Changes of topoisomerase IIalpha expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival.

PURPOSE: To assess the value of changes in the expression of topoisomerase IIalpha (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy. PATIENTS AND METHODS: Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: Neoadjuvant chemotherapy resulted in a significant reduction in the percentage of cells expressing TopoII (P < 0.0001). No significant change was observed for HER-2. TopoII and HER-2 expression before chemotherapy predicted tumor response to treatment. Changes in TopoII expression after chemotherapy were strongly associated with a poor relapse-free survival (P < 0.0001) in a Cox multivariate analysis adjusted for other clinicopathologic prognostic factors. CONCLUSION: Changes in TopoII expression after anthracycline-based neoadjuvant chemotherapy is an independent predictor of a poor relapse-free survival in patients with breast cancer. Tumor cells displaying an increased TopoII expression after treatment may be responsible for relapses, and may, therefore, define a group of patients with anthracycline-resistant breast cancer.     

Sentinel Node Biopsy Interpretation: The Milan Experience

From March 1996 to December 1999 we performed 1,266 sentinel node biopsies (SNBs) in patients with small breast cancers. The technique is to inject technetium 99m-labeled albumin particles close to the tumor, locate the sentinel node (SN) scintigraphically, and use a handheld gamma-detecting probe to guide its removal via a small incision during breast surgery. Our experience was divided into three phases. In the first phase, complete axillary dissection was performed to assess the accuracy of SNB in predicting axillary status. We also assessed safety, perfected tracer injection technique, determined optimal particle size and radioactivity levels, optimized lymphoscintigraphic scanning, and perfected the surgical technique. The SN was identified and removed in 98.7% of cases. Comparison with complete axillary dissection showed that the SN predicted axillary status in 96.8% of cases. However, use of an intraoperative frozen section method predicted axillary status in only 86.5% of cases. In the second phase we developed a new method for intraoperative histologic analysis. Extensive sampling (up to 60 sections/SN) and an experienced pathologist proved more important than use of antikeratin immunostaining in identifying tumor cells, and the new method has the accuracy of a definitive histologic examination. The third phase, a randomized trial, closed at the end of 1999. Trial objectives were to confirm that the SN predicts axillary status, to determine the number of axillary relapses, and to assess overall and disease-free survival. Patients were randomized in the operating room to complete axillary dissection or SNB. If the SN was positive, complete axillary dissection was performed; if the SN was negative, no further axillary treatment was given. We expect the trial to confirm our clinical experience that SNB is a safe and accurate procedure for staging patients with early breast cancer and a clinically negative axilla.     

Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study.

PURPOSE: To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (> or = 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS: We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satariano's index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS: These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL-independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two-fold higher probability of having an elevated Satariano's index than independent patients. A strong association emerged between PS and CGA, with a nearly five-fold increased probability of having a poor PS (ie, > or = 2) recorded in patients dependent for ADL or IADL. CONCLUSION: The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients.     

Overexpression of vascular endothelial growth factor-A165 enhances tumor angiogenesis but not metastasis during beta-cell carcinogenesis.

The pivotal role of vascular endothelial growth factor (VEGF-A) in the regulation of angiogenesis, in particular in the onset and maintenance of tumor angiogenesis, has been demonstrated repeatedly in experimental model systems and, more recently, in clinical trials. Experimental evidence has also suggested that up-regulated expression of VEGF-A may cooperate with other genetic or epigenetic changes to induce or accelerate tumor progression to invasive and metastatic cancers. Here we report the generation of transgenic mouse lines that express human VEGF-A165 under the control of the rat insulin promoter in the beta cells of pancreatic islets of Langerhans (Rip1VEGF-A). These mice do not exhibit detectable changes in islet development, vascularization, or physiology. Intercrosses of these mice with a transgenic mouse model of pancreatic beta cell carcinogenesis (Rip1Tag2) result in an earlier onset of tumor angiogenesis and with it accelerated tumor growth and mortality. The transition from benign tumors (adenoma) to malignant tumors (carcinoma) is modestly accelerated; however, tumor metastases are not observed. Our findings indicate that in beta-cell tumorigenesis, overexpression of VEGF-A165 accelerates the onset of tumor angiogenesis and with it tumor progression but is not sufficient to induce tumor metastasis.     

Chronic liver herniation through a right Bochdalek hernia with acute onset in adulthood

Congenital right diaphragmatic hernia of Bochdalek rarely occurs in adults and usually is asymptomatic. We report a right Bochdalek hernia with chronic liver herniation and intestinal malrotation in a 55-year old woman who presented with acute intestinal occlusion. The diagnosis required definitive confirmation by CT scan. With impending strangulation, emergency surgery through a thoracoabdominal approach resulted in an easy hernia repair and reduced the technical difficulties due to the intestinal malrotation.     

Dopamine and morphine stimulate nitric oxide release in human endometrial glandular epithelial cells

OBJECTIVE: Previous studies have shown that human endometrial glandular epithelial cells contain endothelial nitric oxide synthase indicating that the endometrium might produce nitric oxide (NO). We conducted this study to identify stimuli that can activate a transient NO release from endometrial glandular epithelial cells because NO is an important intracellular and intercellular signal transduction pathway in reproductive cycle. METHODS: Endometrial glandular epithelial cells, free of endothelial cells, were isolated from human endometrial specimens and maintained viable in RPMI 1640 medium with 2% fetal bovine serum for 2-4 days. Nitric oxide release from the glandular cells in response to stimuli was monitored continuously amperometrically. RESULTS: Among the substances examined, we found that dopamine and morphine stimulated a transient surge of NO production that was dose-dependent, whereas estrogen, progesterone, or relaxin (RLX) had no short-term effect on NO release. Cells treated with RLX or dopamine for 4 days enhanced the dopamine-induced NO release fourfold to sixfold, with the peak of the NO surge shifting from 35 to 15 seconds. CONCLUSION: Endometrial glandular cells were capable of producing NO. Dopamine and morphine were potent stimuli for a transient surge of NO release from endometrial glandular cells. Furthermore, prolonged exposure to dopamine or RLX enhanced the sensitivity of NO release in endometrial glands.     

Recurrent antiphospholipid-related deep vein thrombosis as presenting manifestation of systemic lupus erythematosus

Antiphospholipid antibodies (aPL) are frequently associated with thrombotic disorders in the so-called antiphospholipid syndrome. Together with anticardiolipin antibodies (aCL), lupus anticoagulant (LA) is the main diagnostic tool for aPL detection. Since LA determination is based on the finding of prolonged clotting time in vitro, concomitant anticoagulant therapy may significantly interfere with its detection. We report a case of a boy in whom recurrent aPL-related thrombosis heralded for several months the onset of systemic lupus erythematosus (SLE). Abnormally increased in vitro clotting times at the time of the second thrombotic event led to the suspicion of the presence of LA activity. However, this latter finding was difficult to interpret since the patient was already on heparin treatment at the time of our first observation. Thus, LA was assayed using a commercial kit in which a heparin neutralizer is included (Staclot LA). Two consecutive samples from the patient were compared with eight patients on anticoagulant therapy for non-aPL-related thrombotic events and 20 healthy controls. The study showed that, taking into account the concomitant anticoagulant treatment, Staclot LA was positive only in the propositus, raising the suspicion of a possible aPL-related origin of the thrombotic event. This issue was definitively confirmed in a subsequent follow-up. Conclusion The present report shows that aPL-related deep vein thrombosis can be the earliest clinical manifestation of pediatric SLE, and that Staclot LA may have a role in LA detection during the course of anticoagulant treatment. Received: 6 October 1998 / Accepted: 15 September 1999     

Laparoscopic removal of a persistent Müllerian duct in a male: case report.

The authors refer to the use of the laparoscopic approach in Persistent Mullerian Duct Syndrome, starting from a case of "male vagina" with an anomaly inserted left ductus deferens inside the mullerian persistent duct. This patient was operated on using the laparoscopic technique.