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Retroperitoneal lymph node dissection (RPLND) is the most accurate method to evaluate the presence and extent of retroperitoneal nodal metastases in clinical stage I non-seminomatous germ cell testicular carcinoma. In our Department the open "nerve sparing" RPLND is already the standard surgical treatment for these tumors and laparoscopic technique is employed in surgical treatment of digestive diseases as cholelithiasis, hiatal hernias and gastrointestinal tumors; we report our first experience with laparoscopic RPLND in patients with low stage non-seminomatous germ cell testicular tumors (NSGCTT). A laparoscopic modified template RPLND was performed in 5 high-risk patients with non-seminomatous germ cell clinical stage I tumors by a transperitoneal approach. In 4 of the 5 cases a template dissection was performed. In one pathological stage II tumor a limited lymph node dissection was performed and the patient underwent postoperative chemotherapy. Mean operative time was 190 minutes (range 160-210). No retrograde ejaculation occurred. The mean number of dissected nodes was 21 (range 16-25). At mean follow-up of 16.3 months (range 12-21) the 4 operated patients with pathological stage I NSGCTT are disease free without ejaculatory or urinary dysfunction. Our preliminary experience suggests that laparoscopic RPLND for stage I NSGCTT is feasible and safe for surgeons largely trained in either laparoscopic digestive surgery or open RPLND for whom the learning curve of that minimally invasive approach is lower than expected.

The small cell carcinoma is a neuroendocrine tumour characterised by an aggressive clinical course and a high mortality rate. It occurs most commonly in the lung. Small cell carcinomas originating in the genitourinary system have been diagnosed with increasing frequency in recent years, because of the use of immunohistochemistry. Prostatic small cell carcinomas present the same biological behavior and similar histological, immunohistochemical and ultrastructural features to small cell carcinomas of the lungs. We describe the clinico-pathological findings in a 65-year-old male patient with a diagnosis of prostatic small cell carcinoma, obtained by means of a tru-cut needle biopsy. We performed the immunohistochemical tests using neuron-specific enolase and chromogranin A antibodies, according to the literature. On the basis of our experience we stress the malignant features of small cell carcinoma and the difficulty in obtaining an early diagnosis and treatment because of the aggressive course of the lesion and the late symptomatology.

The possibility of reducing the incidence of postoperative recurrences of pilonidal fistulas by using preoperative doses of Cephoxitine and primary surgical closure is described.

Mitogen-activated protein (MAP) kinases have a central role in several biological functions, including cell adhesion and spreading, chemotaxis, cell cycle progression, differentiation, and apoptosis. Extracellular signal-regulated kinase 8 (Erk8) is a large MAP kinase whose activity is controlled by serum and the c-Src non-receptor tyrosine kinase. Here, we show that RET/PTC3, an activated form of the RET proto-oncogene, was able to activate Erk8, and we demonstrate that such MAP kinase participated in RET/PTC3-dependent stimulation of the c-jun promoter. By using RET/PTC3 molecules mutated in specific tyrosine autophosphorylation sites, we characterized Tyr(981), a known binding site for c-Src, as a major determinant of RET/PTC3-induced Erk8 activation, although, surprisingly, the underlying mechanism did not strictly depend on the activity of Src. In contrast, we present evidence that RET/PTC3 acts on Erk8 through Tyr(981)-mediated activation of c-Abl. Furthermore, we localized the region responsible for the modulation of Erk8 activity by the RET/PTC3 and Abl oncogenes in the Erk8 C-terminal domain. Altogether, these results support a role for Erk8 as a novel effector of RET/PTC3 and, therefore, RET biological functions.

Histone deacetylases (HDACs) are key regulatory enzymes involved in the control of gene expression and their inhibition by specific drugs has been widely correlated to cell cycle arrest, terminal differentiation, and apoptosis. Here, we investigated whether HDAC activ- ity was required for PDGF-dependent signal transduction and cellular proliferation. Exposure of PDGF-stimulated NIH3T3 fibroblasts to the HDAC inhibitor trichostatin A (TSA) potently repressed the expression of a group of genes correlated to PDGF-dependent cel- lular growth and pro-survival activity. Moreover, we show that TSA interfered with STAT3-dependent transcriptional activity induced by PDGF. Still, neither phosphorylation nor nuclear translocation and DNA-binding in vitro and in vivo of STAT3 were affected by using TSA to interfere with PDGF stimulation. Finally, TSA treatment resulted in the suppression of PDGF-dependent cellular prolif- eration without affecting cellular survival of NIH3T3 cells. Our data indicate that inhibition of HDAC activity antagonizes the mitogenic effect of PDGF, suggesting that these drugs may specifically act on the expression of STAT-dependent, PDGF-responsive genes.

Pro-inflammatory cytokines, environmental stresses, as well as receptor tyrosine kinases regulate the activity of JNK. In turn, JNK phosphorylates Jun members of the AP-1 family of transcription factors, thereby controlling processes as different as cell growth, differentiation, and apoptosis. Still, very few targets of the JNK-Jun pathway have been identified. Here we show that JNK is required for the induction of c-myc expression by PDGF. Furthermore, we identify a phylogenetically conserved AP-1-responsive element in the promoter of the c-myc proto-oncogene that recruits in vivo the c-Jun and JunD AP-1 family members and controls the PDGF-dependent transactivation of the c-myc promoter. These findings suggest the existence of a novel biochemical route linking tyrosine kinase receptors, such as those for PDGF, and c-myc expression through JNK activation of AP-1 transcription factors. They also provide a novel potential mechanism by which both JNK and Jun proteins may exert either their proliferative or apoptotic potential by stimulating the expression of the c-myc proto-oncogene.