Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia.

Arsenic trioxide (ATO) is highly effective in acute promyelocytic leukemia (APL), but despite its multiple mechanism of action, it has no activity in acute myeloid leukemia (AML) that excludes APL (non-APL AML). Ascorbic acid (AA) and ATO induces apoptosis in AML cell lines by depleting intracellular glutathione and generation of reactive oxygen species. In this study, we evaluated the effect of ATO plus AA in patients with non-APL AML. The study enrolled patient aged 18 or older with relapsed or refractory AML (non-APL) after conventional chemotherapy or previously untreated patients 55 years or older who were unfit for standard induction chemotherapy for AML. Intravenous ATO (0.25 mg/kg/day over 1-4 h) was given with intravenous AA (1 g/day over 30 min after ATO) for 5 days a week for 5 weeks (25 doses). Eleven AML patients were enrolled, including six previously untreated elderly patients aged 66-84 years in whom five had antecedent hematological disorder (ADH). Among 10 evaluable patients, one achieved a CR one a CRi and 4 patients had disappearance of blasts from peripheral blood and bone marrow. Five of the six responders were seen in previously untreated elderly patients. ATO related toxicity was mild. The combination of ATO and AA has limited clinical meaningful antileukemia activity in patients with non-APL AML.

Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia.

PURPOSE: Asparaginase treatment is standard in all pediatric acute lymphoblastic leukemia (ALL) regimens, whereas in adults, it is either excluded or administered for a shorter duration. Several adult ALL protocols are adapting pediatric regimens, but the optimal implementation of asparaginase is not well studied, considering its potential higher toxicity. We studied a pegaspargase dosing strategy based on its pharmacokinetic characteristics in adults. PATIENTS AND METHODS: Between 2004 and 2009, 51 adults age 18 to 57 years with newly diagnosed ALL were treated with a regimen adapted from a pediatric trial that included six doses of intravenous pegaspargase at 2,000 IU/m(2) per dose. Intervals between doses were longer than 4 weeks and rationally synchronized with other chemotherapy drugs to prevent overlapping toxicities. Pegaspargase was administered with steroids to reduce hypersensitivity. Asparaginase-related toxicities were monitored after 173 pegaspargase doses. RESULTS: The most common grade 3/4 asparaginase-related toxicities were lengthy hyperbilirubinemia and transaminitis, occasionally resulting in subsequent treatment delays. All toxicities resolved spontaneously. Forty-five percent of patients were able to receive all six doses of pegaspargase, and 61% received ≥ three doses. In only 20% of patients, the drug was discontinued after pegaspargase-related serious toxicity. Ninety-six percent achieved complete remission, almost all within 4 weeks, and a low induction death rate was seen. Seven-year disease-free and overall survival were 58% and 51%, respectively. CONCLUSION: Our dose and schedule of pegaspargase, based on its pharmacokinetics, and our detailed toxicity profile could be applied for safer adaptation of pediatric ALL protocols in adults.

Single port laparoscopic cholecystectomy with the TriPort system: a case report.

Single port access surgery may be the next generation of minimally invasive surgery. This study reports a recent experience with the TriPort system (trademark pending, Advanced Surgical Concepts, Wicklow, Ireland) to perform a laparoscopic cholecystectomy via a single peri-umbilical incision. To the authors' knowledge, this is one of the first cases of single port laparoscopic cholecystectomy ever performed with this device in the United States. Randomized studies to compare single port laparoscopic cholecystectomy with traditional laparoscopic cholecystectomy, with specific regard to postoperative pain scores, would be helpful in determining how much additional benefit, if any, there is to the patient.

Prosthetic material in inguinal hernia repair: how do I choose?

With numerous prosthetic options and a changing landscape of prosthetic development, a systematic approach to choosing a prosthetic is more sensible than trying to memorize all the details of each prosthetic. The surgeon should hone a single technique for the vast majority of inguinal hernia repairs to maximize proficiency. This limits the number of prosthetics to those suitable for that technique. Narrowing the choice further should be based on the likelihood that a given prosthetic will achieve the preoperative goals of the hernia repair. For alternative clinical scenarios, the surgeon should know one to two additional techniques, which may require a different prosthetic. The surgeon should use existing experimental and clinical data to estimate long-term benefits of any new prosthetic.

Comparison of patient-centered outcomes after laparoscopic Nissen fundoplication for gastroesophageal reflux disease or paraesophageal hernia.

BACKGROUND: Patients undergoing laparoscopic Nissen fundoplication (LNF) with paraesophageal hernias (PEH) are not only older and less healthy than those with gastroesophageal reflux disease (GERD), but in addition the repair is more complicated. We evaluated whether outcomes relating to GERD symptoms and quality of life (QOL) were impacted by the presence of PEH. METHODS: Prospectively entered data from 149 patients (109 GERD and 40 PEH) were evaluated prior to and one year after LNF with standardized and validated symptoms scores. Scores for heartburn, dysphagia, disease-specific QOL (GERD-HRQL), and general health-related QOL (SF-12 physical and mental component scores) were compared between patients undergoing LNF for PEH or for GERD alone, at baseline and one year after surgery. p < 0.05 was considered statistically significant. RESULTS: Preoperative data for GERD-HRQL, heartburn, and dysphagia were available for 134 patients, with 96% one-year follow-up. SF-12 data were collected for 98 patients with 100% follow-up. PEH patients were older and had greater comorbidity. Preoperative GERD-HRQL and heartburn were significantly worse in the GERD group. One year after surgery, both GERD and PEH patients showed significant improvement in GERD-HRQL, heartburn and dysphagia scores, with no difference in any of these disease or symptom measures between the two study groups. Postoperative PCS and MCS scores showed improvement in GERD patients, while PEH patient scores remained at or below the population mean. CONCLUSIONS: LNF is equally effective as an antireflux procedure in both GERD and PEH patients, prevents symptoms of reflux in PEH patients that have none preoperatively, and does not increase dysphagia in either group. Despite the increased complexity of the procedure, LNF provides an effective control of reflux symptoms in patients undergoing PEH repair.

Unsuspected pulmonary emboli in cancer patients: clinical correlates and relevance.

PURPOSE: Advances in computed tomography (CT) scanning have led to the detection of unsuspected pulmonary emboli (PE) on routine cancer staging scans. We hypothesized that these patients had signs or symptoms suggestive of PE that may have been overlooked by their health care providers. PATIENTS AND METHODS: A retrospective chart review was performed on 59 patients found on routine cancer staging CT scans to have unsuspected PE. Information on patient demographics, malignancy characteristics, risk factors for venous thromboembolism (VTE), and symptoms was recorded. A retrospective case-control analysis was then performed using two age- and stage-matched control patients for each patient who had similar staging CT scans performed during the same period. RESULTS: Fifty-two patients with unsuspected PE were identified. Forty-four percent had signs or symptoms commonly associated with PE; when fatigue was included, 75% were symptomatic. Ninety-two control patients were identified for 46 of the case patients. Patients with unsuspected PE were significantly more likely to have had a prior history of VTE (20% v 3%; P = .007). The patients with PE were significantly more likely than control patients to complain of fatigue (54% v 20%; P = .0002) and shortness of breath (22% v 8%; P = .02). There was no difference between the groups in administration of chemotherapy within 30 days, central venous catheter use, or erythropoietin therapy. CONCLUSION: Seventy-five percent of patients found to have unsuspected PE on cancer staging CT scans were symptomatic. Fatigue and shortness of breath were significantly more common in patients with unsuspected PE than in control patients.

Inhibition of nitric oxide synthase reduces renal ischemia/reperfusion injury.

BACKGROUND: The role of nitric oxide (NO) production because of inducible nitric oxide synthase (iNOS) in the pathogenesis of renal ischemia/reperfusion (I/R) injury is unclear. In this study the roles of both iNOS and NO were characterized in a rat model of renal I/R injury. In addition, the effect of iNOS inhibition on renal function was evaluated. METHODS: Sprague-Dawley rats underwent 45 min of left renal ischemia and contralateral nephrectomy followed by various periods of reperfusion and renal function analysis [plasma creatinine, fractional excretion of sodium (FENa), creatinine clearance (CrCl), and measurement of plasma and urine NO levels]. In addition, the effect of treatment with 1400W, a highly selective iNOS inhibitor, was evaluated. RESULTS: Renal dysfunction peaked at 48 h after reperfusion and immunohistochemistry studies revealed iNOS expression in the vasculature (3 h) and renal tubules (48 h) after reperfusion. Renal function improved significantly in treated animals compared to controls [creatinine of 1.1 v. 1.9 mg/dl (P < 0.05) and CrCl of 0.54 v. 0.31 ml/min (P < 0.05), respectively]. In addition, FENa was decreased by 50%, plasma NO levels were significantly lower (32.7 v. 45.7 micromol/L, P < 0.01), and deposition of nitrotyosine in the tubules of treated rats was less than in control animals. CONCLUSIONS: These data support the hypothesis that iNOS and NO are involved in the pathogenesis of renal I/R injury and suggests that use of iNOS inhibitors may be a valuable therapeutic strategy clinical situations where renal I/R may be prevalent.