Management of incidentally detected gallbladder carcinomas in a high prevalence area of gallbladder cancer.

BACKGROUND: There is an increasing incidence of advanced unresectable gallbladder cancer even in patients who undergo re-exploration and these cases are marked by poor survival even after undergoing curative resection and adjuvant chemotherapy. Lack of suspicion during primary surgery, unavailability of frozen section facilities and delayed referrals are believed to contribute to this high incidence. AIM: Our aim was to evaluate the results of re-surgery in incidental gallbladder cancers detected after open or laparoscopic cholecystectomy and to assess the outcome in patients who underwent complete radical cholecystectomy and adjuvant therapy. METHOD: We retrospectively analyzed the data from a prospectively maintained computerized database of all patients with incidentally detected gallbladder cancers operated in the Department of Surgical Oncology, from June 2006 to January 2013. RESULTS: Forty-two patients with incidental gallbladder cancer were re-explored. The median time of re-exploration after initial surgery was 65 days. Eighteen (43%) patients were found inoperable due to locally advanced unresectable or metastatic disease. Among the 24 (57%) patients who underwent completion radical cholecystectomy, 11 developed recurrence over a median time of 11 months. CONCLUSION: Despite the dismal prognosis, more than half of the incidentally detected gallbladder carcinoma patients could receive curative treatment. Identification of patients with incidentally discovered gallbladder cancer and early referral to an oncology center may ensure these patients receive curative resection thereby increasing their chances for long-term disease free survival.

A prospective, parallel group, open-labeled, comparative, multi-centric, active controlled study to evaluate the safety, tolerability and benefits of fixed dose combination of acarbose and metformin versus metformin alone in type 2 diabetes.

OBJECTIVE: The present study was a prospective, parallel group, open-labeled, comparative, multicentric, active controlled study to evaluate the safety, tolerability and benefits of fixed dose combination of acarbose and metformin versus metformin alone in type 2 diabetic patients. METHODS: A total of 229 patients with type 2 diabetes were enrolled at 5 medical centers across India. They received either acarbose (50 mg) + metformin (500 mg) bid/tid (n=115) or metformin monotherapy (500 mg) bid/ tid (n=114) for 12 weeks. Primary objective was to evaluate safety and tolerability based on the adverse events reported. Secondary objective was efficacy assessment based on changes in fasting, post prandial blood glucose and HbA1c values. RESULTS: In the acarbose + metformin group 10 patients reported 14 adverse events while in metformin group 9 patients reported 10 adverse events. No patient reported any serious adverse event or was withdraw from study because of adverse events. In the acarbose plus metformin group fasting blood glucose (FBG) decreased from a baseline of 158.85 +/- 18.14 mg/dl to 113.55 +/- 19.38 mg/dl (p < 0.0001) (decrease of 45.30 +/- 15.30 mg/dl) at 12 weeks, while in the metformin group fasting blood glucose decreased from a baseline of 158.31 +/- 26.53 mg/dl to 130.55 +/- 28.31 mg/dl (p < 0.0001) (decrease of 27.76 +/- 22.91 mg/dl) at 12 weeks. In the acarbose plus metformin group postprandial blood glucose (PPBG) decreased from a baseline of 264.65 +/- 34.03 mg/dl to 173.22 +/- 31.40 mg/dl (p < 0.0001) (decrease of 91.43 +/- 28.65 mg/dl) at 12 weeks, while in the metformin group PPBG decreased from a baseline of 253.56 +/- 36.28 mg/dl to 205.36 +/- 39.49 mg/dl (p < 0.0001) (decrease of 48.20 +/- 32.72 mg/dl) at 12 weeks. In the acarbose plus metformin group glycosylated haemoglobin (HbA1c) decreased from a baseline of 9.47 +/- 0.69% to 7.71 +/- 0.85% (p < 0.0001) (% decrease of 1.76 +/- 1.11) at 12 weeks, while in the metformin group HbAlc decreased from a baseline of 9.32 +/- 0.65% to 8.26 +/- 0.68% (p < 0.0001) (% decrease of 1.06 +/- 0.66) at 12 weeks. The combination of acarbose and metformin was found to be significantly superior in lowering the FBC (p < 0.0001), PPBG (p < 0.0001) and HbA1c (p < 0.0001) at 12 weeks as compared to metformin monotherapy. CONCLUSIONS: Fixed dose combination of acarbose and metformin was well tolerated and it was superior to metformin monotherapy in controlling FBG, PPBG and HbA(1C) levels in Type 2 Diabetes Mellitus patients.

Comparison of the efficacy, safety and tolerability of telmisartan with losartan in Indian patients with mild to moderate hypertension: a pilot study.

A prospective, randomised, double-blind, parallel group study was carried out to compare the efficacy, safety and tolerability of telmisartan 40 mg once daily with losartan 50 mg once daily in Indian patients with mild to moderate hypertension. It had a placebo run-in period of 2 weeks followed by drug treatment (telmisartan 40 mg, once daily or losartan 50 mg once daily) for 8 weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and safety was assessed by physical examination, laboratory parameters and evaluation of adverse events. Treatment with telmisartan resulted in a significant reduction of SBP of 10.3% and 13.7% as compared to 6.6% and 10.6% in losartan group at the end of 6th and 8th weeks respectively. At the end of 6th and 8th weeks, the reduction was 14.3% and 18.1% among telmisartan which was significantly more as compared to 8.8% and 14.3% in losartan group respectively. The laboratory values were within normal limits. Both drugs were well tolerated. Telmisartan monotherapy in a dose of 40 mg once daily has a clinically better therapeutic effect as compared to losartan 50 mg and a good tolerability profile in patients with mild to moderate hypertension.

Accelerated atherosclerosis.

The process of accelerated atherosclerosis appears to share common pathophysiologic mechanisms, namely, endothelial injury with early platelet involvement and subsequent progressive smooth muscle cell proliferation and thrombosis leading to vascular occlusion. Understanding the mechanisms of this process has made it possible to include strategies to limit vascular injury and reduce subsequent thrombotic and proliferating cellular responses. In contrast to spontaneous atherosclerosis, a more significant denuding endothelial injury appears to be the critical initiating event, followed by intense platelet involvement and thrombus formation, leading to an initial predominant process of smooth muscle cell proliferation in accelerated atherosclerosis. Risk factors like cigarette smoking and hypertension play an important role in this process. This accelerated proliferative process appears to be the cause of premature coronary occlusion in patients undergoing heart and kidney transplantation, coronary vein graft bypass and percutaneous transluminal coronary angioplasty and diabetes. This accounts for significant morbidity and mortality in these patients. Prophylactic anticalcinotic vasoprotection by suitable calcium antagonists may offer a more appropriate way of anti-arteriosclerotic arterial protection than the other procedures hitherto used. Calcium channel blockers have positive effects on a number of processes that may be associated with restenosis, including reduction of platelet aggregation, minimisation of vasospasm and inhibition of mitogens. In this article the role of nifedipine in accelerated atherosclerosis has been reviewed.

Efficacy and safety of the first parenteral selective COX-2 inhibitor, parecoxib sodium, in adult patients with postoperative pain.

Parecoxib, a prodrug of valdecoxib, a selective COX-2 inhibitor, has been recently introduced for the treatment of moderate to severe postoperative pain. This prospective, open, multicentric study enrolled 260 patients undergoing orthopaedic, gynaecological, dental and general surgery. Postoperatively, patients were treated with parecoxib, 40 mg IM/IV. There was a statistically significant decrease in the mean pain intensity score (p<0.05). At the end of 24 hours, 89.6% of total cases had a very good to total relief of pain. The mean duration of analgesia was 19.26 hours and mean time of onset of analgesia was 16.25 minutes ranging from 11-20 minutes. The laboratory values were within normal limits. The drug was well tolerated. There was no report of any hypersensitivity reaction. This study suggests that parecoxib, in a dose of 40 mg IM/IV, is an effective and safe option for the management of postoperative pain.