Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial.

AIM: To determine equivalence of modified gemcitabine and oxaliplatin compared with gemcitabine and cisplatin in unresectable gallbladder cancer (GBC). Primary end-point was overall survival (OS). METHODS: Open label, prospective, randomised phase III equivalence study. Inclusion criteria included histologically proven unresectable GBC, 18 years or older, adequate organ functions and Eastern Cooperative Oncology Group ≤2. SAMPLE SIZE: 108 patients were required in each arm to have an equivalence margin of ±2 months with power of 80%. TREATMENT: Modified gemcitabine and oxaliplatin (mGemOx)-gemcitabine 900 mg/m2, oxaliplatin 80 mg/m2, maximum 6 cycles; gemcitabine + cisplatin (CisGem)-gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, maximum 8 cycles, all day 1 and 8 every 3 weeks. RESULTS: Two hundred sixty subjects were recruited between February 2011 and July 2015. Two hundred forty-three patients (119, mGemOx and 124, CisGem) received at least 1 dose and analysed for safety and efficacy (modified intention to treat). Median OS was 8·5 months for whole group (95% confidence interval [CI]: 7·9-9·1). Median OS in mGemOx was 9 months and 8·3 months in CisGem; p = 0·057 (hazard ratio = 0·78; 95% CI = 0·60-1·02). Restricted mean OS for follow-up limited to 30 months was 11·2 months (95% CI: 9·8-12·6) in mGemOx and 10·4 months (95% CI: 9·1-11·7) in CisGem. Difference of the mean was 0·8 months with 95% CI, exceeding 2 months (-1·1 to 2·7), hence rejecting equivalence. Peripheral neuropathy, thrombocytopaenia in mGemOx and nephrotoxicity was higher with CisGem. CONCLUSION: This trial failed to show equivalence of eight cycles of CisGem to six cycles of mGemOx. Numerically OS was better with mGemOx. Toxicities were different. The trial was not powered to answer superiority. CLINICAL TRIAL REGISTRATION: CTRI/2010/091/001406.

Community-acquired urinary tract infections due to extended-spectrum ß -lactamase-producing organisms in United Arab Emirates.

BACKGROUND: The epidemiology of extended-spectrum ß-lactamase (ESBL)-producing bacteria is fast evolving with increasing global trend towards community-acquired infections. Limited information available about ESBLs therapy outcomes and control strategies, especially in the Middle Eastern countries. METHODS: We studied 399 ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates from urinary tract infections (UTIs) occurred between 2014 and 2016 in University Hospital Sharjah. We included 124 ESBL-negative E. coli and K. pneumoniae isolates from UTIs as controls. Pearson Chi squares test and independent t-test were used to compare difference between ESBL positives and negatives. Multivariate logistic regression analysis was also performed. RESULTS: Approximately 75% of the E. coli and K. pneumoniae isolates causing UTIs were community-acquired. We found that recurrent UTIs, old age, and catheterization among other risk factors for community-acquired ESBL-positive UTIs. Majority of these ESBL-positive isolates were resistant to antibiotics such as ciprofloxacin (74%) and trimethoprim-sulphamethoxazole (73%) that are commonly used for treatment of community-acquired urinary tract infections. CONCLUSIONS: ESBL-producing E. coli and K. pneumoniae have become major etiological pathogens of community-acquired UTIs in the United Arab Emirates. Healthcare providers should implement better infection control strategies and careful use of antimicrobials especially in out-patient and community settings.

Chronic intestinal pseudo-obstruction: systematic histopathological approach can clinch vital clues.

The histopathological approach of chronic intestinal pseudo-obstruction (CIP) is critical, and the findings are often missed by the histopathologists for lack of awareness and nonavailability of standard criteria. We aimed to describe a detailed histopathological approach for working-up cases of CIP by citing our experience. Eight suspected cases of CIP were included in the study to determine and describe an approach for reaching the histopathological diagnosis collected over a period of the last 1.5 years. The Hirschsprung's disease was put apart from the scope of this study. A detailed light microscopic analysis was performed along with special and immunohistochemical stains. Transmission electron microscopy was carried out on tissue retrieved from paraffin embedded tissue blocks. Among the eight cases, three were neonates, one in the pediatric age group, two adolescent, and two adults. After following the described critical approach, we achieved the histological diagnoses in all the cases. The causes of CIP noted were primary intestinal neuronal dysplasia (IND) type B (in 4), mesenchymopathy (in 2), lymphocytic myenteric ganglionitis (in 1), and duplication of myenteric plexus with leiomyopathy (in 1). Desmosis was noted in all of them along with other primary pathologies. One of the IND patients also had visceral myopathy, type IV. Histopathologists need to follow a systematic approach comprising of diligent histological examination and use of immunohistochemistry, immunocytochemistry, and electron microscopy in CIP workup. Therapy and prognosis vary depending on lesions identified by pathologists. These lesions can be seen in isolation or in combinations.