Resection of pancreatic cystic neoplasms in recurrent acute pancreatitis prevents recurrent pancreatitis but does not identify more malignancies

BACKGROUNDRecurrent acute pancreatitis (RAP) may be a presenting feature of and an indication for resection of pancreatic cysts, including intra-ductal papillary mucinous neoplasm (IPMN). Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIMTo study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODSThis retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016. The prevalence of preoperative high-risk cyst features, and of neoplasia was compared between patients with and without RAP. To identify the cause of pancreatitis, all the patients had a detailed history of alcohol, smoking, medications obtained, and had cross-sectional imaging (contrast-enhanced computed tomography/magnetic resonance imaging) and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis. The incidence of RAP post-resection was the primary outcome.RESULTSIPMN accounted for 101 cases (58.7%) {[branch duct (BD) 59 (34.3%), main duct (MD) 42] (24.4%)}. Twenty-nine (16.9%) presented with RAP (mean 2.2 episodes): 15 had BD-IPMN, 8 MD-IPMN, 5 mucinous cystic neoplasm and 1 serous cystic neoplasm. Malignancy was similar among those with vs without RAP for all patients [6/29 (20.7%) vs 24/143 (16.8%)] and IPMN patients [6/23 (26.1%) vs 23/78 (29.5%)], although tended to be higher with RAP in BD-IPMN, [5/15 (33.3%) vs 3/44 (6.8%), P = 0.04]. At mean follow-up of 7.2 years, 1 (3.4%) RAP patient had post-resection RAP. The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02 (P < 0.0001). CONCLUSIONMalignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP. In addition, specific cyst charac-teristics were not clearly associated with RAP. The incidence of RAP was markedly decreased in almost all patients following cyst resection.     

Downregulation of GSTM2 enhances gemcitabine chemosensitivity of pancreatic cancer in vitro and in vivo

Glutathione-S-transferases (GSTs) not only show cytoprotective role and their involvement in the development of anticancer drug resistance, but also transmit signals that control cell proliferation and apoptosis. However, the role of GST isoforms in chemotherapy resistance remains elusive in pancreatic cancer. Here, we demonstrated that gemcitabine treatment increased the GSTM2 expression in pancreatic cancer cell lines. Knockdown of GSTM2 by siRNA elevated apoptosis and decreased viability of pancreatic cancer cells treated with gemcitabine. Moreover, in vivo experiments further showed that shRNA induced GSTM2 downregulation enhanced drug sensitivity of gemcitabine in orthotopic pancreatic tumor mice. We also found that GSTM2 levels were lower in tumor tissues than in non-tumor tissues and higher GSTM2 expression was significantly associated with longer overall survival. In conclusion, our findings indicate that GSTM2 expression is essential for the survival of pancreatic cancer cells undergoing gemcitabine treatment and leads to chemo resistance. Downregulation of GSTM2 in pancreatic cancer may benefit gemcitabine treatment. GSTM2 expression in patients also shows significant correlation with overall survival. Thus, our study suggests that GSTM2 is a potential target for chemotherapy optimization and prognostic biomarker of pancreatic cancer.     

A randomized prospective analysis of alteration of hemostatic function in patients receiving tranexamic acid and hydroxyethyl starch (130/0.4) undergoing off pump coronary artery bypass surgery

Postoperative hemorrhagic complications is still one of the major problems in cardiac surgeries. It may be caused by surgical issues, coagulopathy caused by the side effects of the intravenous fluids administered to produce plasma volume expansion such as hydroxyl ethyl starch (HES). In order to thwart this hemorrhagic issue, few agents are available. Fibrinolytic inhibitors like tranexamic acid (TA) may be effective modes to promote blood conservation; but the possible complications of thrombosis of coronary artery graft, precludes their generous use in coronary artery bypass graft surgery. The issue is a balance between agents that promote coagulation and those which oppose it. Therefore, in this study we have assessed the effects of concomitant use of HES and TA. Thromboelastogram (TEG) was used to assess the effect of the combination of HES and TA. With ethical committee approval and patient's consent, 100 consecutive patients were recruited for the study. Surgical and anesthetic techniques were standardized. Patients fulfilling our inclusion criteria were randomly allocated into 4 groups of 25 each. The patients in group A received 20 ml/kg of HES (130/0.4), 10 mg/kg of T.A over 30 minutes followed by infusion of 1 mg/kg/hr over the next 12 hrs. The patients in group B received Ringer's lactate + TA at same dose. The patients in the Group C received 20 ml/kg of HES. Group D patients received RL. Fluid therapy was goal directed. Total blood loss was assessed. Reaction time (r), α angle, maximum amplitude (MA) values of TEG were assessed at baseline, 12, 36 hrs. The possible perioperative myocardial infraction (MI) was assessed by electrocardiogram (ECG) and troponin T values at the baseline, postoperative day 1. Duration on ventilator, length of stay (LOS) in the intensive care unit (ICU) were also assessed. The demographical profile was similar among the groups. Use of HES increased blood loss significantly (P < 0.05). Concomitant use of TA reduced blood loss when used along with HES. r value was prolonged at 12 hours in all the groups and α angle was reduced at 12 hours in all the groups, where as MA value was reduced at 12 th hour in the HES group compared to the baseline and increased in TA + HES group. These findings were statistically significant. No significant change in Troponin T values/ECG, duration of ventilation and LOS ICU was observed. No adverse events was noticed in any of the four groups. HES (130/0.4) used at a dose of 20 ml/kg seems to produce coagulopathy causing increased blood loss perioperatively. Hemodilution produced by fluid therapy seems to produce Coagulopathy as observed by TEG parameters. Concomitant use of TA with HES appears to reverse these changes without causing any adverse effects in patients undergoing OPCAB surgery.     

Sulfated polysaccharide isolated from Ulva lactuca attenuates d-galactosamine induced DNA fragmentation and necrosis during liver damage in rats

Context: Ulva lactuca Linnaeus (Chlorophyceae), a commonly distributed seaweed, is rich in polysaccharide but has not been studied extensively.

Objective: The present study investigated the effects of crude fraction of Ulva lactuca polysaccharide (ULP) on d-galactosamine (d-Gal)-induced DNA damage, hepatic oxidative stress, and necrosis in rats.

Materials and methods: The rats were treated with ULP (100?mg/kg, orally) for 4 weeks before a single intraperitoneal injection of d-Gal (500?mg/kg). In addition to liver cell necrosis and DNA damage, antioxidant parameters, such as lipid peroxide (LPO), superoxide dismutase, and catalase, and histopathology of liver tissue were evaluated.

Results: ULP pre-treatment significantly attenuated a d-Gal-induced decrease in DNA and RNA levels (3.67?±?0.38) and (5.42?±?0.46), respectively. Comet tail length and acridine staining confirmed the number of cells undergoing necrosis were relatively lower in ULP treated rats (30?µm and 8–10% of counted cells) compared to rats treated with d-Gal (60?µm and 16% of counted cells). Biochemical (LPO, SOD and CAT) and histological evaluation (p?d-Gal-induced elevation of LPO and infiltration of inflammatory cells into liver tissue.

Discussion and conclusion: Although our previous studies have reported on the protective role of ULP against liver toxicity, our present findings show that ULP improved the hepatic antioxidant defense system against d-Gal-induced DNA damage and necrosis in rats.     

Hesperidin attenuates mitochondrial dysfunction during benzo(a)pyrene‐induced lung carcinogenesis in mice

The present study is designed to assess the mitochondrial status during benzo(a)pyrene (B(a)P)‐induced lung carcinogenesis in Swiss albino mice and to reveal the modulatory effect of hesperidin over it. B(a)P (50 mg/kg body weight)‐induced mitochondrial abnormalities was evident from alterations in mitochondrial lipid peroxides, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase, reduced glutathione, vitamin E, and vitamin C), major tricarboxylic acid (TCA) cycle enzyme activities (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha‐ketoglutarate dehydrogenase), electron transport chain (ETC) complexes activities and ATP levels. Ultrastructural changes in lung mitochondria were also in accord with the above aberrations. Hesperidin (25 mg/kg body weight) supplementation effectively counteracted all the above changes and restored cellular normalcy, indicating its protective role during B(a)P‐induced lung cancer.     

Synergistic effect of nicorandil and amlodipine on mitochondrial function during isoproterenol-induced myocardial infarction in rats

The synergistic effects of nicorandil (KATP-channel opener) and amlodipine (calcium-channel blocker) on heart mitochondrial enzymes and the mitochondrial antioxidant defence system was examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for two days showed significant changes in marker enzymes, mitochondrial enzymes and the mitochondrial defence system. Pre-co-treatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 days significantly prevented these alterations and restored enzyme activity to near normal. These findings demonstrate the protective and synergistic effect of nicorandil and amlodipine in combination against isoproterenol-induced cardiac damage.