Expression of c-erb B-2 oncogene product in persistent gestational trophoblastic disease

OBJECTIVE: Much debate exists on the initiation of chemotherapy for women at risk for persistent gestational trophoblastic disease. This is a result of a lack of early predictors for the development of persistent gestational trophoblastic disease after evacuation of a complete hydatidiform mole, because the only current reliable method of detection and diagnosis lies in persistent or rising postmolar β-human chorionic gonadotropin values. We used immunocytochemical techniques to retrospectively study the expression of the c-erb B-2 oncogene product in formalin-fixed, paraffin-embedded trophoblastic tissues as a potential indicator of the development of persistent gestational trophoblastic disease. STUDY DESIGN: In this retrospective study 56 trophoblastic tumors were examined by means of immunocytochemical techniques to stain for the oncogene product for evidence of c-erb B-2 expression. Our 56 cases included original tissue from 20 cases of complete mole that progressed to persistent gestational trophoblastic disease, seven cases of choriocarcinoma after term pregnancy or abortion, and 29 cases of hydatidiform mole representing postevacuation, spontaneously regressing disease (including one partial mole). We also studied 11 cases of first-trimester trophoblast and 15 cases of term placenta as additional controls. RESULTS: Our results showed positive immunostaining for c-erb B-2 gene product in one case of persistent gestational trophoblastic disease, with negative staining in all other cases in the study groups and controls. CONCLUSION: Analysis for the significance of c-erb B-2 expression in persistent gestational trophoblastic disease showed that this correlation between c-erb B-2 expression and persistent gestational trophoblastic disease is not significant, suggesting that future efforts should be directed at the involvement of different oncoproteins. (AM J Obstet Gynecol 1994;170:1616-22.)     

The use of intraoperative radiation therapy in radical salvage for recurrent cervical cancer: Outcome and toxicity

Objective: Our purpose was to evaluate the contribution of intraoperative radiation therapy in the management of recurrent cervical cancer.Study design: Twenty-two patients were treated with electron beam intraoperative radiation therapy for recurrent cervical cancers that were confined to the pelvis but were too extensive to be adequately treated by radical surgery alone. All patients underwent extensive surgical dissection for exposure and maximal tumor resection. Doses of intraoperative radiation therapy ranged from 14 to 27.8 Gy (median 22 Gy). Twelve patients received intraoperative radiation therapy to address gross residual disease, and 10 patients were treated for microscopically positive or close surgical margins.Results: The five-year disease-specific survival and local control rates were 43% and 48%, respectively. There were trends toward better local control and disease-specific survival in patients with microscopic residual disease compared with those with gross residual disease. Seven patients had peripheral neuropathy related to treatment, and four of these cases resolved.Conclusion: In carefully selected cases intraoperative radiation therapy contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall.     

Superficially invasive vulvar cancer with nodal metastases

Seven patients with superficially invasive vulvar cancer and lymph node metastases are reported. Histology of the primary tumor does not seem to correlate reliably with its metastatic potential in any individual case, though “spray,” pseudoglandular, and small cell carcinomas may be particularly aggressive lesions. While wide local excision seems to be adequate treatment for the primary lesion, it is recommended that for lesions with greater than 1 mm of stromal invasion, bilateral inguinal-femoral lymphadenectomy should be performed for midline lesions, and at least ipsilateral inguinal-femoral lymphadenectomy should be performed for lateralized lesions.     

Long-Term Results of Infrageniculate Bypass Grafting Using All-autogenous Composite Vein

Infrageniculate (below-knee) bypass using all-autogenous composite vein requires multiple incisions, venovenostomy, and prolonged operating time. The purpose of this study was to evaluate the long-term results of this procedure, with comparisons to grafts created from single-segment greater saphenous vein (GSV) or polytetrafluoroethylene (PTFE). A total of 362 consecutive infrainguinal bypass grafts with infrageniculate distal target arteries were created in 283 patients in a single institution between January 1995 and December 2000. Comorbid conditions were common, including diabetes (58%), coronary artery disease (56%), prior lower extremity revascularization (41%), end-stage renal failure (20%), and prior coronary artery bypass grafting (18%). The indication for revascularization was limb salvage in 93% of cases. The grafts were constructed from single segments of GSV (n = 239), from two or more vein segments resulting in an all-autogenous composite graft (n = 61), or from PTFE (n = 62). All-autogenous composite grafts were constructed using segments of ipsilateral or contralateral GSV (n = 49), upper extremity vein (n = 23), superficial femoral vein (n = 7), or lesser saphenous vein (n = 5). Infrageniculate all-autogenous composite vein grafts exhibited similar long-term results to those of GSV grafts, and far superior results to those of PTFE grafts. For patients with available autogenous segments, the all-autogenous composite vein graft is the conduit of choice.     

Laparoscopic varicocelectomy for painful varicoceles: merits and outcomes

PURPOSE: To evaluate the effectiveness of laparoscopic ligation as an option offered to patients with painful varicocele. Laparoscopy has been an established technique for varicocelectomy in infertile patients, but little objective data exist addressing its effectiveness in the control of pain. PATIENTS AND METHODS: We reviewed records of 68 patients who underwent laparoscopic varicocelectomy for pain from March 1988 through March 2000. We documented patient age at operation, grade and side of the varicocele, duration and quality of the pain, and response to conservative treatment and laparoscopic ligation. RESULTS: Follow-up data were available for 58 patients. Their average age was 21.5 years (range 14-39 years). The varicocele was left sided in 51 patients and bilateral in 7. Forty patients described their pain as dull or throbbing ache and 13 as a dragging sensation, while 5 patients were unable to characterize their pain. Initial conservative treatment failed in all patients. Varicocele was grade III in 29 patients, grade II in 27, and grade I in 2. In 49 patients (84.5%), there was complete postoperative resolution of pain, while 6 (10.3%) had partial resolution. Only three patients had persistent symptoms. Hydrocele formation occurred in 3 patients (5.2%), and varicocele persisted in 2 (3.4%). CONCLUSIONS: This retrospective review supports varicocele ligation for the relief of pain. Laparoscopic ligation is an effective and safe approach to achieve this outcome.     

Differential mechanical activation of mitogen-activated protein kinases in intact human blood vessels

BACKGROUND: Vascular tissue remodels in response to a variety of hemodynamic factors, often transduced through activation of mitogen-activated protein kinases such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase (JNK). This study tests the hypothesis that these kinases are involved in mechanical signal transduction in intact human arteries and veins. METHODS: Unused portions of human saphenous vein and radial artery were obtained fresh at the time of peripheral or coronary bypass. A sample of the vessel was immediately snap frozen (control(0)) and the remainder separated into three segments. One segment was placed in sterile medium and left undisturbed for 2 h (control(2)), one was perfused with sterile medium for 2 h at a steady rate of 150 ml/min, yielding shear stress values of 8-20 dyne/cm(2) (flow), and one was statically pressurized without flow at 110 mm Hg for 2 h (pressure). After treatment, samples were tested for phosphorylated ERK1/2 and JNK using Western blot. RESULTS: Two hours of culture produced mild increases in ERK1/2 activity in both vessel types. Stimulation with continuous rapid flow produced significantly increased ERK1 activity and a nearly 100% increase in ERK2 in veins. Static pressurization also stimulated ERK1/2, although slightly less than continuous flow. ERK1/2 phosphorylation was only mildly increased in flow-stimulated radial arteries, and exposure to normal systemic pressure showed no appreciable effect. Significant phosphorylation of JNK was not observed in either vessel. CONCLUSION: ERK1/2 phosphorylation is increased in human saphenous veins and radial arteries exposed to the hemodynamic conditions of arterial grafting. This pathway may be involved in the transduction of external stimuli leading to remodeling.     

Soy-based formulae and infant growth and development: a review

Soy-based infant formulae, initially developed for infants who were lactose intolerant or allergic to cow's milk-based formulae, now account for >25% of the infant formulae sold in the United States. Formulations have changed over the years to improve digestibility, the stability and availability of minerals, and protein quality. Recent concerns have been raised regarding the phytoestrogenic isoflavone content of soy-based formulae. A systematic review of the literature was conducted to evaluate various measures of infant health and development in clinical studies comparing modern soy-based formulae with other diets and to document areas in which further research seems warranted. Results suggest that modern soy-based formulae support normal growth and nutritional status in healthy term infants in y 1 of life. However, there are very limited data on sexual and reproductive development or outcomes such as immune function, visual acuity/cognitive development and thyroid function. Available data do not provide evidence of meaningful differences in timing of maturation, sexual development or fertility in adolescents or adults. Nonetheless, given evidence suggesting that early exposure to soy and/or isoflavones might have long-term effects, further research following infants fed soy-based formulae into adulthood is warranted.     

Differences in peripheral nerve degeneration/regeneration between wild-type and neuronal nitric oxide synthase knockout mice

Nitric oxide (NO), a unique biological messenger molecule, is synthesized by three isoforms of the enzyme NO synthase (NOS) and diffuses from the site of production across cellular membranes. A postulated role for NO in degeneration and regeneration of peripheral nerves has been explored in a sciatic nerve model comparing wild-type mice and mice lacking neuronal NOS after transection and microsurgical repair. In NOS knockout mice, regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). In the regenerated nerve, pruning of uncontrolled sprouts was disturbed, leading to an enhanced number of axons, whereas remyelination seemed to be less affected. Delayed regeneration was associated with a delayed recovery of sensor and motor function. In such a context, possible NO targets are neurofilaments and myelin sheaths of the interrupted axon, filopodia of the growth cone, newly formed neuromuscular endplates, and Schwann cells in the distal nerve stump. The results presented suggest that 1) local release of NO following peripheral nerve injury is a crucial factor in degeneration/regeneration, 2) success of fiber regeneration in the peripheral nervous system depends on a regular WD, and 3) manipulation of NO supply may offer interesting therapeutic options for treatment of peripheral nerve lesions.