Results of Laparoscopic Cholecystectomy in Acute Cholecystitis in Diabetic Patients: A Study with 50 Cases.

Acute cholecystitis (AC) is a common surgical condition requiring emergency hospitalization. Diabetic patient with gall stones disease is more prone to develop acute cholecystitis and its complications e.g. mucocele, empyema, gangrene and perforation. Early laparoscopic cholecystectomy (ELC) has proved to be an effective and safe day case surgical procedure for AC and their complications. This cross sectional study of diabetic patients admitted with acute cholecystitis, at the Department of Surgery of Bangladesh Institute of Researcher of Rehabilitation in Diabetes, Endocrine and Metabolic Disorder (BIRDEM) General Hospital, Dhaka, Bangladesh from March 2016 to January 2017. A total number of 50 patients of known diabetes of acute cholecystitis were recruited irrespective of their age and sex and by excluding pregnant woman, obstructed jaundice and severe cardiopulmonary disease. More than half (52.0%) of the cholecystitis patients belonged to 31-40 years with mean age was 52.5±12.1 years. Females were predominant in this study (68.0%) with male: female ratio was 1:2.1. All (100%) patents had pain in right hypochondrium but relatively lower than non-diabetic patient due to diabetic neuropathy followed by majority 74.0% had nausea/vomiting, 70.0% had history of flatulence and dyspepsia, 62.0% had Murphy's sign positive. Thirty (60.0%) patients had glycaemic control and 20(40.0%) had uncontrolled DM. Insulin received patients were 35(70.0%) and 15 took oral hypoglycemic drug. Regarding postoperative complication, 8.0% had severe vomiting, right hypochondriac pain, 4.0% had wound sepsis and 2.0% had decreased pulmonary function and mild chest infection. In this study among laparoscopic finding during operation age and sex were not statistically significant. There was no mortality; laparoscopic cholecystectomy is the safe, accepted and preferred method of treatment for acute cholecystitis.

An Overview of Unsafe Abortion: Patterns and Outcomes in a Tertiary Level Hospital.

Unsafe abortion is one of the most critical global public health concerns and human rights challenges of the current time. The complications arising from unsafe abortion account for the death of almost 192 women each day; that is one woman every eight minutes and nearly all of them in developing countries. It is a descriptive type of observational study where all abortion related admissions from July 2017 to June 2018 in Obstetrics & Gynaecology department of Mymensingh Medical College Hospital were analyzed. Cases of unsafe abortion were identified as missed abortion, incomplete abortion and septic abortion. Total 2396 abortion related cases were admitted in one year. Among them 2173 cases were unsafe abortion (90.69%). The commonest mode of unsafe abortion was by taking improper regimen of different types of oral abortifacients either by self-administration or by improper prescriptions of local medical dispensers in 90% women. The commonest clinical presentation was per vaginal moderate to heavy bleeding in 88.5% women. After evaluation, the commonest diagnosis made was incomplete abortion in 92.87% women. The first line of intervention taken was recommended dose of medications like Misoprostol alone or Misoprostol followed by Mifepristone in 96.3% women to avoid unnecessary endometrial injury by surgical procedure. Further 44.2% women underwent Manual Vacuum Aspiration and thus reducing hospital stay to around 3.0±0.25 days. Almost all the patients (94%) were given post abortion contraceptives along with long acting family planning services to 20% patients. The miserable complication was septic abortion in 1.29% women and they were mainly done by insertion of foreign bodies which contribute to total 4.4% of maternal death. The impact of unsafe abortion on the woman and her family is intimidating. Timely and proper management of unsafe abortions and their complications with adequate provision for post abortion care may reduce the morbidity and mortality related to it. Moreover, use of long acting contraceptives to prevent unintended pregnancy and access to safe abortion may reduce the burden of unsafe abortions on public health system.

A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma.

BACKGROUND: Treatment options for sarcoma are limited. Histone deacetylase inhibitors increase the efficacy of topoisomerase II inhibitors by promoting access to chromatin and by down-regulating DNA repair. Thus, combined panobinostat and epirubicin therapy was evaluated to treat refractory sarcoma. PATIENTS AND METHODS: Patients with advanced solid tumors were enrolled in a 3 + 3 dose-escalation phase I trial of panobinostat given on days 1, 3, and 5 followed by 75 mg/m(2) of epirubicin on day 5 in 21-day cycles, with a dose expansion at maximum tolerated dose (MTD) in 20 sarcoma patients. Peripheral blood mononucleocyte histone acetylation was also evaluated. RESULTS: Forty patients received 20-60 mg panobinostat. Dose-limiting toxicities included thrombocytopenia, febrile neutropenia, and fatigue at 60 mg, defining a panobinostat MTD at 50 mg. Four responses were seen in 37 assessable patients, all after progression on prior topoisomerase II inhibitors. For those with sarcoma, 12 of 20 derived clinical benefit (1 partial response and 11 stable disease, median overall survival 8.3 months), including 8 of 14 previously progressed on topoisomerase II therapy. Treatment benefits correlated with increased histone acetylation and decreased neutrophil count on day 5. CONCLUSIONS: Panobinostat and epirubicin treatment is well tolerated and may reverse anthracycline resistance. Changes in histone acetylation and associated decrease in neutrophil count correlated with clinical benefit and warrant investigation as predictive biomarkers. CLINICAL TRIAL: This trial is registered at www.Clinicaltrials.gov, Identifier: NCT00878904.

Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX vaccine in advanced-stage non-small-cell lung cancer.

Tumor vaccines composed of autologous tumor cells genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) (GVAX) have demonstrated clinical activity in advanced-stage non-small-cell lung cancer (NSCLC). In an effort to remove the requirement for genetic transduction of individual tumors, we developed a 'bystander' GVAX platform composed of autologous tumor cells mixed with an allogeneic GM-CSF-secreting cell line. We conducted a phase I/II trial of this vaccine (3-12 biweekly vaccinations) in advanced-stage NSCLC. Tumors were harvested from 86 patients, tumor cell processing was successful in 76, and 49 proceeded to vaccination. The most common toxicity was local vaccine injection site reactions. Serum GM-CSF pharmacokinetics were consistent with secretion of GM-CSF from vaccine cells for up to 4 days with associated transient leukocytosis confirming the bioactivity of vaccine-secreted GM-CSF. Evidence of vaccine-induced immune activation was demonstrated; however, objective tumor responses were not seen. Compared with autologous GVAX vaccines prepared by transduction of individual tumors with an adenoviral GM-CSF vector, vaccine GM-CSF secretion was approximately 25-fold higher with the bystander GVAX vaccine used in this trial. However, the frequency of vaccine site reactions, tumor response, time to disease progression, and survival were all less favorable in the current study.

Stage II (N1) lung cancer.

As therapies evolve and mature, the authors predict that the next 20 years will see significant advances in the understanding of non-small-cell lung cancer (NSCLC), in molecular stratification of NSCLC, and significant improvement in survival and cure rates. This survival will be achieved through early detection and combined treatments using effective surgical interventions, improved radiotherapeutics, and especially significantly enhanced, rationally designed systemic therapies.

Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: Phase I study.

Preclinical and in vitro studies have determined that copper is an important cofactor for angiogenesis. Tetrathiomolybdate (TM) was developed as an effective anticopper therapy for the initial treatment of Wilson's disease, an autosomal recessive disorder that leads to abnormal copper accumulation. Given the potency and uniqueness of the anticopper action of TM and its lack of toxicity, we hypothesized that TM would be a suitable agent to achieve and maintain mild copper deficiency to impair neovascularization in metastatic solid tumors. Following preclinical work that showed efficacy for this anticopper approach in mouse tumor models, we carried out a Phase I clinical trial in 18 patients with metastatic cancer who were enrolled at three dose levels of oral TM (90, 105, and 120 mg/day) administered in six divided doses with and in-between meals. Serum ceruloplasmin (Cp) was used as a surrogate marker for total body copper. Because anemia is the first clinical sign of copper deficiency, the goal of the study was to reduce Cp to 20% of baseline value without reducing hematocrit below 80% of baseline. Cp is a reliable and sensitive measure of copper status, and TM was nontoxic when Cp was reduced to 15-20% of baseline. The level III dose of TM (120 mg/ day) was effective in reaching the target Cp without added toxicity. TM-induced mild copper deficiency achieved stable disease in five of six patients who were copper deficient at the target range for at least 90 days.

Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264.

PURPOSE: To characterize the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of paclitaxel in patients with abnormal liver function. PATIENTS AND METHODS: Adults with tumors appropriate for paclitaxel therapy who had abnormal liver function tests were eligible. Patients were assigned to one of three treatment cohorts: I, AST level twofold normal and bilirubin level less than 1.5 mg/dL; II, bilirubin level 1.6 to 3.0 mg/dL; and III, bilirubin level greater than 3.0 mg/dL. Doses were explored in at least three patients within each cohort. Although designed to assess a 24-hour infusion schedule, the trial was extended to also assess a 3-hour regimen. Pharmacokinetics were to be studied in all patients. RESULTS: Eighty-one patients were assessable for toxicity. Patients with bilirubin levels greater than 1.5 mg/dL had substantial toxicity at all doses explored, whereas the toxicity for patients with elevated AST levels occurred at doses that ranged from 50 to 175 mg/m2 administered over 24 hours. In most patients, the DLT was myelosuppression. The pharmacokinetic data were insufficient to adequately evaluate the relationship between pharmacokinetics and toxicity in patients who received 24-hour infusions but provided evidence of a longer exposure to paclitaxel than anticipated for the doses used in this study in the 3-hour infusion group. CONCLUSION: If paclitaxel is used for patients with elevated levels of AST or bilirubin, dose reductions are necessary, and an increase in toxicity can be anticipated. The increased myelosuppression observed is at least partially because of altered paclitaxel pharmacokinetics in such patients.