Cryoballoon ablation as salvage therapy after nonradical resection of a high-risk T1b esophageal adenocarcinoma: a case report.

Although esophagectomy with or without (neo)adjuvant chemoradiation therapy is the current standard of care for patients with early esophageal adenocarcinoma with high-risk features or after nonradical endoscopic resection of an early esophageal adenocarcinoma, not all patients are eligible for surgery due to varying reasons. In these patients, cryoballoon ablation may serve as an alternative treatment option considering the potential of deeper tissue ablation as compared to heat-based ablation techniques. We report the first case in which cryoballoon ablation was successfully performed as salvage therapy with a curative intent for positive deep resection margins after an incomplete endoscopic resection of a recurrent early esophageal adenocarcinoma.

Surgery in (pre)malignant celiac disease.

AIM: To report the outcome of surgery in patients with (pre)malignant conditions of celiac disease (CD) and the impact on survival. METHODS: A total of 40 patients with (pre)malignant conditions of CD, ulcerative jejunitis (n = 5) and enteropathy associated T-cell lymphoma (EATL) (n = 35), who underwent surgery between 2002 and 2013 were retrospectively evaluated. Data on indications, operative procedure, post-operative morbidity and mortality, adjuvant therapy and overall survival (OS) were collected. Eleven patients with EATL who underwent chemotherapy without resection were included as a control group for survival analysis. Patients were followed-up every three months during the first year and at 6-mo intervals thereafter. RESULTS: Mean age at resection was 62 years. The majority of patients (63%) underwent elective laparotomy. Functional stenosis (n = 13) and perforation (n = 12) were the major indications for surgery. In 70% of patients radical resection was performed. Early postoperative complications, mainly due to leakage or sepsis, occurred in 14/40 (35%) of patients. Eight patients required reoperation. More patients who underwent resection in the acute setting (n = 3, 20%) died compared to patients treated in the elective setting. With a median follow-up of 20 mo, seven patients (18%) required reoperation due to long-term complications. Significantly more patients who underwent acute surgery could not be treated with adjuvant chemotherapy. Patients who first underwent surgical resection showed significantly better OS than patients who received chemotherapy without resection. CONCLUSION: Although the complication rate is high, the preferred first step of treatment in (pre)malignant CD consists of local resection as early as possible to improve survival.

A New and Validated Clinical Prognostic Model (EPI) for Enteropathy-Associated T-cell Lymphoma.

PURPOSE: Enteropathy-associated T-cell lymphoma (EATL) is a rare intestinal non-Hodgkin lymphoma with a poor, though variable prognosis. The International Prognostic Index (IPI) and the prognostic index for peripheral T-cell lymphoma (PIT) have limited predictive value for outcome of EATL. The purpose of this study was to develop and validate a prognostic model for EATL, which can identify high-risk patients who need more aggressive therapy. EXPERIMENTAL DESIGN: This retrospective multicenter study was based on 92 patients and included 45 patients diagnosed with EATL between 1999 and 2009 from the Netherlands and 47 patients from England and Scotland, diagnosed with EATL between 1994 and 1998. A new EATL prognostic index (EPI) was constructed using the RPART (recursive partitioning and regression trees) procedure. Validation was performed applying the bootstrap method. RESULTS: Three risk groups were distinguished (P < 0.0001): a high-risk group, characterized by the presence of B-symptoms [median overall survival (OS) of 2 months]; an intermediate-risk group, comprising patients without B-symptoms and an IPI score ≥ 2 (7 months); and a low-risk group, representing patients without B-symptoms and an IPI score of 0 to 1 (34 months). Internal validation showed stability of statistical significance and prognostic discrimination. In contrast with the IPI and PIT, the EPI better classified patients in risk groups according to their clinical outcome. CONCLUSIONS: Our new, validated, prognostic model EPI accurately predicts survival outcome in EATL and may be used for patient selection for new therapeutic strategies and evaluation of clinical trials.

Consumption of gluten with gluten-degrading enzyme by celiac patients: a pilot-study.

AIM: To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients. METHODS: Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and mucosal healing classified as Marsh 0 or I were included. In a randomised double-blind placebo-controlled pilot study, patients consumed toast (approximately 7 g/d gluten) with AN-PEP for 2 wk (safety phase). After a 2-wk washout period with adherence of the usual GFD, 14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk (efficacy phase). Measurements at baseline included complaints, quality-of-life, serum antibodies, immunophenotyping of T-cells and duodenal mucosa immunohistology. Furthermore, serum and quality of life questionnaires were collected during and after the safety, washout and efficacy phase. Duodenal biopsies were collected after the safety phase and after the efficacy phase. A change in histological evaluation according to the modified Marsh classification was the primary endpoint. RESULTS: In total, 16 adults were enrolled in the study. No serious adverse events occurred during the trial and no patients withdrew during the trial. The mean score for the gastrointestinal subcategory of the celiac disease quality (CDQ) was relatively high throughout the study, indicating that AN-PEP was well tolerated. In the efficacy phase, the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed. During the efficacy phase, neither the placebo nor the AN-PEP group developed significant antibody titers. The IgA-EM concentrations remained negative in both groups. Two patients were excluded from entering the efficacy phase as their mucosa showed an increase of two Marsh steps after the safety phase, yet with undetectable serum antibodies, while 14 patients were considered histologically stable on gluten with AN-PEP. Also after the efficacy phase, no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP. Furthermore, IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo. In the seven patients receiving AN-PEP, one patient showed increased and one showed decreased IgA-tTG deposits. CONCLUSION: AN-PEP appears to be well tolerated. However, the primary endpoint was not met due to lack of clinical deterioration upon placebo, impeding an effect of AN-PEP.

Enteropathy associated T-cell lymphoma and its precursor lesions.

Enteropathy Associated T-cell Lymphoma (EATL) is an intestinal tumour of intra-epithelial lymphocytes. Based on morphology, immunohistochemistry and genetic profile EATL can be divided into two groups. EATL type I is a large cell lymphoma which is highly associated with Coeliac Disease (CD) and mostly presents with malabsorption, weight loss and CD-related symptoms. EATL type II consists of small to medium-sized cells and presents often with obstruction or perforation of the small bowel. This type of EATL has no known association with CD. When EATL has been diagnosed a thorough diagnostic work-up is needed. This work-up preferably includes video capsule enteroscopy (VCE), double-balloon enteroscopy (DBE), computed tomography (CT) combined with 18F-fluorodeoxyglucose positron emission tomography scan (18F-FDG-PET scan) if possible and magnetic resonance enteroclysis (MRE). Nowadays, most EATL patients are treated with chemotherapy mostly preceded by resection of the tumour and followed by stem cell transplantation. Despite these therapies outcome of EATL remains very poor with a 5-year survival of 8-20%. In order to improve survival prospective multicentre trials, studying new therapies are needed. The combination of chemotherapy, monoclonal antibodies and/or apoptosis inducing small molecules might be a potential treatment for EATL in the (nearby) future.

Incidence of enteropathy--associated T-cell lymphoma: a nation-wide study of a population-based registry in The Netherlands.

OBJECTIVE: Enteropathy-associated T-cell lymphomas (EATLs) are T-cell non-Hodgkin lymphomas of the small bowel, which are specifically associated with coeliac disease (CD). To our knowledge no studies have previously reported on the overall incidence of EATLs in the general population. The aim of this study was to investigate the incidence of EATL and the demographic characteristics of patients with EATL in The Netherlands. MATERIAL AND METHODS: A survey of the nation-wide network and registry of histo- and cytopathology reports in The Netherlands (PALGA) was performed. We included all T-cell lymphomas detected between January 2000 and December 2006 that initially presented in the small bowel. Crude and world standardized incidence rates were computed as well as gender- and age-specific incidence rates. Finally, the distribution of characteristics such as the localization, the Marsh classification and method of diagnosis are described. RESULTS: Clinicopathological data were gathered for 116 cases of EATL. The mean age at primary presentation of EATL was 64 years. The crude incidence in the total Dutch population was 0.10/100,000 with an incidence of 2.08/100,000 in the over 50-year-olds. Age-specific incidences were 1.44/100,000 in the 50-59 years age group, 2.92/100,000 in the 60-69 years age group, and 2.53/100,000 in the 70-79 years age group. There was a significant predominance of males (64%, p=0.004, CI 54-72); above the age of 50 the gender-specific incidence was 2.95/100,000 in males versus 1.09/100,000 in females. Most EATLs were localized in the proximal small intestine and the diagnosis was made by surgical resection in the majority of cases. CONCLUSIONS: EATL is a rare disease with an incidence of 0.10 per 100,000 inhabitants per year, occurring in older age, with a peak incidence in the 7th decade. The tumour is mainly localized in the proximal small intestine. Although uncomplicated CD is twice as frequent in female patients, EATL is more prevalent in males.

Calcium homeostasis during magnesium treatment in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Magnesium treatment in patients with subarachnoid hemorrhage (SAH) can result in hypocalcemia; this hypocalcemia increases the risk of delayed cerebral ischemia (DCI) and poor outcome. We assessed whether low serum levels of total calcium in patients with SAH treated with magnesium is mediated by parathyroid hormone (PTH) or calcitriol, and whether increased PTH or low serum levels of ionized calcium are associated with an increased risk of DCI and poor outcome. PATIENTS AND METHODS: We studied 167 patients included in a randomized, placebo controlled trial on magnesium in SAH. Mean serum magnesium during treatment was related to mean serum levels of ionized calcium, PTH and calcitriol with linear regression. Hypocalcemia (Ca(2+)) and high serum PTH were related to the occurrence of DCI by means of the Cox proportional hazards model and to poor outcome by logistic regression. RESULTS: Serum magnesium was inversely related to ionized calcium (B = -0.1; 95% CI -0.12 to -0.06), but not to PTH or calcitriol. Neither hypocalcemia nor high serum PTH was related to DCI. Hypocalcemia did not increased the risk for poor outcome (OR 1.2; 95% CI 0.6-2.3). In the subgroup of patients with known PTH (n = 67), high serum PTH increased the risk for poor outcome (OR 5.4; 1.6-18.9). CONCLUSIONS: Magnesium treatment in patients with SAH leads to hypocalcemia without effect on outcome. PTH is related to poor outcome, but this is independent of magnesium therapy.

Hypocalcaemia may reduce the beneficial effect of magnesium treatment in aneurysmal subarachnoid haemorrhage.

To assess whether magnesium treatment in patients with subarachnoid haemorrhage (SAH) is associated with hypocalcaemia and whether hypocalcaemia in these patients is associated with an increased risk of delayed cerebral ischemia (DCI) and poor outcome. All 137 patients randomized in the clinically controlled "Magnesium in Aneurysmal Subarachnoid Haemorrhage" trial were included. The relationship between mean serum magnesium and mean serum calcium during treatment was assessed with linear regression. The relationship between hypocalcaemia (serum calcium < 2.0 mmol/L) during treatment and the occurrence of DCI and poor outcome was studied with the Cox proportional hazards method and logistic regression, respectively. There was a statistically significant inverse relation between elevated serum magnesium and hypocalcaemia (B = -0.27; 95% CI, -0.33 to -0.20; p < 0.001). Patients with hypocalcaemia during study treatment had an increased frequency of DCI (HR 2.1; 95% CI, 1.0 to 4.3), and an increased risk for poor outcome (OR 2.9; 95% CI, 1.4 to 6.4), but this effect attenuated in the multivariable analysis (OR 1.9; 95% CI, 0.8 to 4.7). In conclusion, prolonged elevated serum magnesium is associated with hypocalcaemia. Hypocalcaemia is associated with an increased risk of DCI and poor outcome and may therefore reduce the potential beneficial effect of magnesium treatment in SAH.