaluate whether early gastric cancer mucin immunoexpression, p53 and Ki-67, can predict recurrence after endoscopic mucosal resection, even when standard histopathologic criteria for curative measures have been attempted. METHODS: Twenty-two patients with early gastric cancer were considered to have been completely resected by endoscopic mucosal resection. Local recurrence occurred in 5/22 (22.7%). Immunohistochemical study was possible in 18 (81.8%) resected specimens. Patients were divided in two groups: those with and those without local recurrence. They were compared across demographic, endoscopic, histologic data, and immunohistochemical factors for MUC2, MUC5a, CD10, p53, and Ki-67. RESULTS: Mucin immunoexpression allowed a reclassification of gastric adenocarcinoma in intestinal (10), gastric (2), mixed (4), and null phenotypes (2). Mixed phenotype (positive for both MUC2 and MUC5a) was found in 80% of cases in the local recurrence group, while the intestinal type (positive MUC2 and negative MUC5a) was found in 76.9% of cases without local recurrence (P=0.004). Other observed features did not correlate with neoplastic recurrence. CONCLUSION: The mixed phenotype of early gastric adenocarcinoma is associated with a higher probability of local recurrence after endoscopic mucosal resection.

ResumoHiperinfecção por Strongyloides stercoralis: uma causa incomum de hemorragia digestiva A estrongiloidíase é uma parasitose que pode evoluir para uma forma disseminada, denominada síndrome de hiperinfecção, nos pacientes em estados de imunossupressão. A síndrome de hiperinfecção é ocasionada pela grande multiplicação e migração de larvas infectantes, com envolvimento gastrointestinal e/ou pulmonar característico. Essa doença pode representar um desafio diagnóstico, pois apresenta- se em achados inespecíficos à endoscopia.

SummaryStrongyloidiasis is a parasitic disease that may progress to a disseminated form, called hyperinfection syndrome, in patients with immunosuppression. The hyperinfection syndrome is caused by the wide multiplication and migration of infective larvae, with characteristic gastrointestinal and/or pulmonary involvement. This disease may pose a diagnostic challenge, as it presents with nonspecific findings on endoscopy.

Contexto Adenoma gástrico é uma lesão precursora do adenocarcinoma. Objetivo Melhor caracterizar os adenomas de acordo com a imunoexpressão de mucinas e avaliar a imunoexpressão de p53, p16ink4a, BCL-2, cyclin D, Ki-67, nos adenomas e na mucosa gástrica adjacente. Métodos Quarenta espécimes gástricos provenientes de 20 pacientes portadores de adenomas foram classificados como do tipo intestinal (MUC2 – mucina presente nas células caliciformes) ou gástrico (MUC5AC – mucinas de padrão foveolar). Realizou-se imunoistoquímica para p53, p16ink4a, BCL-2, cyclin D e Ki-67 pelo método do complexo da estreptavidina-biotina. Resultados Doze (60%) pacientes eram homens e a média de idade foi de 67,9 ± 12,9 anos. Os adenomas foram classificados como do tipo intestinal em 13 (65%) pacientes e do tipo gástrico em 7 (35%). Displasia (neoplasia intraepitelial) de baixo grau estava presente em 13 (65%), displasia de alto grau em 3 (15%), e adenocarcinoma no pólipo adenomatoso em 4 (20%) pacientes. Observou-se immunoexpressão do p53 em 6/20 (30%) adenomas, e em 2/6 (33,3%) dos tumores sincrônicos. Houve associação entre imunoexpressão do p53 e adenoma/tumor tipo intestinal, P = 0.04. Não houve associação entre imunoexpressão do p16ink4a, Bcl-2, ciclina D e Ki-67 e as características clinicopatológicas dos adenomas. Conclusão Imunoistoquímica pode ser utilizada para caracterizar os subtipos de adenoma e talvez indicar o caminho de carcinogênese.

Context Gastric adenoma is a precursor lesion of the adenocarcinoma. Objective To characterize gastric adenomas according to the mucin immunoexpression and to evaluate the immunoexpression of p53, p16ink4a, BCL-2, cyclin D, Ki-67, in the adenoma and in the gastric mucosa harboring adenoma. Methods Forty gastric specimens from 20 patients were classified as intestinal (MUC2 - goblet cell mucin) or foveolar (MUC5AC - gastric-foveolar mucin) adenomas. Immunohistochemistry was performed using streptavidin-biotin-complex method. Results Twelve (60%) patients were men. The mean age was 67.9 ± 12.9 years-old. Intestinal adenomas were detected in 13 (65%) patients and gastric type in 7 (35%). Low-grade dysplasia was present in 13 (65%) of the adenomas, high-grade in 3 (15%), and adenocarcinoma within the polyp in 4 (20%). Six (30%) patients had synchronous adenocarcinoma. p53 immunoexpression was observed in 6/20 (30%) of adenomas, and in 2/6 (33.3%) of synchronous tumors. There was an association between p53 immunoexpression and intestinal type of adenoma/tumor, P = 0.04. There was no association between p16ink4a, Bcl-2, cyclin D and Ki-67 and adenoma clinicopathological characteristics. Conclusion Immunohistochemistry may be useful to classify the adenomas subtypes and may define the pathway of adenoma to carcinoma sequence.

Racional - Pacientes submetidos a ressecção gástrica parcial apresentam risco aumentado de desenvolvimento de câncer de coto gástrico. Objetivo - Analisar, a longo prazo, as alterações da mucosa de pacientes submetidos previamente a tratamento cirúrgico, por úlcera péptica. Pacientes e Métodos - No período de 1987 a 1990, 154 pacientes (média de 20,4 anos após gastrectomia) foram analisados através de exames endoscópicos com múltiplas biopsias, e histopatológicos. Resultados - Alterações endoscópicas estiveram presentes em 111 pacientes (72,1%) e as mais freqüentemente encontradas foram: hiperplasia foveolar, metaplasia intestinal e dilatação cística. Displasia intensa foi diagnosticada em 2 (1,25%) e carcinoma em 13 (8,4%) dos casos. Em quatro pacientes (3,8%), o método endoscópico não revelou lesão tumoral, contudo, foi detectada neoplasia no estudo histológico do material de biopsia. Conclusão - A vigilância dos pacientes gastrectomizados, através de procedimento endoscópico com múltiplas biopsias, pode diagnosticar neoplasia em estádio inicial; entretanto, novos estudos são necessários para se estabelecer a relação custo-benefício da referida estratégia de detecção.

Background - Patients who underwent partial gastric resections are at an increased risk for the development of cancer in the gastric remnant. Aim - To assess the long-term patients who underwent surgical treatment for peptic ulcer disease through endoscopic and pathologic evaluation of the gastric stump mucosal alterations. Patients and Methods - Between 1987 and 1990, 154 patients (mean = 20.4 years after gastrectomy) were evaluated by upper digestive endoscopy with multiple biopsies and pathological examination. Results - Endoscopic alterations were present in 111 patients (72.1%). The commonest pathologic alterations were foveolar hyperplasia, intestinal metaplasia and cystic dilation. Severe dysplasia was noted in two (1.25%) and carcinoma in 13 (8.4%) of the cases. In four patients (3.8%) the endoscopic findings did not show any evidence of tumors, however they were detected due to multiple biopsies and histologic studies. Conclusions - Surveillance of these patients with endoscopy and multiple biopsies may provide the means to diagnose tumors at an early stage, but the cost benefit ratio of surveillance requires further study.

Carcinoma epidermóide do esôfago está freqüentemente associado a outros, sincrônicos ou metacrônicos tumores do trato aerodigestivo alto. Foram analisados, retrospectivamente, 264 pacientes com carcinoma de esôfago tratados na Disciplina de Cirurgia do Aparelho Digestivo, Divisão de Cirurgia do Esôfago, do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, entre 1979 e 1989, com o intuito de se observar a ocorrência de múltiplos tumores primários do trato aerodigestivo alto. Observaram-se 10 (3.8%) pacientes com múltiplos tumores primários. Todos eram do sexo masculino e a média de idade ao tempo do primeiro tumor foi 52.2 anos. Os locais dos tumores primários foram: laringe (n = 4), língua (n = 3), pulmão (n =2), cavidade oral (n = 1) e esôfago (n = 1). Dois tumores eram simultâneos, três sincrônicos e cinco metacrônicos. O esôfago foi o segundo tumor primário em nove pacientes. A sobrevida média depois do diagnóstico do segundo tumor primário foi de apenas 2.8 meses (DP = 0.89). Na tentativa de se diagnosticar outros tumores, o exame clínico associado com panendoscopia deve ser realizado antes de se tratar o tumor inicial, a fim de que se possa diagnosticar tumores simultâneos ou sincrônicos. Ademais, deve ser realizado cuidadoso seguimento após o tratamento do primeiro tumor pois estes pacientes apresentam risco de aparecimento de novos tumores.

Squamous cell carcinoma of the esophagus is frequently associated with other, synchronous or metachronous tumors, in the upper aerodigestive tract. All 264 patients with squamous cell carcinoma of the esophagus, treated in the Gastrointestinal Surgery, Esophagus section, of the "Hospital das Clínicas" (São Paulo University Medical School, Brazil), between 1979 and 1989 were analyzed retrospectively with regards to the occurrence of multiple primary tumors in the upper aerodigestive tract. Multiple primary tumors were encountered in 10 (3.8%) patients. All patients were male and the mean age at the time of the first primary was 52.2 years. Tobacco smoke and alcohol were the principal carcinogens in these patients (n = 10). The sites of the tumors were: larynx (n = 4), tongue (n = 4), lung (n = 2), and oral cavity (n = 1). Two simultaneous, three synchronous and five metachronous multiple primary carcinomas were detected. The esophagus was the second primary tumor in nine patients. The mean overall survival after the diagnosis of the second primary was 2.8 months (SD = 0.89). Inquiry regarding other malignancies, associated with panendoscopy should be carry out prior to the treatment of the first primary to diagnose simultaneous or synchronous primary tumors, and careful follow-up should be performed after treatment of the first primary to detect new tumors in these high-risk patients.

Duplo piloro é condição rara em que se forma dupla comunicação entre o antro gástrico e o bulbo duodenal. Pode ser congênito ou adquirido como complicação de doença cloridropéptica. Apresentamos caso de duplo piloro adquirido em paciente masculino com epigastralgia e história prévia de úlcera péptica. A pesquisa do Helicobacter pylori foi positiva em amostras de tecido gástrico. Foi realizada revisão da literatura e discutido o papel de doenças associadas e do Helicobacter pylori na etiopatogenia desta afecção.

Double pylorus is an unusual condition in which a double communication between the gastric antrum and the duodenal bulb occurs. It may be congenital, or it may be acquired complication of peptic ulcer disease. We present a case of double pylorus in a gentleman with epigastric pain and previous history of peptic ulcer disease. The relationship between Helicobacter pylori and this disease was assessed. A review of the literature, the role of associated diseases and the role of H. pylori are discussed.