Erythropoietin against cisplatin-induced peripheral neurotoxicity in rats

Cisplatin (CDDP) is a potent anticancer drug, and neurotoxicity is one of its most important dose-limiting toxicities. In this study we investigated the role of recombinant human erythropoietin (rhuEPO) for protection against CDDP-induced neurotoxicity. All experiments were conducted on female Wistar-albino rats. Animals were randomly assigned to three groups. Group A received only CDDP, group B received CDDP plus rhuEPO, and group C received only rhuEPO. Electroneurography (ENG) was done in the beginning and at the end of 7 wk, then the rats were sacrificed and the sciatic nerve was removed for histopathological examination. The mean initial latency was 2.7438 ms in group A, 2.4875 ms in group B, and 2.62 ms in group C. After 7 wk of treatment, the latency was 2.4938, 2.6313, and 2.3900 ms, respectively. The difference in latencies was not statistically significant. The amplitude of compound muscle action potential (CMAP) was 12.8125 mV, 14.3875 mV, and 14.5600 mV before the treatment and 8.4875, 12.8250, and, 13.0800 mV after treatment, respectively. Amplitude of CMAP was significantly greater in rhuEPO-treated groups (groups B and C) compared to cisplatin only Group A. The mean area of CMAP was 12.2625, 12.3500, and, 12.2800 mV s before the treatment and 5.7125, 10.6463, and 9.1600 mV s after the treatment, respectively. The area of CMAP was significantly larger in rhuEPO-treated groups. In histopathological studies thick, thin, and total number of nerve fibers were 4053, 5050, and 9103, in group A, 5100, 8231, and 13331, in group B, and 5264, 6010, and 11274, in group C respectively. In the microscopic examination active myelinization process was observed in rhuEPO-treated groups. We concluded that at the given dose and schedule CDDP-induced motor neuropathy and rhuEPO prevented this neuropathy by sparing the number of normal nerve fibers and by protecting the amplitude and area of CMAP. We concluded that rhuEPO may also play a role in active myelinization and it is an active agent in protection against CDDP-induced peripheral neuropathy, warranting further clinical studies.     

Mixed urinary incontinence symptoms: urodynamic findings,incontinence severity,and treatment response

OBJECTIVE: To investigate the relationship between the symptom of mixed urinary incontinence and incontinence severity, urodynamic findings, and treatment response. METHODS: This is a secondary analysis of data from 553 women randomized into a double-blind, placebo-controlled study evaluating duloxetine (serotonin-norepinephrine reuptake inhibitor) for the treatment of predominant stress urinary incontinence. Assessment variables included incontinent episode frequency, the Incontinence Quality of Life Questionnaire (I-QOL), and the Patient Global Impression of Severity Scale (PGI-S). Urge symptoms were identified with three urge I-QOL questions not included in corrected I-QOL calculations. RESULTS: At baseline, 171 women (31%) had mixed urinary incontinence. They had more severe baseline urinary incontinence than did those with stress urinary incontinence (mean incontinent episode frequency 14.3 versus 10.5; PGI-S normal or mild 26.5% versus 70.4%; mean corrected I-QOL 59.1 versus 79.9; all Ps <.001). Baseline urodynamics were performed on a subset of 86 women. Subjects with both urodynamic stress incontinence and detrusor overactivity had less severe incontinence compared with subjects with only urodynamic stress incontinence. Both mixed urinary incontinence and stress urinary incontinence groups had significant decreases in median incontinent episode frequency at a 40 mg per day (62% and 58%, respectively) and 80 mg per day (63% and 65%) duloxetine dose compared with placebo (33% and 44%; all Ps <.05). Response was not dependent on the type of symptoms (interaction P =.47). CONCLUSION: For women presenting with predominant stress urinary incontinence symptoms, the major determinant of concurrent urge symptoms was incontinence severity and not the pathophysiologic condition(s) causing the incontinence; duloxetine demonstrated equal efficacy for women with mixed urinary incontinence and pure stress urinary incontinence.     

Vaginal intraepithelial neoplasia: treatment by carbon dioxide laser and risk factors for failure

OBJECTIVE: To evaluate the effectiveness of CO(2) laser ablation of vaginal intraepithelial neoplasia (VAIN) and to define prognostic factors. STUDY DESIGN: Medical records of 24 patients with VAIN II or III, treated by CO(2) laser ablation from 1990 to 1998 were reviewed. The grade, location, and focality of the lesions, the age, follow-up period and menopausal status of the patients, the power and duration of laser ablation, the presence of concurrent cervical or vulvar neoplasia or previous hysterectomy were evaluated as possible prognostic factors. RESULTS: Ablations of the VAIN were successfully accomplished in all of the patients with a mean period of 25.2+10.2 min, including additional simultaneous ablations of the cervix or vulva in eight (33.3%) patients. There was no early or late major complication. VAIN was completely eliminated in 17 (70.8%) patients after the first and in 19 (79.2%) patients after multiple episodes of ablation with a mean follow-up of 26.7+19.6 months. VAIN progressed to invasive vaginal carcinoma in one woman. None of the evaluated prognostic factors was found to be related to the persistence or recurrence. CONCLUSION: CO(2) laser ablation was a safe and effective method for the treatment of VAIN. However, since no prognostic factor was defined, all patients should be closely evaluated for persistence, recurrence or progression to invasion.     

p53 overexpression as a prognostic indicator in endometrial carcinoma

PURPOSE: To investigate the prognostic value of p53 overexpression in endometrial adenocarcinoma cases of different stages and histologic subtypes. METHODS: One hundred and eleven surgically staged endometrial carcinoma (EC) cases from 1996 to 2000 constituted this retrospective study group. Prognostic factors determined through the evaluation of surgery specimens by co-author pathologist, were surgical stage, tumor size, histology, histologic and nuclear grade, myometrial invasion, adnexal/serosal metastasis, peritoneal cytology, retroperitoneal lymph node involvement p53 overexpression was assessed via immunohistochemical staining. Tissues that expressed p53 were considered as positive p53 staining. In terms of degree of staining, 1-29%, 30-90% and 80-100% of tumoral tissue stained with p53 were considered to be mild, moderate and high p53 staining, respectively. RESULTS: Mean age and follow-up period of the study group were 58.2 +/- 10.6 years and 33.4 +/- 2.7 months, respectively. Percentages of cases surgically staged as early (I-II) and advanced (III-IV) FIGO stages were 65.8% (n: 73) and 34.2% (n: 38), respectively. Cases with positive p53 staining had a significantly high mean survival period compared with those with negative p53 staining (86.6 +/- 6.0 vs 49.1 +/- 8.1, p < 0.001). p53 overexpression was statistically detected to be high in Stage III-IV tumors, non-endometrioid histologic subtypes (p = 0.019), histologic and nuclear grade 2-3 tumors (p < 0.001), adnexal/serosal metastasis (p = 0.001), lymph node involvement (p = 0.012), and positive peritoneal cytology (p = 0.017). The degree of p53 staining was remarkably correlated with survival. In cases with mild and high p53 staining, mean survival times were 47.1 +/- 7.0 months and 57.0 +/- 13.1 months, respectively (p = 0.0003) compared to those with high p53 staining. On univariate analysis, all of the prognosticators, including p53 staining (p < 0.001) and degree of p53 staining (p < 0.001) appeared to be independent risk factors for poor prognosis. On multivariate analysis, only pelvic lymph node involvement (p = 0.03), serosal/adnexal involvement (p = 0.004), and positive peritoneal cytology (p = 0.01) were found to be independent prognosticators of survival while p53 expression (p = 0.743) and degree of p53 staining (p = 0.802) were not detected as independent prognosticators. CONCLUSION: p53 overexpression is strongly related to poor prognostic indicators in endometrial adenocarcinoma. Although in this study p53 overexpression was not detected as an independent prognosticator, additional studies with large data set are needed to evaluate the prognostic value of p53 expression.     

Bcl-2 expression in preinvasive and invasive cervical lesions

PURPOSE: To determine the correlation between bcl-2 expression and clinicopathological findings in cervical intraepithelial neoplasias (CIN I, II, III) and invasive cervical lesions, and its effect on overall survival rate. METHODS: Fifty specimens derived from 22 preinvasive and invasive cervical cancer cases up to surgical stage IIb (21 squamous cervical carcinoma and 7 adenocarcinoma cases) were preserved in paraffin blocks from primary surgery and constituted the study group. Tissues were processed and stained by immunohistochemical methods to assess the degree of bcl-2 expression. RESULTS: Positive bcl-2 expression was detected in 54% (13/21) of invasive lesions, while negative in 46% of cases. In CIN's, overall bcl-2 positivity was detected in 68% of cases. Bcl-2 expression was highly relevant between low grade (CIN I) and high grade (CIN II-III) lesions (p < 0.05). As regards degree of tissue staining for bcl-2 in CIN III cases, a statistically relevant difference was detected in comparison with low-grade preinvasive lesions (p < 0.05). In invasive cervical cancer cases, patients with bcl-2 positivity had a longer survival rate. By using the Cox regression model, univariate analysis did not show any specific prognostic factor to be important for survival rate, whereas, on multivariate analysis, histopathologic subtypes (p = 0.0390) and stage of tumor (p = 0.0451) had a statistically significant impact on overall survival rate. CONCLUSIONS: Bcl-2 expression, especially in preinvasive lesions, may play a role in the apoptotic process and be regarded as a marker for disease progression. In invasive cervical carcinomas, bcl-2 expression has not been shown to be effective in overall survival rates.     

Outcome of nephron-sparing surgery: elective versus imperative indications

INTRODUCTION: The increase in the detection of renal tumors incidentally in earlier stages has enhanced the enthusiasm for nephron-sparing surgery (NSS). PATIENTS AND METHODS: We performed NSS in 76 patients (53 male, 23 female) with a mean age 52.3 between December 1988 and September 2001. Patients were sub-classified into 2 groups as elective or imperative indication group. They were compared regarding surgical technique, time of surgery, pathological analysis, complications, and disease free status. RESULTS: Elective indication group (group I) with a normal contralateral kidney consisted of 50 patients, whereas there were 26 patients in the imperative indication group (group II). Tumors were incidentally detected in 63%; 74% in group I and 42% in group II. Although the mean diameter of the tumor was slightly higher in group II (39.1 vs. 36.3 mm), this difference did not reach statistical significance (p > 0.05). The partial nephrectomy was performed more frequently compared to enucleation in group I (90 vs. 69%, p = 0.050). However, the mean operation time as well as the mean clamping time did not differ significantly between the two groups (p > 0.05). In the histological evaluation tumors were benign in 16 (21%) and malignant in 60 patients. All of the patients but one with renal cell carcinoma had stage T1-T2 disease. Major complications were observed in 14 (18%) and 12 were from group II. Complication rate was significantly higher in group II (p = 0.000). Of 60 patients with renal cell carcinoma, 2 died of unrelated causes. One patient died with multiple visceral metastases. One patient was lost to follow-up. In the remaining 56 patients with a mean follow-up of 37.1 months (1-152), local recurrence or distant metastases were not detected. Serum creatinine levels have remained almost the same compared to preoperative levels (1.2 +/- 0.6 vs. 1.5 +/- 0.9). Overall and cancer-specific survivals were 100 and 100% in group I, 85 and 95% in group II, and 94 and 98% for the entire patient population, respectively. CONCLUSION: NSS is an effective and reliable treatment in low stage renal tumors. It prevents unnecessary nephrectomy in benign lesions that could not be diagnosed preoperatively. However, the patients who underwent NSS with elective indication outcome with better results, compared to those with imperative indication.     

Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer

OBJECTIVE: In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. METHODS: A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. RESULTS: An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. CONCLUSIONS: We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.