Experimental acute pancreatitis induced by platelet activating factor in rabbits.

This study indicates that a single injection of platelet activating factor (PAF, 50-500 ng) into the superior pancreaticoduodenal artery of rabbits induces dose-dependent morphologic alterations of pancreatic tissue and increases serum amylase levels, both consistent with the development of an acute pancreatitis. The main histologic findings observed by light microscopy 24-72 hours after the injection of PAF were edema, polymorphonuclear neutrophil infiltration, cell vacuolization, and acinar cell necrosis. Fat cell necrosis was present in 30% of animals. By electron microscopy an increase of the number of zymogen granules in the apical region of acinar cells was observed 3 hours after PAF challenge. At 24-72 hours, many acinar cells showed vacuoles containing myelinlike figures, zymogen granules, and cellular debris. Pancreatic lesions developed in the area supplied by the artery injected with PAF and they were completely antagonized by the pretreatment of rabbits with CV 3988, a specific antagonist of PAF. In addition, the significant protective effect of atropine suggests a potential role for cholinergic mechanisms in the pancreatic alterations induced by PAF

Relationship between neuroendocrine features and prognostic parameters in human prostate adenocarcinoma.

PURPOSE: The biological behaviour of prostate cancer is highly variable and prediction by the commonly employed prognostic parameters is not sufficient. The concept of neuroendocrine (NE) differentiation in prostate adenocarcinoma has recently received increasing attention due to possible implications for prognosis and therapy. MATERIALS AND METHODS: Core needle biopsies from 142 newly diagnosed patients were immunohistochemically examined for the coexistence of NE differentiation using an antibody against chromogranin A (CgA). Circulating CgA was available in 106 of these patients. RESULTS: NE differentiation was found in 64 (45.1%) tumors. Among them 29 (20.4%) had CgA positive cells scattered or focally distributed in less than 5% per mm3 of tumor tissues, 26 (18.3%) between 5% and 10% and 9 (6.4%) more than 10%, respectively. There was a significant correlation between the extent of NE features and either Gleason score (P < 0.01) or stage of disease. Circulating CgA but not PSA correlated with immunohistochemical CgA (P < 0.03) particularly in metastatic cases. CONCLUSIONS: These data support the concept that NE differentiation in human prostate cancer has a negative prognostic significance. Circulating CgA levels reflect immunohistochemical findings

Effect of total androgen ablation on pathologic stage and resection limit status of prostate cancer. Initial results of the Italian PROSIT study.

The likelihood of finding organ-confined untreated prostate cancer (PCa) by pathological examination at the time of radical prostatectomy (RP) is only 50% in patients with clinically organ-confined disease. In addition, tumour is present at the resection margin in approximately 30% of clinical T2 (clinical stage B) cases. The issue of clinical "understaging" and of resection limit positivity have led to the development of novel management practices, including "neoadjuvant" hormonal therapy (NHT). The optimal duration of NHT is unknown. We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total androgen ablation either for three or six months before RP. Between January 1996 and February 1998, 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian randomised prospective PROSIT study. Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status. By February 1998, haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the reviewing pathologist (RM). 64 cases had not been treated with total androgen ablation (e.g. NHT) before RP was performed, whereas 58 and 33 had been treated for three and six months, respectively. 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total androgen ablation, pathological stage B was more prevalent among patients with clinical B tumours, compared with untreated patients (57% in treated patients vs. 36% in untreated). The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone (69% vs. 42%, respectively). After six months of NHT therapy the proportion of patients with pathological stage B (67% vs. 36%, respectively) and negative margins was greater than after 3 months (92% vs. 42%, respectively). For clinical C tumours, the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours, when compared with the untreated group (pathological stage B: 31% and 33% vs. 6% in the clinical C cases, respectively. Negative margins: 56% and 67% vs. 31%, respectively). The initial results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage B because of the significant pathological downstaging and decrease in the number of positive margins in the RP specimens. These two effects are more pronounced after six months of NHT than after three months of therapy. The same degree of beneficial effects are not observed in clinical C tumours