Management of early gastrointestinal neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) of the stomach, duo- denum, appendix or rectum that are small (≤ 1 cm) and well differentiated can be considered "early" tumors, since they generally have a (very) good prognosis. In the new WHO classification of 2010, these neoplasms are called neuroendocrine tumors/ carcinoids (NETs), grade (G) 1 or 2, and distinguished from poorly differentiated neuroendocrine carcinomas (NECs), G3. NETs are increasing, with a rise in the age-adjusted incidence in the U.S.A. by about 700 % in the last 35 years. Improved early detection seems to be the main reason for these epidemiological changes. Both the better generalavailability of endoscopy, and imaging techniques, have led to a shift in the discovery of smaller-sized (≤ 10-20 mm) intestinal NETs/carcinoids and earlier tumor stages at diagnosis. Endoscopic screening is therefore effective in the early diagnosis, not only of colorectal adenocarcinomas, but also of NETs/carcinoids. Endoscopic removal, followed up with endoscopic surveillance is the treatment of choice in NETs/carcinoids of the stomach, duodenum and rectum that are ≤ 10 mm in size, have a low proliferative activity (G1), do not infiltrate the muscular layer and show no angioinvasion. In all the other intestinal NENs, optimal treatment generally needs surgery and/or medical therapy depending on type, biology and stage of the tumor, as well as the individual situation of the patient.

Neuroendocrine tumors of the small bowels are on the rise:Early aspects and management

Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today,most neuroendocrine tumors (NETs) of the duodenum are detected "incidentally" and therefore recognized at an early stage. Duodenal NETs which are well differentiated,not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm,for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with longacting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management,tumor biology,type,localization and stage of the neoplasm,as well as the patient's individual circumstances have to be taken into account.

Diagnosis of Zollinger-Ellison syndrome:Increasingly difficult

In the present paper the increasing difficulty of diag-nosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the per-spective of clinical management.

Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia

AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome(MDS) and acute myeloid leukemia (AML) population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients (60.1% male,mean age 61.3 years,13% MDS,87% AML) had 594 unique hospitalizations during the study period.Thirtyfour patients (15.2%) were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001),prior diagnosis of CDI (P < 0.0001),receipt of cytarabine-based chemotherapy (P = 0.015),total days of neutropenia (P = 0.014),and total days of hospitalization (P = 0.005).Gender (P = 0.10),age (P = 0.77),proton-pump inhibitor use (P = 0.73),receipt of antibiotics (P = 0.66),and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.

Identifying who best tolerates moderate sedation:Results from a national database of gastrointestinal endoscopic outcomes

BACKGROUND With increasing volume and cost of gastrointestinal endoscopic procedures,the proper selection of patients for moderate sedation becomes increasingly relevant.The current literature lacks consistent findings that allow for appropriate selection of patients for moderate sedation.AIM To analyze a nationwide registry of patients to identify patient and procedural factors associated with lower sedation requirements for endoscopy.METHODS The Clinical Outcomes Research Initiative National Endoscopic Database was queried to assess adult patients undergoing moderate sedation for esophagogastroduodenoscopy(EGD)and colonoscopy from 2008 to 2014.Patients were stratified into two groups[low dose(LD)and high dose sedation]based on sedation requirements.Anthropometric,procedural,and anesthesia data were compared,and multivariable analysis was performed to identify factors associated with LD sedation.RESULTS Of the 371102 patients included in the study,63137 where stratified into the LD sedation group and 307965 were in the high dose group.Moderate sedation was managed primarily by endoscopists(50%)and anesthesia providers(47%).Patients undergoing EGDs and procedures performed in the inpatient setting,in ambulatory surgery centers,intensive care units or hospital wards,required less sedation than colonoscopies,outpatient procedures and procedures done in endoscopy suites,respectively(P<0.0001 for all).On multivariable analysis,factors predictive of tolerance with lower sedation requirements for EGDs and colonoscopies were female gender,age≥50,non-White race,Hispanic descent,body mass index≤25 kg/m^(2),and higher American Society of Anesthesia Class(P<0.0001 for all).CONCLUSION Clinicians should consider these patient profiles in determining which patients will better tolerate moderate sedation vs those better suited for alternative sedation methods.

丁型肝炎:从最初的发现到如今的治疗研究

丁型肝炎是最严重的病毒性肝炎。与单纯乙型肝炎相比,丁型肝炎向肝硬化进展更快,患肝细胞癌的风险增加,死亡率也更高。尽管丁型肝炎曾经一度被认为已经消失,但随着诊断方法的进步和高发国家移民的增多,该病已成为一个严重的世界性的健康问题。尽管深受关切,但丁型肝炎目前只有唯一一种被接受的治疗药物(聚乙二醇干扰素α),而且该药物疗效并不甚满意,且不良反应明显。因而,许多患者都不去接受治疗。然而,随着对该病毒及其生长周期的认识不断深入,临床上涌现出多种有希望的新药,有望改变丁型肝炎的自然生长,提高治疗效果。本文对丁型肝炎从发现到如今的治疗研究进行文献综述。

维多珠单抗治疗慢性肉芽肿相关炎症性肠病的疗效

Introduction Chronic granulomatous disease(CGD)is a rare immunodeficiency affecting approximately 1 in 200,000 people[1].Patients with CGD are unable to produce normal amounts of neutrophil superoxide and other phagocyte reactive oxygen species.As a result,phagocytes have decreased microbicidal activity and patients develop recurrent bacterial and fungal infections.

Alterations of chromosome 3p in 24 cases of gastrinomas and their correlations with clinicopathological and prognostic features

Purpose::The pathogenesis of gastrinomas is largely unknown,and there is a lack of reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor or predict the prognosis of patients with this disease.Loss of heterozygosity(LOH)on chromosome 3p is reported to occur in pancreatic neuroendocrine tumors(PNETs)as well as in non-PNETs and its presence is reported to correlate with tumor prognosis in non-endocrine tumors.However,little data are available from prospective studies on gastrinomas.Experimental design::We assessed occurrence of 3p LOH in 24 gastrinomas and correlated its presence with tumor biological behavior and other clinicopathological features of gastrinomas.Results::Either 3p LOH or microsatellite instability involving 3p occurred in 11 of 24 tumors(46%).Seven(29%)gastrinomas had 3p LOH.Of the 7 gastrinomas with 3p LOH,5(71%)had 3p12 LOH with the marker D3S2406,which was the shortest region of highest overlap(SRO).Chromosome 3p LOH was not associated with aggressive biological behavior of gastrinomas or with poor prognosis of patients with gastrinoma.Similarly,3p12 LOH(SRO)was not correlated with aggressive growth of tumors and/or liver metastases.Conclusion::Gastrinomas have a relative high frequency of 3p12 LOH suggesting this area may harbor putative tumor suppressor gene(s),which may play a role in the tumorigenesis,but not aggressiveness,of a subset of these tumors.