Efficacy and safety of first- or second-line irinotecan, cisplatin, and mitomycin in mesothelioma

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rapidly progressive lethal tumor. Treatment options remain limited and the outcome in recurrent disease is poor. METHODS: A Phase II open-label noncomparative study was conducted to assess the safety and efficacy of the triplet combination irinotecan, cisplatin, and mitomycin-C (IPM) chemotherapy in untreated patients and in those with previous exposure to chemotherapy. RESULTS: In 62 patients an objective response rate of 25% was observed. In the first-line setting progression-free survival measured 6.4 months (95% confidence interval [CI]: 4.5-7.3) and overall survival was 10.8 months (95% CI: 7.9-13.7). In the second-line setting progression-free survival was 7.3 months (95% CI: 3.4-11.2) and overall survival was also 7.3 months (95% CI: 4.8-9.8). Psychosocial well-being improved during chemotherapy and the main toxicity observed was neutropenia (40%). CONCLUSIONS: IPM appeared to have a reasonable response rate with an acceptable toxicity profile in the first- and second-line treatment of MPM.     

National inpatient complications and outcomes after surgery for spinal metastasis from 1993-2002

BACKGROUND: Information regarding patient outcomes, complications, and mortality after surgery for spinal metastasis has previously been derived from single-institution series. The aim of this study was to report inpatient mortality, complications, and outcomes on a national level. METHODS: The National Inpatient Sample (NIS) was utilized to identify 26,233 admissions of surgically managed spinal metastasis in the U.S. from 1993 through 2002. Multivariate analysis was performed to analyze the effects of patient and hospital characteristics on outcomes such as mortality, complications, discharge disposition, and length of stay. RESULTS: The in-hospital mortality rate was 5.6% and the complication rate was 21.9%. Pulmonary (6.7%) and postoperative hemorrhages or hematomas (5.9%) were the most common complications reported. A single postoperative complication increased the mean length of stay (LOS) by 7 days and the mortality rate by 11%. Multivariate analysis showed that complications were more likely in older patients and in patients with 2 or more comorbidities. With patients having no comorbidities as the reference group, 1 comorbidity increased the risk of in-hospital death by almost 4-fold. Mortality was significantly higher in men, in patients who had postoperative complications, and in patients who were operated in the earlier (1993-1997) year group. CONCLUSIONS: A national perspective is provided on inpatient complications and outcomes after surgery for spinal metastasis in the U.S. The significant negative effect of postoperative complications on mortality and resource utilization is demonstrated. Furthermore, preoperative comorbidity is identified as an important risk factor and its impact is defined on patient outcomes.     

Allopeptide-pulsed dendritic cells and composite tissue allograft survival

Composite tissue allografts (CTAs) contain their own reservoir of vascularized bone marrow, offering novel aspects for the induction of donor-specific tolerance. Additionally, the manipulation of recipient dendritic cells, pulsed with donor allopeptide, has been shown to engender solid organ allograft survival. To exploit these modalities, we have developed a protocol utilizing injection of recipient bone marrow-derived dendritic cells (BMDCs) pulsed with a donor-derived peptide for use in CTA transplantation. Six days prior to orthotopic hind-limb transplantation, Lewis rats received IV injection of donor allopeptide-pulsed, recipient BMDCs, in conjunction with a single dose of anti-lymphocyte serum. Control groups displayed signs of allograft rejection within 5 days postoperatively. Animals within the primary experimental cohort demonstrated prolongation of graft survival to an average of 8 days, and exhibited low numbers of donor T cells. The use of BMDCs in conjunction with transient immunosuppression has potential therapeutic application for induction of donor-antigen-specific tolerance to hind limb allografts.     

Strauch's technique for epigastric free flaps in rats revisited: a simple and effective method to increase patency rates

Described by Strauch and Murray in 1967, the rodent epigastric free flap remains a versatile tool for microsurgery research and training. We report herein three sequential phases of our quest to improve efficiency and effectiveness of the original technique, making it more accessible to more microsurgeons. Ninety-six allotransplants were performed. Surgical technique, complication rates, clinical findings, and histopathologic correlation of each phase are reported. In phase I, two experienced microsurgeons employed the original technique and succeeded in 77% of the procedures. In phase II, two junior microsurgeons achieved a patency rate of 16.6% using the same technique, as opposed to 100% in phase III, utilizing the not-yet-described simplified flow-thru technique. Although patency rate using the original method varies from 9 to 78% (according to other reports), this technical modification can increase even the less experienced microsurgeons' success rates, perpetuating the use of Strauch's epigastric flap in experimental microsurgery.     

The Role of Intra-Arterial Calcium Stimulation Test with Hepatic Venous Sampling (IACS) in the Management of Occult Insulinomas

Background Occult insulinomas remain a clinical challenge. Specifically designed protocols are necessary to aid detection and facilitate a focused pancreatic exploration. Methods Seventeen non-multiple endocrine neoplasia (non-MEN) patients referred to this medical center in the past 10 years because of equivocal diagnosis, failure of previous operation or difficulty in localization for insulinomas were studied. A routine intra-arterial calcium stimulation test with venous sampling (IACS test) was done for lesion localization. An exploratory laparotomy with intraoperative ultrasound (IOUS) examinations was performed. Results Preoperative imaging (sonography, high-resolution computed tomography scan, and magnetic resonance imaging) found six insulinomas, and IOUS found an additional six in the pancreatic regions; all were compatibly indicated by the IACS test. The remaining five patients with occult lesions by IOUS were treated by 40% (1) or 60–70% (4) distal pancreatectomies when insulin gradients were demonstrated on calcium stimulation to the splenic or to the superior mesenteric artery, respectively, and nesidioblastosis was found in each pathology examination. There were no complications related to the arterial stimulation and venous sampling (ASVS) test. No patient had recurrent hyperinsulinism, permanent morbidity, or mortality from surgery. Conclusions IACS test helps in the diagnosis of equivocal pancreatogenous hypoglycemia, indicating the pancreatic region of priority exploration and guiding a pancreatic resection.     

Surgical site infections and supplemental perioperative oxygen in colorectal surgery patients: a systematic review

BACKGROUND: Four randomized trials have evaluated the impact of supplemental perioperative oxygen on the incidence of surgical site infections (SSIs), with mixed results. The objectives of this meta-analysis were: (1) To evaluate further the effect of supplemental perioperative oxygen on SSIs after colorectal surgery; and (2) to generate a strategy for future studies to determine definitively the value of this intervention. METHODS: We conducted a MEDLINE search to identify randomized trials of supplemental perioperative oxygen with a primary endpoint of SSI. Fixed-effects and random-effects models were employed, and the null association was tested for each. Tests also were performed for heterogeneity and publication bias. RESULTS: Four studies were identified that satisfied the search criteria. The total number of patients was 943, of whom 477 received supplemental oxygen and 466 served as controls. The pooled risk ratio (RR) for SSI favored the patients who received supplemental oxygen (RR = 0.68; 95% confidence interval [CI] 0.49, 0.94), but this difference was not maintained with a random-effects model (RR = 0.73; 95% CI 0.42, 1.28; p = 0.27). Heterogeneity was present among the studies. There was no evidence of publication bias. CONCLUSIONS: Supplemental perioperative oxygen is associated with a lower risk of SSI in patients undergoing colorectal surgery. The heterogeneity among the individual reports may be secondary to differences in study protocols.