Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

The protective effect of alpha-lipoic acid in experimental ovarian ischaemia-reperfusion injury

BACKGROUND: We investigated the effect of alpha-lipoic acid (LA) on reperfusion injury in a rat ovarian torsion-detorsion model. The changes in tissue and plasma levels of malondialdehyde (MDA), end-product of lipid peroxidation, superoxide dismutase (SOD), xanthine oxidase (XO) and nitric oxide (NO), were determined. Ovarian histopathological findings were scored and compared among groups. MATERIALS AND METHODS: Thirty-two female Sprague-Dawley rats were divided into four groups. Sham operation was performed in group I; in group II only ovarian torsion was performed. Group III received intraperitoneal injections of saline, and group IV received LA via intraperitoneal injections (LA group: aqueous solution at 36 mg/kg of body weight per day, saline group: equal volume of saline) 21, nine, and one hour before torsion of the ovary. Rats in the torsion group were killed after 360 degrees clockwise adnexial torsion for three hours, and ovaries were harvested. After three hours of adnexial detorsion, the rats in saline group and LA group were killed and adnexa were surgically removed. RESULTS: Ovarian tissue damage scores were significantly different among groups and were seen to correlate with tissue MDA levels. Ovarian tissue and serum MDA, NO and serum XO levels in the group III were significantly higher than those of the groups I and IV (P<0.05). The serum levels of SOD in the group III were significantly lower than those of the groups I and IV (P<0.05). CONCLUSION: These results suggest that LA pretreatment has beneficial effects in the prevention of ischaemia-reperfusion injury of the ovaries.     

Resveratrol Triggers Apoptosis Through Regulating Ceramide Metabolizing Genes in Human K562 Chronic Myeloid Leukemia Cells

Cancer is a major worldwide health problem and one of the leading causes of death either in developed or developing countries. Plant extracts and derivatives have always been used for various disease treatments and many anticancer agents issued from plants and vegetables are clinically recognized and used all over the world. Lycium europaeum (Solanaceae) also called “wolfberry” was known since ancient times in the Mediterranean area as a medicinal plant and used in several traditional remedies. The Lycium species capacity of reducing the incidence of cancer and also of halting or reserving the growth of cancer was reported by traditional healers. In this study, the antiproliferative capacity, protective properties, and antioxidant activity of the hydro-alcoholic fruit extract of Lycium europaeum were investigated. Results showed that Lycium extract exhibits the ability to reduce cancer cell viability, inhibits proliferation, and induces apoptosis in A549 human lung cancer cells and PC12 rat adrenal medulla cancer cells, in a concentration- and time-dependent manner. Cytotoxic effect on normal rat cerebellum granule cells was assessed to be nonsignificant. Results also showed that Lycium fruit extract protected lipids, proteins, and DNA against oxidative stress damages induced by H₂O₂ via scavenging reactive oxygen species.     

Incidence and Impact of Documented Eradication of Breast Cancer Axillary Lymph Node Metastases Before Surgery in Patients Treated With Neoadjuvant Chemotherapy

OBJECTIVE: To determine the incidence and prognostic significance of documented eradication of breast cancer axillary lymph node (ALN) metastases after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is being evaluated in patients with earlier-stage operable disease. METHODS: One hundred ninety-one patients with locally advanced breast cancer and cytologically documented ALN metastases were treated in two prospective trials of doxorubicin-based neoadjuvant chemotherapy. Patients had breast surgery with level I and II axillary dissection followed by additional chemotherapy and radiation treatment. Nodal sections from 43 patients who were originally identified as having negative ALNs at surgery were reevaluated and histologically confirmed to be without metastases. An additional 1112 sections from these lymph node blocks were obtained; half were stained with an anticytokeratin antibody cocktail and analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 191 patients with positive ALNs at diagnosis, 23% (43 patients) were converted to a negative axillary nodal status on histologic examination (median number of nodes removed = 16). Of the 43 patients with complete axillary conversion, 26% (n = 11) had N1 disease and 74% (n = 32) had N2 disease. On univariate analysis, patients with complete versus incomplete histologic axillary conversion were more likely to have initial estrogen-receptor-negative tumors, smaller primary tumors, and a complete pathologic response in the primary tumor. The 5-year disease-free survival rates were 87% in patients with preoperative eradication of axillary metastases and 51% for patients with residual nodal disease after neoadjuvant chemotherapy. Of the 39 patients with complete histologic conversion for whom nodal blocks were available, occult nodal metastases were found in additional nodal sections in 4 patients (10%). At a median follow-up of 61 months, the 5-year disease-free survival rates were 87% in patients without occult nodal metastases and 75% in patients with occult nodal metastases. CONCLUSIONS: Neoadjuvant chemotherapy can completely clear the axilla of microscopic disease before surgery, and occult metastases are found in only 10% of patients with a histologically negative axilla. The results of this study have implications for the potential use of sentinel lymph node biopsy as an alternative to axillary dissection in patients treated with neoadjuvant chemotherapy.     

Nonoliguric renal failure after transurethral resection of prostate

PURPOSE: To define the relation of nonoliguric renal failure to transurethral resection of the prostate (TURP), its clinical importance, and predictive factors. PATIENTS AND METHODS: The files of 439 patients who had undergone TURP at Hacettepe University School of Medicine, Department of Urology, between January 1991 and 1994 were analyzed. The patients were divided into three groups according to postoperative serum creatinine concentration and the presence of clinical signs and symptoms of TUR syndrome (Group I: patients with preoperative and postoperative creatinine in the normal range; Group II: patients suffering nonoliguric renal failure; and Group III: patients with TUR syndrome). The data of the groups were compared in terms of factors influencing nonoliguric renal failure. RESULTS: The mean postoperative concentrations of sodium, blood urea nitrogen, creatinine, and albumin in Groups II and III were statistically different from those in Group I (P < 0.001). There was a moderate relation between hyponatremia and the occurrence of nonoliguric renal failure (r(s) = -0.56). Capsule perforation increased the risk of nonoliguric renal failure 10.6 fold. All of the patients were managed by a conservative approach, and none of the patients died or progressed to end-stage renal disease. They were all discharged with a mean hospitalization period of 7 days and normal renal function tests. CONCLUSION: Nonoliguric renal failure was thought to be an early step in the pathophysiology of TUR syndrome with acute renal failure. It is an asymptomatic clinical picture that is undiagnosed unless laboratory examinations are performed. A conservative therapeutic approach is enough.     

Epidural neostigmine produces analgesia but also sedation in women after cesarean delivery

BACKGROUND: Intrathecal neostigmine produces analgesia but also nausea, limiting its utility. In contrast, epidural administration of neostigmine has been suggested to produce postoperative analgesia without nausea in nonpregnant patients. The purpose of this study was to examine the dose range for efficacy and side effects of epidural neostigmine in women at cesarean delivery receiving combined spinal-epidural anesthesia. METHODS: After institutional approval and informed consent, 80 patients for elective cesarean delivery were given combined spinal-epidural anesthesia with 8 mg hyperbaric bupivacaine plus 10 microg fentanyl. Patients were randomized to receive either saline or 75, 150, or 300 microg neostigmine (n = 20 per group) in 10 ml saline after cord clamping. Pain, morphine consumption, and side effects were monitored for 24 h. RESULTS: Global pain assessment for the first 24 h was reduced from 5.4 +/- 0.2 in the saline group to 3.0-3.5 +/- 0.3 in the neostigmine groups, dose independently. Correspondingly, global satisfaction with neostigmine was also improved (P < 0.05). Nausea and morphine consumption were similar among groups. Intraoperative shivering and sedation were increased in the 300-microg neostigmine group only (P < 0.05), and postoperative sedation was increased by neostigmine in a dose-independent fashion (P < 0.05). CONCLUSIONS: Epidural neostigmine produced modest analgesia in women after cesarean delivery. In contrast with previous reports, which focused primarily on nausea, these data suggest that epidural neostigmine can also produce mild sedation for several hours. These data suggest a limited role for single bolus-administration epidural neostigmine for analgesia after cesarean delivery. They also support future study of epidural neostigmine for obstetric analgesia.     

Upper cervical vertebrae movement during intubating laryngeal mask, fibreoptic and direct laryngoscopy: a video-fluoroscopic study

BACKGROUND AND OBJECTIVE: Minimizing cervical vertebrae motion during endotracheal intubation is important in patients with cervical instability. The aim of this study was to compare upper cervical spine extension during endotracheal intubation using three different techniques. METHODS: Duration of intubation and movement of upper cervical vertebrae during endotracheal intubation were compared in 33 patients undergoing lumbar laminectomy. Patients requiring tracheal intubation under general anaesthesia and neuromuscular blockade were randomly allocated into three groups - direct laryngoscopy, intubating laryngeal mask (LM) airway and fibreoptic laryngoscopy. The procedure was recorded by video-fluoroscopy and analysed with computer-assisted measurements. The maximum movement of the C1/C2 and C2/C3 vertebrae during intubation were obtained. Data were analysed using one-way analysis of variance with Bonferroni and Kruskal-Wallis tests. RESULTS: We found statistically significant movement between the first and second, but not between the second and third cervical vertebrae. The mean (+/-SD) movement at C1/C2 was 10.2 +/- 7.3 degrees with direct laryngoscopy, 5.0 +/- 6.3 degrees with LM and 1.6 +/- 3.2 degrees with fibreoptic laryngoscopy. This difference was statistically significant (P = 0.01) between the direct and fibreoptic laryngoscopy groups. The maximum movement at C2/C3 was 2.2 +/- 10.1 degrees with direct laryngoscopy, 3.5 +/- 5.1 degrees with LM and 0.5 +/- 3.2 degrees with fibreoptic laryngoscopy. Duration of intubation was significantly longer in the intubating LM group (P < 0.001). CONCLUSION: We conclude that fibreoptic laryngoscopy is the more suitable intubation technique when cervical spine movement is not desired.