Gastrinomas: advances in diagnosis and management

Gastrinomas causing Zollinger-Ellison syndrome (ZES) are the most common functional, malignant pancreatic endocrine tumors. In this paper, the diagnosis and treatment of these tumors are reviewed, incorporating recent advances in each area. Furthermore, recent advances in their pathology, molecular pathogenesis, and aspects of their localization using somatostatin receptor scintigraphy, as well as their treatment are discussed. Recent data from our NIH prospective studies on patients with ZES are included to illustrate many of these points.     

VIPomas: an update in diagnosis and management in a series of 11 patients

BACKGROUND/AIMS: VIPoma is a rare pancreatic endocrine tumor (PET) which secretes excessive amounts of VIP (Vasoactive Intestinal Peptide) that causes a special clinical syndrome characterized by secretory diarrhea, hypokalemia and achlorhydria. Among a total number of 76 patients (pts) with PETs, we present in this study 11 pts with VIPoma syndrome focusing on our diagnostic and therapeutic approach, in parallel with a brief review of the literature. METHODOLOGY: Eleven pts (7 males and 4 females), aged from 2 to 83 years (mean age 53.1 years) were included. The diagnosis was based upon compatible clinical features and serum VIP values and was supported by the estimation of other peptides and neuroendocrine markers such as gastrin, pancreatic polypeptide and chromogranin-A (CgA). In 10/11 pts, diagnosis was confirmed histopathologically. The primary or metastatic lesions were located by conventional imaging methods or by OCTREOSCAN or Endoscopic Ultrasound (EUS). The follow-up period ranged from 2.5-13.5 years (mean 4.8 years). RESULTS: Chronic secretory diarrhea, which persisted despite fasting, was the main symptom in all pts of our study. VIP levels at the time of diagnosis were more than 3 or 10 times the upper normal limit in 7/11 (63.6%) or 4/11 (36.4%) pts, respectively. The primary lesion was detected by CT scan or MRI in 6/11 (54.5%), with EUS or abdominal angiography in 4/11 (36.4%). OCTREOSCAN revealed a solitary lesion in the right hepatic lobe, not detected by all the previous studies, while it detected, as a whole, the primary lesion in 10/11 (91%), and the metastases in 3/4 (75%) pts. In 7/11 (63.6%) the primary lesion was located in the pancreas, whereas in the rest it was in the duodenum or retroperitoneum. A surgical resection was possible in 7/11 (63.6%) pts, while pts with metastatic disease already or poorly differentiated tumors also received additional treatment with somatostatin analogues and chemotherapy. Liver metastases and poor differentiation of tumors seemed to be negative prognostic factors. CONCLUSIONS: Clinical suspicion, early diagnosis and precise management may affect survival and improve the quality of life of patients. Also, surgical treatment, as extensive as possible, in combination with somatostatin analogues or chemotherapy when necessary, may also result in prolonged survival, also in patients with advanced disease.     

Thoracic outlet syndrome: diagnosis and management with a new surgical technique

In 71 patients with thoracic outlet syndrome, the signs and symptoms of which (Table 1) were assessed revealing several findings previously not reported in association with this condition, 119 surgical procedures were performed according to a newly-developed technique described in this paper. As compared with a substantial number of unsuccessful early and late outcomes rendered through first-rib resection or scalenectomy, the new technique, scalenotomy, led to excellent results in 100% of all cases (Table 2). No complications were seen and no recurrences were observed during an average follow-up period of one year. An additional finding was that, on use of the new technique, even in the presence of a symptomatic cervical rib or hypoplastic first thoracic rib, resection was not necessary to provide the patients with complete recovery from the syndrome.     

Genetic fibrillinopathies: new insights in molecular diagnosis and clinical management

The Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with a prevalence of 2-3 per 10,000 individuals and symptoms ranging from skeletal overgrowth, cutaneous striae to ectopia lentis and aortic dilatation leading to dissection. Mutation in the gene for fibrillin-1 (FBN1) cause MFS and other related disorders of connective tissue, grouped as fibrillinopathies. Fibrillin-1 is the main constituent of extracellular microfibrils. Microfibrils can exist as individual structures or associate with elastin to form elastic fibers. This article provides an overview of the current diagnostic criteria and medical management, estimates the role of fibrillin-1 mutation analysis, sheds new light on genotype-phenotype correlations and summarizes new insights on the pathogenesis of this disorder based on mouse models.     

Current insights in diagnosis and management of the cardiovascular complications of Marfan's syndrome

Marfan's syndrome is an inherited disorder of connective tissue, caused by mutations in the fibrillin-1 gene located on chromosome 15. Diagnosis is still based on a combination of major and minor clinical features. Prognosis is mainly determined by the cardiovascular complications. Advances in surgical and medical treatment for these complications have dramatically improved the prognosis of the syndrome.     

Factors associated with remission in patients with systemic lupus erythematosus: new insights into a desirable state

The primary aim of this study was to assess demographic, clinical, and serological factors associated with remission in systemic lupus erythematosus (SLE). A retrospective cohort study was performed. We examined relevant features in patients with SLE with a follow-up of at least 8 years from active disease (SLE Disease Activity Index-2000 [SLEDAI-2K] ≥6). The primary outcome was to assess various remission states in SLE according to disease activity and treatment. Differences between groups were assessed by Student’s t test and chi-square test for continuous and categorical variables, respectively. Multivariate Cox proportional hazard analysis was used to assess association between variables, and we performed a Kaplan-Meier analysis with log rank test to evaluate time to remission. One hundred twenty-four patients fulfilled our inclusion criteria: 116 (93.54%) were women with a mean age of 30.23?±?8.52 years. Twenty-four patients (19.35%), 25 patients (20.16%), and 16 patients (12.9%) achieved complete remission, clinical remission on corticosteroids, and clinical remission off corticosteroids, respectively. SLEDAI-2K at 3rd month of follow-up (HR?=?0.85, 95% CI?=?0.73–0.98, p?=?0.029) and total number of disease flares (HR?=?0.73, 95% CI?=?0.56–0.95, p?=?0.024) were associated with complete remission, and total number of disease flares (HR?=?0.80, 95% CI?=?0.67–0.95, p?=?0.011) was associated with clinical remission on corticosteroids. Our findings are clinically relevant to encourage an intensive immunosuppressive treatment and close monitoring early after active disease.     

Budd-Chiari syndrome and portal vein thrombosis associated with myeloproliferative disorders: diagnosis and management

The improvement observed in the prognosis of Budd-Chiari syndrome (BCS) since 1985 may be related to a better identification of underlying prothrombotic states. In a recent investigation of the currently identified prothrombotic disorders, one or several prothrombotic disorders were evidenced in 72% of patients with portal vein thrombosis (PVT) and 87% of patients with hepatic vein thrombosis. According to the different criteria used for their diagnosis, myeloproliferative disorders (MPDs) were reported in 25 to 65% of patients with splanchnic vein thrombosis (STV). In a single-center retrospective study of 128 patients with STV, clusters of abnormal megakaryocytes in bone marrow biopsy combined with endogenous erythrocyte colony formation were used as reference standards for a diagnosis of MPD. These two criteria allowed the diagnosis of MPDs at risk of aggravation in 25% (26 of 103) of patients with STV (41% in BCS; 23% in PVT). After a mean follow-up of 6.09 +/- 6.6 years, hematologic progression was confirmed in 23% of patients with the two criteria both positive, whereas neither progression nor features suggestive of MPD were observed in patients with the same concordant negative criteria. The combination of marked splenomegaly and platelet count > 200 x 10 (9)/L that was never observed in patients without MPD, constitutes a simple index for the suspicion of an underlying MPD, but the absence of an obvious splenic enlargement and normal or decreased platelet numbers may even be observed in patients with MPD-associated STV. In the absence of reliable indicators of the exact expansion of the myeloproliferative clone, the therapeutic management of STV-associated MPD is difficult to standardize. Owing to the suspected incidence on the prognosis of BCS of an associated MPD, the present watchful-waiting attitude proposed in MPD without obvious hematologic expression may be challenged.     

Irritable pouch syndrome: a new category of diagnosis for symptomatic patients with ileal pouch-anal anastomosis

OBJECTIVE: Pouchitis often is diagnosed based on symptoms alone. However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome. This study was designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI). METHODS: Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis. Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of <7 and the absence of cuffitis. RESULTS: Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were similar in the three groups. Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups. Rectal bleeding was seen only in cuffitis (p < 0.001). No patient in the three groups had fever. Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3. All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of > or = 1. Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of > or = 1, whereas the remaining patients had persistent symptoms despite therapy. CONCLUSIONS: A substantial number of symptomatic patients after ileal pouch-anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS. There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups. Distinction between these three groups has therapeutic implications.     

Calprotectin in Low anterior resection syndrome patients; a new insight into diagnosis and management: A pilot study

Background and study aimLow anterior resection syndrome (LARS) has been reported to occur in up to 80% of patients after low anterior resection (LAR). This study aimed to investigate the role of fecal calprotectin in the diagnosis of LARS in patients subjected to LAR.Patients and methodsThis was a pilot study conducted on a group of patients that developed LARS after LAR who presented to the colorectal unit of Cairo University Hospital from November 2019 to April 2021. Fecal calprotectin levels were measured for all 36 eligible patients with persistent symptoms of LARS and those with high levels were treated using mesalamine tablets (500 mg, with a total of 3 g per day in divided doses) for one month, then 2 g per day for the subsequent five months.ResultsThe study participants were treated using mesalamine and re-evaluated after six months. Twenty (55.5%) of the 36 patients experienced marked improvement while 10 (27.7%) improved from major to minor LARS with decreased levels of calprotectin. Six (16.6%) patients showed no significant improvement in symptoms (high LARS score) and still had high levels of fecal calprotectin.ConclusionFecal calprotectin can be a useful tool in the diagnosis and treatment planning of persistent LARS. Our study also demonstrated the efficacy of immune modulators such as mesalamine (pentasa) in treating LARS in patients who are unresponsive to conventional dietary restrictions.     

Gastroenteropancreatic neuroendocrine tumors: new insights in the diagnosis and therapy

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively rare and heterogenous malignancies. Recent advances in histopathological classification according to the anatomical site of origin, proliferation rate, and extend of the disease have created a valid and powerful tool for the prognostic stratification of GEP-NETs. Chromogranin A is still the best available marker used for the biochemical confirmation of these tumors, but new more sensitive markers are urgently required. Although scintigraphy with (111)In-octreotide has widely been applied for the localization and staging of GEP-NETs, newer imaging modalities based on the functional characteristics of these tumors are evolving aiming not only to facilitate the diagnosis but also prognosis and evaluation of treatment. Somatostatin receptors are the primary therapeutic targets through somatostatin analogs and peptide receptor radionuclide therapy (PRRT) producing symptomatic, biochemical and to a lesser extent antiproliferative effects. Due to the relatively limited and erratic response to chemotherapy, new molecular targeted therapies exploiting some of the biological properties of GEP-NETs such as increased vascularity and inhibition of pathways involved in downstream signal transduction have evolved. Some of these therapies, the mTOR inhibitor everolimus and the tyrosine kinase inhibitor sunitinib, have been recently validated in phase III studies producing practice changing outcomes. In addition, two oral chemotherapeutic agents temozolomide and capecitabine, show promising effects and may replace streptozotocin-based regimens whereas combination therapies with the angiogenesis inhibitor bevacizumab are being investigated. Although progression free survival is used as a feasible primary end point due to the long survival of patients even in the presence of extensive disease prolongation of overall survival following the introduction of new therapies needs to be established.     

广西新发涂阳肺结核患者确诊延迟影响因素分析

目的分析广西新发涂阳肺结核患者确诊延迟情况及影响因素,为结核病防治工作提供参考。方法从广西现行的4种结核病防治模式单位抽取180例2011年登记报告的新发涂阳肺结核患者的病案信息进行统计分析。结果广西新发涂阳肺结核患者确诊延迟率为44.4％,确诊时间中位数为19 d。 Logistic回归分析显示,男性（ OR＝3.502,P＝0.006）及确诊于CDC模式单位（ OR＝2.797,P＝0.032）的患者发生确诊延迟的风险较大。结论通过加强结核病健康教育,积极出台各项惠民措施,因地制宜地逐步推行结核病诊疗模式转型,有利于减少肺结核患者确诊延迟的发生。     

库欣综合征一线诊断试验的特异性:一个大宗病例的分析

目前,库欣综合征(CS)常常在临床症状充分表现之前就已获诊断,故患者症状轻微.这就要求医生在肥胖、抑郁、高血压和糖尿病患者中排除CS,而这些患者在普通人群中越来越多.