CI-980 for the Treatment of Recurrent or Progressive Malignant Gliomas: National Central Nervous System Consortium Phase I-II Evaluation of CI-980

Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma.

Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses.

Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m², given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m² per cycle. Treatment response was based on serial MRI imaging characteristics.

Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI=0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen.

Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.     

Revisiting induction chemotherapy for head and neck cancer. References and reviews

Squamous cell carcinomas of the head and neck are highly responsive to induction chemotherapy. However, randomized trials have failed to demonstrate a survival advantage with the addition of induction chemotherapy to locoregional therapy consisting of surgery and/or radiation therapy. Currently, concomitant radiation and chemotherapy has emerged as a standard and has optimized locoregional control in head and neck cancer. In this setting, the addition of induction chemotherapy may further improve outcome by enhancing both locoregional and distant control. As interest in induction regimens is renewed, we elected to conduct a systematic review of trials of induction chemotherapy for locoregionally advanced head and neck cancer. The most studied combination-cisplatin plus fluorouracil (5-FU)--achieves objective response rates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregional therapy alone. The introduction of a taxane into induction chemotherapy regimens has produced promising results. Induction chemotherapy should be the subject of further clinical research in head and neck cancer. Randomized clinical trials in which the control arm is concurrent chemoradiotherapy and the experimental arm is induction chemotherapy followed by concurrent chemoradiotherapy are planned. Platinum/taxane combinations are the preferred regimens for further study in the induction setting and a suitable platform with which to investigate the addition of novel targeted agents.     

Prevention of retrograde calculus migration with the Stone Cone

Retrograde calculus migration during ureteroscopic lithotripsy remains a problem in 5–40% of cases. We assessed the safety and efficacy of the Stone Cone device, in comparison with the standard flat wire basket. A total of 56 consecutive patients with ureteral calculi, suitable for ureteroscopic extraction and/or lithotripsy, where included in this prospective study. Patients were randomly allocated into two groups. In group A (30 patients), we used the Stone Cone, while in group B (26 patients) we used the standard flat wire basket. The Stone Cone was placed through a cystoscope under fluoroscopic guidance, or when necessary under direct ureteroscopic control. Whenever necessary, intracorporeal electrohydraulic lithotripsy took place in both groups. Statistical significance was assessed by the paired t-test. The mean operative time was 48.5 min in group A, and 42.4 min in group B. Intact calculus extraction was possible in 16.6% in group A, and in 7.6% in group B (P<0.01). Retrograde stone migration was revealed in 23% in group B only (P<0.001). Also, residual fragments >3 mm were recorded in 30.7% in group B only (P<0.001). None of the patients in group A required auxiliary procedures, in contrary to 23% in group B (P<0.001). No major complications were recorded in group A, while in group B a case of major ureteral mucosal abrasion was recorded. The Stone Cone is safe and efficient in preventing retrograde stone migration and in minimizing residual fragments during ureteroscopic lithotripsy in comparison with the flat wire basket.     

DOES THE MANAGEMENT OF BLADDER PERFORATION DURING TRANSURETHRAL RESECTION OF SUPERFICIAL BLADDER TUMORS PREDISPOSE TO EXTRAVESICAL TUMOR RECURRENCE?

PURPOSE: We evaluated the impact of a bladder perforation during transurethral resection of superficial bladder tumor on extravesical tumor recurrence and patient prognosis. We also defined potential risk factors for extravesical recurrence prospectively giving emphasis to the management of the perforation. MATERIALS AND METHODS: The medical records of 3,410 patients were reviewed. Parameters recorded included patient age and sex, tumor stage, grade, number, size and location at the time of perforation, the type of bladder perforation (extraperitoneal vs intraperitoneal) and the way the perforation was managed (open surgical repair vs conservative treatment). Logistic regression analysis was used to identify risk factors for extravesical recurrence. Cox regression analysis was used to compare cancer specific survival. RESULTS: A total of 34 cases of bladder perforation were recorded, 4 patients were treated with open surgery and 30 treated conservatively. The 4 patients who underwent open surgery presented with extravesical recurrence after a mean followup of 7.5 months. The remaining 30 patients had no evidence of extravesical recurrence after a mean followup of 60 months (p <0.001). Of the patients with extravesical relapse 3 died of disease. The surgical management of bladder perforation was the best predictor of extravesical recurrence (p <0.001, r = 1.13), followed by an intraperitoneal localization of the perforation (p =0.0003, r = 0.67) and tumor size (p =0.01, r = 0.42). CONCLUSIONS: Surgical repair of a bladder perforation during transurethral resection of bladder tumor increases the risk of extravesical tumor cell recurrence and negatively affects patient prognosis.     

Bile Duct Injuries Associated with Laparoscopic and Open Cholecystectomy: An 11-Year Experience in One Institute

Purpose Bile duct injury (BDI) represents the most serious complication of laparoscopic cholecystectomy (LC). The aim of this retrospective single-institution study was to evaluate the real incidence of BDI during laparoscopic and open cholecystectomy (OC) in a tertiary academic center in Athens, Greece.Methods Between January 1991 and December 2001, 3 637 patients underwent cholecystectomy in our department; as LC in 2 079 patients (LC group) and as OC in 1 558 patients (OC group). All the LCs were performed or supervised by five staff surgeons and all the OCs were performed or supervised by another five staff surgeons.Results There were 13 BDIs associated with LC (0.62%) and 6 associated with OC (0.38%) (P = 0.317). There was one death associated with BDI after LC. Only two (15.4%) of the BDIs associated with LC occurred within the proposed learning curve limit of 50 LCs per individual surgeon.Conclusion Laparoscopic cholecystectomy is safe and is not associated with a higher incidence of BDI than OC. Moreover, we did not find that the learning curve for LC affected BDI occurrence.     

Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease

Summary Endothelial dysfunction is considered to be the first step in atherogenesis as well as a predictor of adverse cardiovascular events in patients with coronary artery disease (CAD), while endothelial function improvement is associated with improved clinical outcome. Nebivolol is a beta₁-adrenoreceptor antagonist with an independent beneficial action on endothelial function, increasing nitric oxide bioavailability. The aim of the present study was to examine the effects of nebivolol on endothelial function in the brachial artery in patients with CAD compared with another selective beta₁ adrenergic receptor antagonist, atenolol. Thirty-five patients with stable CAD were randomized to receive either 5 mg nebivolol (n = 17) or 50 mg atenolol (n = 18) daily for 4 weeks. Each patient underwent measurement of endothelial function by means of flow-mediated dilatation (FMD) of the brachial artery before and after 4 weeks of treatment. All vasoactive drugs and cardiovascular risk factors were comparable in the two groups. No significant differences were observed between the two groups at baseline in FMD. In the atenolol group FMD remained unchanged at the end of the 4-week treatment, but in patients treated with nebivolol FMD showed a significant increase by the end of the treatment period (3.9 ± 2.7% vs. 5.6 ± 2.9%, p = 0.047) leading to a significantly higher value compared to patients treated with atenolol (5.6 ± 2.9% vs. 3.4 ± 3.2%, p = 0.041). Beta₁ blockade by nebivolol but not atenolol improves endothelial dysfunction in patients with CAD, an effect that might further reduce the risk for cardiovascular events in patients with CAD.     

Unusual retrograde movement of a safety-pin ingested by an infant

Here we present the first reported case of an ingested open safety-pin in a 7-mo-old boy that migrated from the stomach to the oesophagus. CONCLUSION: This rare complication is probably due to a gastro-oesophageal reflux effect, and for this reason we propose that all infants with safety-pins and other sharp objects in the stomach should be positioned in a semi-upright position.     

Treatment of cutaneous leishmaniasis with cryosurgery

BACKGROUND: The management of cutaneous leishmaniasis with topical methods, if effective, can spare patients from long and costly inpatient treatments. METHODS: Seventeen patients with cutaneous leishmaniasis were treated with cryosurgery using liquid nitrogen as the cryogen. Two cycles of 10-30 s freezing time were used and repeated at 3-week intervals. RESULTS: All patients responded well to therapy with excellent cosmetic results and no relapse in any case. Side-effects were rare. CONCLUSIONS: Cutaneous leishmaniasis can be successfully treated with a simple protocol of cryosurgery with minor side-effects.