Clinical Gastroenterology Journal

Gastric cancer (also known as Stomach cancer) is an abnormal growth of cells that begins in the stomach. The stomach is a muscular sac located in the upper middle of your abdomen, just below your ribs. Stomach receives and holds the food we eat and then helps to break down and digest it. Gastric cancer can affect any part of the stomach.

Celiac Disease is autoimmune disorder occurring in genetically predisposed people. Celiac disease causes damage to the small intestine upon ingestion of Gluten. Gluten triggers immune response and damages villi lining found on the small intestine resulting in blocking the absorption of nutrients in small intestine. Symptoms associated with celiac disease are chronic diarrhea, abdominal distention, malabsorption and loss of appetite.

The first stage, the cephalic phase of digestion, begins with gastric secretions in response to the sight and smell of food. This stage includes the mechanical breakdown of food by chewing, and the chemical breakdown by digestive enzymes that take place in the mouth.

Aim: To evaluate the association and prognostic significance of P53 in gastric neoplasms with tumor site and its macroscopic appearance.
Methods: A total of 48 cases of endoscopic gastric biopsies and surgically resected specimens that include both pre-malignant and malignant neoplasms were collected. The following inclusion and exclusion criteria were adopted
Inclusion criteria: All gastric adenocarcinoma cases reported in both endoscopic biopsies as well as resected specimens, irrespective of age and sex were included for the study. Exclusion Criteria: Non-neoplastic lesions and benign tumors of stomach, Malignancies other than adenocarcinoma and gastrostomies performed for reasons other than gastric tumors were excluded from the study.
Results: GCs had a peak incidence in the age group of 51-60 years. The youngest age of presentation of gastric cancer was at 37 years in this study. 30 (62%) cases were reported in males and 18 (38%) cases were reported in females with male: female ratio accounting to 1.6:1. 25(52.08%) cases involved the pyloro-antrum, 12 (25%) involved body, 5 (10.42%) involved eso-cardia, 3 (6.25%) cases involved fundus and 3(6.25%) cases involved pan-gastric region. Ulcero-proliferative type(35%) was the most common gross appearance followed by ulcerative type(29%). P53 positivity was observed in 84% of tumors in pyloro-antrum, 83.2% of tumors in body, 40% of tumors in eso – cardia. 33.1% of tumors in fundus and 66.7% in pan – gastric tumors. The association with respect to site was found to be statistically significant with increased expression seen in tumors of pyloro-antrum. Among various gross types, P53 positivity was noted in 8 cases (57.8%) of ulcerative type, 9 cases (75%) of nodular type, 15 cases (88.2%) of ulcero-proliferative type and 3 cases (60%) of proliferative type. P53 expression showed statistically significant association with tumor location but not with macroscopic appearance. Conclusion: Identifying expression of P53 in GC could be helpful in categorizing patients eligible for targeted therapy. Patients at high risk of recurrence and poor survival can also be identified. A larger sample size and follow-up of these patients for 5 more years could throw more light on role of P53 mutation as long-term prognostic indicator.

Background: Saroglitazar, a novel Peroxisome Proliferator-Activated Receptor (PPAR) α/γ agonist, was evaluated in preclinical and clinical studies to evaluate its effectiveness in NASH.

Methods: Preclinical studies included: (a) Choline Deficient L-amino Acid-defined High Fat Diet (CDAHFD) murine NASH model; (b) Long Evans and Wistar rats model for hepatotropic activity; (c) DIAMOND™ NASH mice model. Clinical studies included: Phase 2 and Phase 3 studies in patients with biopsy proven NASH in India.

Results: In CDAHFD murine NASH model, Saroglitazar improved aspartate aminotransferase (AST), Alanine Aminotransferase (ALT) and prevented hepatocellular steatosis, hepatocyte ballooning and lobular inflammation. In Long Evans and Wistarrats model, Saroglitazar was found to be hepatotropic. In the DIAMOND™ NASH mice model, Saroglitazar showed a systemic effect with resolution of steatohepatitis and improvement in all the key histological features of NASH, dyslipidemia and insulin sensitivity. In the phase 2 study, Saroglitazar 4 mg significantly reduced ALT levels (U/L) from baseline (95.86 ± 37.65) to week 12 (44.37 ± 35.43). In the phase 3 study, there was a significantly higher proportion of patients with decrease in NAS ≥ 2 spread across at least 2 of the NAS components without worsening of fibrosis at week 52 in Saroglitazar 4 mg group (52.3%) compared to placebo group (23.5%) (p value-0.0427), achieving the primary efficacy endpoint. In the phase 3 study, there were no concerns with the safety profile of Saroglitazar.

Conclusion: Positive results from the preclinical and clinical studies provide evidence for the effectiveness of Saroglitazar in the treatment of NASH.