Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

BACKGROUND: The treatment of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) has evolved with a wider application of neoadjuvant chemotherapy (NACHT). The aim of this study was to identify predictive factors for survival in BR and LA PDAC. METHODS: Clinicopathologic data of patients with BR and LA PDAC who underwent surgical exploration between January 2011 and June 2021 were retrospectively collected. Survival from the date of surgery was estimated using the Kaplan-Meier method. Simple and multiple Cox proportional hazards models were fitted to identify factors associated with survival. Surgical resection was analyzed in combination with the involvement of lymph nodes as this last was only known after a formal resection. RESULTS: Ninety patients were surgically explored (BR: 45, LA: 45), of which 51 (57%) were resected (BR: 31, LA: 20). NACHT was administered to 43 patients with FOLFIRINOX being the most frequent regimen applied (33/43, 77%). Major complications (Clavien-Dindo grade III and IV) occurred in 7.8% of patients and 90-day mortality rate was 3.3%. The median overall survival since surgery was 16 months (95% CI 12-20) in the group which underwent surgical resection and 10 months (95% CI 7-13) in the group with an unresectable tumor (p=0.001). Cox proportional hazards models showed significantly lower mortality hazard for surgical resection compared to no surgical resection, even after adjusting for National Comprehensive Cancer Network  (NCCN) classification and administration of NACHT [surgical resection with involved lymph nodes vs no surgical resection (cHR 0.49; 95% CI 0.29-0.82; p=0.007)]. There was no significant difference in survival between patients with BR and LA disease (cHR= 1.01; 95% CI 0.63-1.62; p=0.98). CONCLUSIONS: Surgical resection is the only predictor of survival in patients with BR and LA PDAC, regardless of their initial classification as BR or LA. Our results suggest that surgery should not be denied to patients with LA PDAC a priori. Prospective studies including patients from the moment of diagnosis are required to identify biologic and molecular markers which may allow a better selection of patients who will benefit from surgery.

Quality of pathology reporting and adherence to guidelines in rectal neuroendocrine neoplasms: a Belgian national study.

The incidence of neuroendocrine neoplasms (NEN) in the rectum is rising since the introduction of colonoscopy screening programs. Guidelines, such as the European NeuroEndocrine Tumor Society (ENETS) algorithm, are mainly based on expert opinion. The goal of this nationwide study is to gain a better insight into the evolution in pathology reporting and adherence to the ENETS guidelines in Belgium. In Belgium, all NENs have to be reported to the Belgian Cancer Registry. We thoroughly reviewed all available pathology reports, coded as rectal NEN between 2004 and 2015, and reclassified according to World Health Organisation (WHO) classification 2019. To evaluate the adherence to the ENETS guidelines, population-based cancer registry data were linked with the medical procedures of the Belgian Health Insurance database. A total of 670 rectal NEN were retained and 16% of the cases needed reclassification. Annual incidence between 2004 and 2015 tripled from 0,20 to 0,61 per 100.000 inhabitants. Reporting of Ki67 proliferation index ameliorated most, while reporting of tumor size, lymphovascular and perineural invasion remained disappointing. Endoscopic ultrasound was performed in only 36.6% of the cases, while the mostly recommended mode of treatment (endoscopic/surgical/no resection) was followed in the majority of the cases. Incidence of rectal NEN in Belgium increased throughout the years and quality of pathology reporting improved especially after the WHO classification update in 2010. The growing awareness and knowledge among clinicians and pathologists in the community counters the need for centralization.

Local control of hepatocellular carcinoma and colorectal liver metastases after surgical microwave ablation without concomitant hepatectomy.

PURPOSE: Microwave ablation (MWA) is an accepted technique in the multimodal treatment of hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM). Study endpoints were to evaluate the local efficacy of surgical MWA in selected patients with oligonodular disease without the combination of liver resection to allow a clear interpretation of the follow-up imaging and compare it to the results on percutaneous MWA available in the literature. METHODS: Consecutive MWA-only procedures performed between May 2013 and May 2018 for HCC and CRLM with free-hand ultrasound guidance were identified. MWA systems with 2450 MHz were used. Incomplete ablation (IA) was defined as residual disease within 1 cm of the ablation site at the first post-ablation imaging and local recurrence (LR) as the presence of disease after at least one tumor-free imaging. RESULTS: A total of 70 tumors in 47 patients were treated with 46 laparoscopic and 1 open procedures. Each patient had no more than 3 tumors, and median size of the lesions was 15 mm (IQR: 10-22). After a median follow-up of 26 months (IQR: 12-40), IA rate was 8.6% and LR rate was 29.4%. Multivariable analysis showed that vascular proximity (OR = 3.4; 95% CI = 1.26-9.22; p=0.016) was the only significant predictor of the combined outcome IA or LR. DISCUSSION: In the present study, after mostly laparoscopic MWA, LR was higher than the rates available in the literature for percutaneous MWA of HCC but lower than in the limited studies analyzing isolated percutaneous MWA of liver metastases. Future developments may help establish the role of each therapeutic modality per tumor, in order to improve the outcomes.

Long term response on Regorafenib in non-V600E BRAF mutated colon cancer: a case report.

BACKGROUND: Non-V600E BRAF mutated colorectal cancer (CRC) is a rare disease entity with specific clinical features. These tumors are less likely to have microsatellite instability than CRC with a V600E BRAF mutation and often harbor a KRAS or NRAS mutation. Notably, median overall survival is longer than in wild-type BRAF CRC. Little is known about treatment possibilities in these patients. CASE PRESENTATION: We present the case of a 59 year old patient with a rare mutation in BRAF codon 594, who progressed rapidly on all classical therapies but experienced a clear and long lasting response on treatment with Regorafenib. CONCLUSION: Little is known about therapies that can be effective in the rare non-V600E BRAF mutated CRCs. We present a patient who had a definite response to treatment with Regorafenib. There are no predictive markers that define a subset of CRC patients who benefit most from Regorafenib. The specific features of this non-V600E BRAF mutated CRC may be relevant in the exploration of predictive biomarkers for the efficacy of Regorafenib.

Colorectal Cancer Screening: What Is the Population's Opinion.

BACKGROUND: Colorectal cancer (CRC) is the first cause of death by cancer in Portugal and mortality has been increasing in the last 30 years. MATERIALS AND METHODS: During a raising awareness campaign performed by our Gastroenterology Department, in Setúbal, Portugal, an anonymous written questionnaire was developed and presented in order to evaluate the population's knowledge and attitude regarding CRC screening. RESULTS: The following results were reported: 140 persons; mean age 54.6 years; 61.4% women; 22.1% had a family history of colorectal cancer. The main risk factors mentioned by the respondents were family history of CRC, previous history of intestinal polyps, and intestinal infection. Screening was considered useful by all respondents. About 60% of the respondents had been counselled, at least, on one screening technique, mainly by their general practitioner: colonoscopy in 31, fecal occult blood test in 44, and flexible sigmoidoscopy in 9. Most of the respondents had had the appropriate screening test, according to their age and family history. Fourteen of the respondents had not undergone the recommended screening. Their answers showed that this was due to fear of pain/discovering a disease as well as embarrassment. CONCLUSION: Although the majority of the respondents were aware of the importance of CRC screening, results show that there are still several misconceptions about risk factors, fear, and reluctance concerning the screening techniques. Awareness actions are useful to clarify possible questions and inform the population in order to increase compliance with screening.

INTRODUÇÃO: O cancro colorretal (CCR) é a primeira causa de morte por cancro em Portugal, com uma mortalidade que tem aumentado nos últimos 30 anos. MATERIAIS E MÉTODOS: Durante uma acção de sensibilização levada a cabo por profissionais de saúde do Serviço de Gastrenterologia, em Setúbal, Portugal, foi realizado um inquérito escrito, anónimo, no sentido de avaliar os conhecimentos e atitudes da população face ao CCR. RESULTADOS: 140 indivíduos; idade média 54.6 anos; 61.4% mulheres; 22.1% tinham pelo menos 1 familiar com CCR. Os factores de risco para CCR mais referidos foram a presença de pólipos e a história familiar. A infecção intestinal foi considerada como um factor de risco para CCR por 74% dos inquiridos, sendo que o rastreio foi considerado útil por todos. Tinha sido recomendado pelo menos um exame de rastreio a cerca de 60% dos participantes, a maioria por indicação do médico assistente de medicina geral e familiar: colonoscopia total em 31, pesquisa de sangue oculto nas fezes em 44 e rectossigmoidoscopia em 9. Atendendo à idade e história familiar, a maioria efectuou um rastreio apropriado. Catorze pessoas não efectuaram o rastreio aconselhado; os motivos mais apontados foram o medo da dor/descobrir uma doença e vergonha. CONCLUSÃO: Embora a maioria dos inquiridos estivesse alerta para a importância do rastreio do CCR, persistem muitas ideias erradas em relação a factores de risco, receios e reticências quanto à realização dos exames de rastreio. Acções de sensibilização são úteis para clarificar dúvidas e informar a população no sentido de aumentar a adesão ao rastreio.

Colonic diverticulosis and the metabolic syndrome: an association?

Background and objectives: Colonic diverticulosis (CD) is related to advanced age and a lack of dietary fiber. Recently, several studies have shown that metabolic syndrome (MS) is also implicated in the etiopathogenesis of CD. This study aimed to assess the association between MS, obesity and CD. Methods: This was a prospective study of a one-year duration. The MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Demographic data, risk factors for MS and endoscopic findings of patients who underwent a total colonoscopy in the department were collected. Obesity was defined as a body mass index ≥ 30 kg/m2. Informed consent was obtained. The local Ethics Committee and National Data Protection Committee approved the study. Statistical analysis was performed with SPSS 21 and statistical significance was defined as p < 0.05. Results: The study included 203 patients, 95 males with a mean age of 65.5 years. CD was diagnosed in 30.5% of patients. Univariate analysis showed that age, hypertension, increased waist circumference and hyperlipidemia were associated with colonic diverticulosis. There was no association with gender, obesity or type 2 diabetes mellitus. Multivariate analysis showed that age and a greater waist circumference increased the risk of diverticulosis. Ageadjusted analysis showed that MS was associated with diverticulosis. The prevalence of adenoma in patients with CD was similar to that in patients without CD. Conclusion: In this series, MS was significantly associated with CD. The identification of risk groups is important since diverticulosis can have serious and potentially fatal complications. To our knowledge, this is the first Southern European prospective study evaluating the association between MS and CD (AU)

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Colonic diverticulosis and the metabolic syndrome: an association?

BACKGROUND AND OBJECTIVES: Colonic diverticulosis (CD) is related to advanced age and a lack of dietary fiber. Recently, several studies have shown that metabolic syndrome (MS) is also implicated in the etiopathogenesis of CD. This study aimed to assess the association between MS, obesity and CD. METHODS: This was a prospective study of a one-year duration. The MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Demographic data, risk factors for MS and endoscopic findings of patients who underwent a total colonoscopy in the department were collected. Obesity was defined as a body mass index ≥ 30 kg/m2. Informed consent was obtained. The local Ethics Committee and National Data Protection Committee approved the study. Statistical analysis was performed with SPSS 21 and statistical significance was defined as p < 0.05. RESULTS: The study included 203 patients, 95 males with a mean age of 65.5 years. CD was diagnosed in 30.5% of patients. Univariate analysis showed that age, hypertension, increased waist circumference and hyperlipidemia were associated with colonic diverticulosis. There was no association with gender, obesity or type 2 diabetes mellitus. Multivariate analysis showed that age and a greater waist circumference increased the risk of diverticulosis. Age-adjusted analysis showed that MS was associated with diverticulosis. The prevalence of adenoma in patients with CD was similar to that in patients without CD. CONCLUSION: In this series, MS was significantly associated with CD. The identification of risk groups is important since diverticulosis can have serious and potentially fatal complications. To our knowledge, this is the first Southern European prospective study evaluating the association between MS and CD.

Haemobilia due to hepatic artery pseudoaneurysm.

An 83-year-old woman with a history of hepaticoduodenostomy 20 years ago was admitted with upper gastrointestinal bleeding. Emergency upper gastrointestinal endoscopy revealed multiple blood clots over the stomach and first and second parts of the duodenum. The cannulation of the biliary tree with a flexible end-viewing endoscope exposed the presence of blood clot inside biliary lumen and a semipedunculated polyp which, at first, appeared to be the cause of haemorrhage. A few days after polypectomy, patient was discharged home, however, was admitted again with massive bleeding and selective angiography demonstrated a pseudoaneurysm of left hepatic artery. Angioembolisation was performed and haemorrhage was stopped afterwards.

Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge.

Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described-olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

Systemic mastocytosis: A rare cause of non-cirrhotic portal hypertension.

Mastocytosis is a clonal neoplastic disorder of the mast cells (MC) that can be limited to the skin (cutaneous mastocytosis) or involve one or more extracutaneous organs (systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis (ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology.

Disseminated Tuberculosis in an Immunocompetent Patient: The Answer is in the Liver.

Tuberculosis, a chronic infectious disease caused by Mycobacterium tuberculosis, may invade all organs but mainly affect the lungs. We report a case of disseminated tuberculosis with hepatic, pericardial and pleural involvement and a review of the relevant literature. A 64-year-old Portuguese male was admitted with epigastric and right upper quadrant pain associated with low grade fever, fatigue, nausea, anorexia, weight loss (6 kg) and mild jaundice. A chest X-ray showed cardiomegaly and a computed tomographic scan of the thorax and abdomen revealed a mild left pleural effusion, a thickened pericardium with signs of incipient calcification and hepatomegaly. The echocardiogram suggested the diagnosis of constrictive pericarditis. Liver biopsy revealed granulomatous lesions with central caseating necrosis. Tuberculosis is usually associated with atypical clinical manifestations. Imaging examination combined with histopathological features, a high index of clinical suspicion and improvement with antibacilar therapeutic are necessary to confirm a diagnosis, especially in the cases of extrapulmonary tuberculosis.

A tuberculose, uma doença infecciosa causada pelo Mycobacterium tuberculosis, pode invadir todos os órgãos, afectando sobretudo os pulmões. Relatamos um caso de tuberculose hepática com envolvimento pericárdico e pleural e uma revisão da literatura relevante. Um homem de 64 anos, de nacionalidade portuguesa, foi admitido por dor no quadrante superior direito do abdómen e no epigastro associada a febre baixa, astenia, náuseas, anorexia, perda de peso (6 kg) e icterícia. A radiografia de tórax revelou cardiomegalia e a tomografia computadorizada de tórax e abdómen revelou um derrame pleural esquerdo ligeiro, um pericárdio espessado com sinais incipientes de calcificação e hepatomegalia. O ecocardiograma era sugestivo de pericardite constritiva. A biopsia hepática revelou granuloma com necrose caseosa central. A tuberculose geralmente está associada a manifestações clínicas atípicas. A presença de aspectos imagiológicos em conjunto com características histológicas típicas, um elevado índice de suspeita clínica e resposta à terapêutica antibacilar são necessários para confirmar o diagnóstico, especialmente nos casos de tuberculose extrapulmonar.

Metabolic syndrome and colorectal neoplasms: An ominous association.

AIM: To evaluate the association of metabolic syndrome (MS) and colorectal cancer and adenomas in a Western country, where the incidence of MS is over 27%. METHODS: This was a prospective study between March 2013 and March 2014. MS was diagnosed according to the National Cholesterol Education Program-ATP III. Demographic characteristics, anthropometric measurements, metabolic risk factors, and colonoscopic pathologic findings were assessed in patients with MS (group 1) who underwent routine colonoscopy at our department. This data was compared with consecutive patients without metabolic syndrome (group 2), with no differences regarding sex and age. Patients with incomplete colonoscopy, family history, or past history of colorectal neoplasm were excluded. Informed consent was obtained and the ethics committee approved this study. Statistical analysis was performed using Student's t-test and χ(2) test, with a P value ≤ 0.05 being considered statistically significant. RESULTS: Of 258 patients, 129 had MS; 51% males; mean-age 67.1 years (50-87). Among the MS group, 94% had high blood pressure, 91% had increased waist circumference, 60% had diabetes, 55% had low high-density lipoprotein cholesterol level, 50% had increased triglyceride level, and 54% were obese [body mass index (BMI) 30 kg/m(2)]. 51% presented 4 criteria of MS. MS was associated with increased prevalence of adenomas (43% vs 25%, P = 0.004) and colorectal cancer (13% vs 5%, P = 0.027), compared with patients without MS. MS was also positively associated with multiple (≥ 3) adenomas (35% vs 9%, P = 0.024) and sessile adenomas (69% vs 53%, P = 0.05). No difference existed between location (P = 0.086), grade of dysplasia (P = 0.196), or size (P = 0.841) of adenomas. In addition, no difference was found between BMI (P = 0.078), smoking (P = 0.146), alcohol consumption (P = 0.231), and the presence of adenomas. CONCLUSION: MS is positively associated with adenomas and colorectal cancer. However, there is not enough information in western European countries to justify screening in patients with MS. To our knowledge, no previous study has evaluated this association in Portuguese patients.

Management of variceal and nonvariceal upper gastrointestinal bleeding in patients with cirrhosis.

Acute upper gastrointestinal haemorrhage remains the most common medical emergency managed by gastroenterologists. Causes of upper gastrointestinal bleeding (UGIB) in patients with liver cirrhosis can be grouped into two categories: the first includes lesions that arise by virtue of portal hypertension, namely gastroesophageal varices and portal hypertensive gastropathy; and the second includes lesions seen in the general population (peptic ulcer, erosive gastritis, reflux esophagitis, Mallory-Weiss syndrome, tumors, etc.). Emergency upper gastrointestinal endoscopy is the standard procedure recommended for both diagnosis and treatment of UGIB. The endoscopic treatment of choice for esophageal variceal bleeding is band ligation of varices. Bleeding from gastric varices is treated by injection with cyanoacrylate. Treatment with vasoactive drugs as well as antibiotic treatment is started before or at the same time as endoscopy. Bleeding from portal hypertensive gastropathy is less frequent, usually chronic and treatment options include ß-blocker therapy, injection therapy and interventional radiology. The standard of care of UGIB in patients with cirrhosis includes careful resuscitation, preferably in an intensive care setting, medical and endoscopic therapy, early consideration for placement of transjugular intrahepatic portosystemic shunt and, sometimes, surgical therapy or hepatic transplant.