Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma.

In somatostatinoma, a rare malignant somatostatin (SST)-secreting neoplasia, tumour regression is rarely observed, implying the need for novel antiproliferative strategies. Here, we characterized a long-term culture (SST-secreting cancer (SS-C cells)) established from a human somatostatinoma. High concentrations of SST and chromogranin A were released by SS-C cells and SST release was stimulated by depolarizing stimuli and inhibited by the SST analogue, octreotide. SS-C cells expressed mRNA for SST receptor (SSTR) subtypes 1, 2 and 4, being also able to bind native SST. Moreover, SS-C cells were positively stained with an antibody to SSTR2. SS-C cells also expressed interferon-gamma (IFN-gamma) receptor mRNA and measurable telomerase activity. Our findings indicate that in vitro exposure of SS-C cells to native SST-28, to octreotide, to IFN-gamma, or to 3'-azido-3'deoxythymidine (AZT), a telomerase inhibitor, results in inhibition of SS-C cell proliferation. Concomitant with growth inhibition, apoptosis was detected in SST-, octreotide-, IFN-gamma- or AZT-treated SS-C cell cultures. Taken together our results characterized native SST, SST analogues, IFN-gamma and a telomerase inhibitor as growth-inhibiting and proapoptotic stimuli in cultured human somatostatinoma cells. Based on these findings, the potential of SST analogues, IFN-gamma and AZT, alone or in combination, should be further explored in the medical treatment of somatostatinoma.

[Rectal cancer: locoregional recurrence in relation to surgical and complementary treatment]. / Il cancro del retto: le recidive locoregionali in rapporto alle terapie chirurgiche e complementari adottate.

Much recent data have been published on the risk of local recurrence (LR) following curative surgery for rectal cancer and the impact of adjuvant therapy. On the other hand, improvements in surgical techniques, as the total mesorectal excision, have apparently reduced the risk of LR. Furthermore, in selected cases, neoadjuvant therapy seems to reduce much more the incidence of LR. A list of prognostic factors which affect the onset of LR, other than the different procedures, was considered. To investigate such evidences a retrospective analysis was undertaken in our series, focusing on examination of the employed techniques as potential predictors of local recurrence. Thus, in a 18-yr-period (1986-2003), two hundred and ninety-five patients who had undergone elective curative surgical resection of rectal cancer were included in the study. The demographic, operative and follow-up data were collected retrospectively. All patients underwent total mesorectal excision, whereas neoadjuvant therapy was performed in a selected series of patients, according to defined entry criteria patterns. Results evidenced LR in 7.1% of patients and occurred between 6 months to 8 year following surgery. Comparisons were made between patients who had different surgical procedures; indeed sphyncter saving procedures correlated with a higher incidence of LR rather than abdomino-perineal resection. Pelvic recurrences were observed more frequently compared to the anastomotic ones. A limited number of patients with LR underwent surgery due to the associated condition of metastatic lesions; the follow-up related to such series evidenced a mortality rate of 57% within 3 year from reoperation. A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest that preoperative radiotherapy may be employed only for those patients who are at a higher risk for local recurrence.