High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?

AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS: The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.     

Mesenteric vein thrombosis after surgery and radiotherapy for pancreatic carcinoma. A case report

A case is reported of a 54-year-old female patient undergoing the resection of a pancreatic carcinoma with intraoperative radiation therapy (10 Gy) on the tumor bed and subsequent external beam radiotherapy (50 Gy). After surgery the patient presented chronic diarrhea resistant to oral pancreatic enzymes. Twenty-five months postoperatively, mesenteric vein thrombosis was diagnosed after an episode of melena and was treated with conservative therapy. At five-year follow-up the patient had no evidence of neoplastic disease and bowel movements had increased. On imaging examinations, the presence of venous collaterals and cavernous appearance of the portal trunk were documented.     

Radiation therapy of breast cancer. Reasoned approach to a clinical case

The case of a patient undergoing quadrantectomy of lower quandrants of the right breast and ipsilateral axillary lymph node dissection for breast cancer followed by adjuvant radiotherapy is discussed. The stage of the disease and prognostic factors are analyzed for prognosis. Comorbidities ruled out chemotherapy. Radiation therapy was planned followed by clinicoinstrumental controls. After the second control ipsilateral costal bone metastases were observed; radiation therapy for palliation was prescribed.     

The endocytotic pathway is required for increased A beta 42 secretion during apoptosis

Secretion and progressive cerebral accumulation of beta-amyloid peptides (A beta), which derive by endoproteolytic ('amyloidogenic') processing of beta-amyloid precursor protein (APP), are felt to represent collectively an early and necessary event in the pathogenesis of Alzheimer's disease. APP amyloidogenic processing can occur via secretory or endocytotic pathways, but the relative contribution of these pathways to A beta secretion remains to be established. The effect of apoptosis on amyloidogenic processing and A beta secretion similarly is incompletely understood. We tested the hypothesis that APP processing by the endocytotic pathway represents a stress-related neural cell response, by comparing A beta secretion after induction of apoptosis in PC12 cells transfected either for endocytosis-competent or -deficient APP. Newly prepared adenoviral vectors encompassing targeted mutagenesis of the cytoplasmic tail YENP tetrapeptide sequence, which serves as the principal APP internalization signal, were used to express endocytosis-deficient holoprotein. We report that the endocytotic pathway is required for the generation and secretion of A beta 42, and that secretion of this neurotoxic peptide increases significantly during apoptosis. We demonstrate additionally that more A beta 40 apparently is generated in secretory compartments during apoptosis when APP processing by the endocytotic pathway is impaired.     

Regulation of squamous cell carcinoma antigen production by E-cadherin mediated cell-cell adhesion in squamous cell carcinoma cell line

Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and management of squamous cell carcinoma. It is well known that cell-cell adhesion is important for progression of cancer. However, it is not clarified whether cell-cell adhesion affects SCCA production in squamous cell carcinoma. The present study was, therefore, undertaken to investigate whether E-cadherin-mediated cell-cell adhesion affects SCCA production in squamous cell carcinoma of the uterine cervix. SKG-IIIa cells or CaSki cells, cervical squamous cell carcinoma cell lines, were treated with anti-E-cadherin antibodies (1 microg/ml) up to 72 h. The cells were dissociated, and SCCA content in the cytosol and SCCA mRNA levels were significantly decreased compared to the control group treated with mouse IgG. Secondly, the signaling pathway for SCCA production mediated by E-cadherin was examined. Phosphatidylinositol (PI) 3-kinase is a well-known mediator of E-cadherin-mediated biological events. The treatment with a PI 3-kinase inhibitor suppressed SCCA production in SKG-IIIa cells. It is concluded that E-cadherin mediated cell-cell adhesion maintains SCCA production through PI 3-kinase in squamous cell carcinoma.     

Bronchopulmonary foregut malformation: a large bronchogenic cyst communicating with an esophageal duplication cyst

A 1-year-old boy with a bronchopulmonary foregut malformation presented with a large mediastinal bronchogenic cyst associated with pulmonary sequestration, a cervical esophageal duplication cyst, a bronchial communication between these cysts, and 2 small bronchogenic cysts around the communication. These lesions were resected followed by an uneventful recovery. J Pediatr Surg 38:E2.     

Direct Observation of the Enthalpy Relaxation and the Recovery Processes of Maltose-Based Amorphous Formulation by Isothermal Microcalorimetry

Purpose. The applicability of isothermal microcalorimetry (IMC) for evaluating enthalpy relaxation and recovery processes of amorphous material was assessed. Methods. A maltose-based formulation was prepared by freeze-dry method. Differential scanning calorimetry (DSC) was used to investigate its glass transition and relaxation behaviors. IMC was applied to quantitatively analyze the relaxation and the recovery processes. The IMC data were analyzed using a derivative of the Kohlrausch-Williams-Watts equation. Results. The glass transition temperature of the formulation and its fictive temperature stored at 15°C for 1 year were 62 and 32°C, respectively. DSC study showed that annealing below the fictive temperature increased the enthalpy recovery, but it was decreased by annealing at higher temperatures. IMC enabled direct observation of the heat flow during both the relaxation and the recovery processes. The decay constant for the recovery process (recovery time) was much smaller and less sensitive to the temperature than that for the relaxation process (relaxation time). Conclusions. IMC was successfully used to obtain quantitative information on both relaxation and recovery processes of amorphous material. The relaxation parameters obtained by this method could explain the thermodynamic behavior of the formulation.     

Virtual simulation: fifteen years later

In the last two decades there was a radical change in radiotherapy setup. The growing availability of CT equipment and console for computer-aided treatment planning setup enabled the use of advanced technologies as conformal 3D radiation therapy in most centers. In particular in 1987 virtual simulation was proposed for setup. During its use a number of application modalities appeared. Virtual simulation in some centers is applied alone while in others it is associated with conventional simulation. However, from numerous reports published in last years it seems that virtual simulation significantly improves treatment quality independently of radical or palliative intent and of the size of treated volumes (high doses to small volumes or wide shaped fields). Some studies stressed that virtual simulation could significantly shorten treatment planning times with consequent cost reduction. The use of virtual simulation evidenced associated problems and in particular setup limitations due to the CT gantry size, the need to up-date the conventional modalities of setup verification according to the new technologies and more generally to up-date quality assurance procedures in an advanced technological setting. Finally there was the self-evident need of a better knowledge of the anatomy on axial sections, of tumor spread routes in particular.     

Clinical application of extracorporeal shock wave lithotripsy to 5 solitary kidney patients with upper urinary tract stones

We performed extracorporeal shock wave lithotripsy (ESWL) to 5 solitary kidney patients with upper urinary tract stones (4 kidneys and 1 lower ureter) using the EDAP lithotripter LT-01 and achieved 4 complete and 1 well results. The size of stones ranged from 8 mm to staghorn and trials were 1 to 10 units. We could accomplish perfect crushing and abortion of stones in the 4 renal stone patients without any adjuvant systems as ureteral stent but nephrostomy was needed in the 1 lower ureteral stone patient developed anuria. The values of blood pressure, hematology, blood chemical constituents and urine excretion enzymes at a month after the last ESWL were not so changed compared with those of preoperation and also excretory urogram showed favorable findings. In this series decreased renal functions by ESWL were not observed. We confirmed ESWL was an effective and a safe method even in the cases of solitary kidney patients and monotherapy without any adjuvants was possible.     

A case of primary malignant neoplasms associated with penile cancer and prostatic cancer

A case of a 79-year-old man with penile cancer and prostate cancer is reported. The pathological study of surgical specimens disclosed well-differentiated squamous cell carcinoma of the penis and poorly differentiated adenocarcinoma of the prostate. This is a rare case of multiple primary malignant neoplasms associated with penile cancer and prostate cancer.