Association of Interleukin-1B and Interleukin-4 Gene Variants with Autoimmune Thyroid Diseases in Tunisian Population

Autoimmune thyroid diseases (AITD) including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are complex genetic diseases. Cytokines IL-1B and IL-4 play a role in the pathogenesis of AITD. This study was conducted on Tunisian patients with GD or HT to investigate the association of IL-1B and IL-4 gene polymorphisms with the risk and the prognosis of AITD. A total of 358 healthy controls and 341 patients with AITDs (249 HT and 92 GD) were genotyped for IL-1B+3953C/T and IL-4 intron 3 VNTR polymorphisms. A significant association was found between IL-1B+3953C/T polymorphism and GD or HT, both in the dominant and additive models. The IL-1B+3953T allele was associated with GD (p = 0.0003, OR = 1.93, CI = 1.34-2.78) and HT (p = 0.009, OR = 1.43, CI = 1.09-1.88). The IL-4 VNTR polymorphism was associated only with HT risk both in additive (p = 0.03, OR = 0.31, CI = 0.11-0.86) and recessive (p = 0.03, OR = 3.04, CI = 1.13-8.17) models. No significant association was found between IL-1B+3953C/T polymorphism and change in the serum concentrations of TSH and FT4 in GD and HT patients. In HT patients, the IL-1B+3953T allele (p = 0.009, OR = 0.42, CI = 0.22-0.83) and the IL-1B+3953T/T genotype (p = 0.03, OR = 0.21, CI = 0.04-1.07) were more frequent in the absence than in the presence of an anti-TPO antibody. The proportion of HT patients with the P1P2 genotype of the IL-4 gene was significantly higher in the absence than in the presence of the anti-TPO antibody (p = 0.04, OR = 0.39, CI = 0.17-0.89). These preliminary results suggest that IL-1B and IL-4 gene polymorphisms may be associated with GD and HT susceptibility and may represent prognostic factors for predicting the severity of HT.     

Health‐related quality of life of patients with advanced breast cancer treated with everolimus plus exemestane versus placebo plus exemestane in the phase 3, randomized,controlled, BOLERO‐2 trial

BACKGROUND:

The randomized, controlled BOLERO‐2 (Breast Cancer Trials of Oral Everolimus) trial demonstrated significantly improved progression‐free survival with the use of everolimus plus exemestane (EVE + EXE) versus placebo plus exemestane (PBO + EXE) in patients with advanced breast cancer who developed disease progression after treatment with nonsteroidal aromatase inhibitors. This analysis investigated the treatment effects on health‐related quality of life (HRQOL).

METHODS:

Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30) questionnaire, HRQOL was assessed at baseline and every 6 weeks thereafter until disease progression and/or treatment discontinuation. The 30 items in 15 subscales of the QLQ‐C30 include global health status wherein higher scores (range, 0‐100) indicate better HRQOL. This analysis included a protocol‐specified time to definitive deterioration (TDD) analysis at a 5% decrease in HRQOL versus baseline, with no subsequent increase above this threshold. The authors report additional sensitivity analyses using 10‐point minimal important difference decreases in the global health status score versus baseline. Treatment arms were compared using the stratified log‐rank test and Cox proportional hazards model adjusted for trial stratum (visceral metastases, previous hormone sensitivity), age, sex, race, baseline global health status score and Eastern Cooperative Oncology Group performance status, prognostic risk factors, and treatment history.

RESULTS:

Baseline global health status scores were found to be similar between treatment groups (64.7 vs 65.3). The median TDD in HRQOL was 8.3 months with EVE + EXE versus 5.8 months with PBO + EXE (hazard ratio, 0.74; P = .0084). At the 10‐point minimal important difference, the median TDD with EVE + EXE was 11.7 months versus 8.4 months with PBO + EXE (hazard ratio, 0.80; P = .1017).

CONCLUSIONS:

In patients with advanced breast cancer who develop disease progression after treatment with nonsteroidal aromatase inhibitors, EVE + EXE was associated with a longer TDD in global HRQOL versus PBO + EXE. Cancer 2013. © 2013 American Cancer Society.     

Klatskin tumor presenting as unresectable perihilar hepatic mass: A case report

Cholangiocarcinoma is a rare liver tumor with three types: intrahepatic, extrahepatic, and perihilar, which alone account for about 50% of cases. The diagnosis is late with a poor prognosis. Imaging through Bili MRI and CT scan plays an essential role in the classification and staging of tumors for therapeutic management. We report the case of a 62-year-old woman, received for cholestasis syndrome and weight loss in whom CT and MRI found a hepatic hilar mass. The diagnosis of Klatskin''s tumor was retained with a histological finding of adenocarcinoma. The patient underwent biliary drainage and palliative treatment as the tumor was unresectable.     

Absorption,distribution, metabolism,and excretion (ADME) of <Superscript>14</Superscript>C-sonidegib (LDE225) in healthy volunteers

Purpose

The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects.

Methods

Six subjects received a single oral dose of 800 mg ¹⁴C-sonidegib (74 kBq, 2.0 µCi) under fasting conditions. Blood, plasma, urine, and fecal samples were collected predose, postdose in-house (days 1–22), and during 24-h visits (weekly, days 29–43; biweekly, days 57–99). Radioactivity was determined in all samples using accelerator mass spectrometry (AMS). Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to determine concentrations of sonidegib and its main circulating metabolite in plasma. Metabolite profiles and structures were determined in pooled plasma, urine, and fecal samples using high-performance LC–AMS and LC–MS/MS, respectively.

Results

A single dose of ¹⁴C-sonidegib was well tolerated in healthy subjects. Unchanged sonidegib and total radioactivity reached peak concentration in plasma by 2 and 3 h, respectively, and demonstrated similarly long half-lives of 319 and 331 h, respectively. Absorbed sonidegib (estimated 6–7 %) was extensively distributed, and the approximate terminal volume of distribution was 2,500 L. Unchanged sonidegib and a metabolite resulting from amide hydrolysis were the major circulating components (36.4 and 15.4 % of radioactivity area under the curve, respectively). Absorbed sonidegib was eliminated predominantly through oxidative metabolism of the morpholine part and amide hydrolysis. Unabsorbed sonidegib was excreted through the feces. Metabolites in excreta accounted for 4.49 % of the dose (1.20 % in urine, 3.29 % in feces). The recovery of radioactivity in urine and feces was essentially complete (95.3 ± 1.93 % of the dose in five subjects; 56.9 % of the dose in one subject with incomplete feces collection suspected).

Conclusions

Sonidegib exhibited low absorption, was extensively distributed, and was slowly metabolized. Elimination of absorbed sonidegib occurred largely by oxidative and hydrolytic metabolism.

     

An unusual cause of peritonitis: Perforation of a gastric carcinoma

Gastric carcinoma perforation is an uncommon consequence that is often missed during the preoperative stage. Perforation may occur at any stage of cancer, but it is more common in late stages. It can also happen early in the illness. Because of the spilled stomach contents, it produces an acute abdominal syndrome. The goal of treatment should be to strike a balance between the emergency situation of peritonitis and oncological surgical techniques. A case of stomach cancer perforation with typical imaging findings is presented.     

Peritoneal thickening: It's not always carcinomatosis

The peritoneal pseudotumor localization of tuberculosis is a rare clinical form, representing 1 to 3% of extrapulmonary site of tuberculosis. It represents the sixth most common extra pulmonary site of tuberculosis. It is a great mimicker with major overlapping clinical and imaging features. Differentiating peritoneal tuberculosis and peritoneal carcinomatosis in imaging remains challenging. We present a case of a 37-year old woman complaining of chronic abdominal pain and distension who has been diagnosed to have peritoneal carcinomatosis based on CT findings, histopathological study then revealed necrotizing, granulomatous inflammation consistent with tuberculosis. This case showed the interest to be aware of the common and uncommon imaging features of tuberculosis by radiologists to better assess for alternative differential diagnosis.