Complications and toxicity after abdominal and pelvic hypoxic stop-flow perfusion chemotherapy: incidence and assessment of risk factors.

BACKGROUND: Controversial results regarding the efficacy and toxicity of hypoxic abdominal and pelvic stop-flow perfusion chemotherapy (SFP) have been reported in relatively small series. Hence, because adequate assessment of its benefit in large homogenous cohorts is missing, acceptable morbidity should initially be assured in a series of adequate size. Additionally, risk factors should be assessed for eventual patient selection. METHODS: The morbidity of abdominal and pelvic SFP performed on a miscellaneous group of patients in our institute was analyzed and potential risk factors for adverse events were evaluated. RESULTS: Seventy abdominal (n = 42) and pelvic (n = 28) SFP were performed on 55 patients. In total, 28 adverse effects were observed after 30% of the procedures. Severe (grade 3) adverse events were recorded only after 4% of the procedures, while treatment-related life-threatening events and deaths were not present. Abdominal procedures when compared with pelvic ones were associated with increased systemic toxicity (36 vs. 7%, p = 0.005). Advanced age, gender, prior chemotherapy and/or radiotherapy, limited experience, repeated procedure, drug choice and omission of hemofiltration after SFP completion were not associated with statistically significant increase of procedures with overall or systemic adverse events. CONCLUSIONS: In the present series, abdominal and pelvic SFP was associated with an acceptable morbidity, which was mostly mild or moderate. Abdominal procedures were associated with increased toxicity. This procedure seems to be repeatable and also well tolerated both by elderly patients and by patients who had undergone prior chemotherapy and/or radiotherapy, while hemofiltration does not appear to decrease the incidence of systemic toxicity.

Identification of the M541L sequence variation of the transmembrane KIT domain in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive KIT-positive cutaneous tumor. KIT mutations are considered to play a key role in the pathogenesis of various neoplasms, but have not been found so far in MCC. The aim of the present study was therefore to investigate the presence of KIT mutations in MCC. MATERIALS AND METHODS: The entire coding region of KIT in the MCC cell line MCC-1 was sequenced. KIT exon 10 was amplified from archival paraffin-embedded MCC specimens by PCR and sequenced. RESULTS: Exon 10 M541L KIT sequence variation, which confers increased sensitivity to KIT ligand stem cell factor, was detected in the MCC-1 cell line. Sequencing of KIT exon 10 in six archival MCC specimens revealed the wild-type sequence. CONCLUSION: The presence of the M541L KIT variation in MCC warrants further studies for its role in the pathogenesis of this tumor.

Antiemetic prophylaxis in thyroid surgery: a randomized, double-blind comparison of three 5-HT3 agents.

PURPOSE: The aim of this double-blind randomized study was to compare the antiemetic efficacy of three 5-hydroxytryptamine type 3 antagonists in terms of the incidence and intensity of postoperative nausea and vomiting (PONV) in a homogenous group of female patients undergoing thyroidectomy. METHODS: The study cohort consisted of 203 American Society of Anesthesiologists PS I-II female patients randomized into four groups to receive at induction of anesthesia an intravenous (IV) bolus of 5 ml solution of one of the following: normal saline (placebo), granisetron 3 mg, ondansetron 4 mg, or tropisetron 5 mg. Nausea and vomiting were evaluated at five time points: during the first hour in the postanesthesia care unit (PACU) and 6, 12, 18, and 24 h postoperatively. Nausea intensity was measured using a visual analogue scale score (0-10). RESULTS: Patients in the placebo group displayed a high incidence of nausea in the PACU and at 6, 12, and 18 h postoperatively (44, 60, 50, and 34%, respectively) and of vomiting (26, 42, 30 and 10%). The administration of granisetron reduced significantly the incidence of nausea at 6, 12, and 18 h (26, 18, and 2%, respectively) and vomiting at 6 and 12 h (10 and 6%, respectively). Ondansetron reduced significantly the incidence of nausea and vomiting only at 6 h postoperatively (28 and 12%, respectively). The administration of tropisetron did not affect the incidence of PONV compared to placebo. CONCLUSION: Among the female patients of this study undergoing thyroid surgery, granisetron 3 mg provided the best prophylaxis from PONV. Ondansetron 4 mg was equally effective, but its action lasted only 6 h, whereas tropisetron 5 mg was found ineffective.

KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of merkel cell carcinoma in vitro.

The co-expression of KIT receptor and its ligand stem cell factor (SCF) has been reported in biopsy specimens of Merkel cell carcinoma (MCC). However, the functional role of SCF/KIT in the pathogenesis of this aggressive tumor has not been elucidated. The present study reports expression and effects of SCF and KIT in the Merkel cell carcinoma cell line MCC-1 in vitro. SCF and KIT were endogenously co-expressed in MCC-1 cells. Exogenous soluble SCF modulated KIT receptor mRNA and protein expression, stimulated growth of MCC-1 cells, upregulated endogenous activation of KIT, AKT, and of extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. On the contrary, an inhibitory antibody that neutralized the KIT ligand binding site, reduced growth of MCC-1 cells, as did high doses of the KIT kinase inhibitors imatinib and nilotinib. Also, inhibitors of KIT downstream effectors, U0126 that blocks MEK1/2 as well as wortmannin and LY294002 that inhibit phosphatidylinositol 3-kinase-dependent AKT phosphorylation, inhibited the proliferation of MCC-1 cells. These data support the hypothesis that KIT is activatable by paracrine or autocrine tumor cell-derived SCF and stimulates growth of Merkel cell carcinoma in vitro. Blockade of KIT and the downstream signaling cascade at various levels results in inhibition of Merkel cell carcinoma growth in vitro, suggesting targets for therapy of this cancer.

Sleeve gastrectomy-a "food limiting" operation.

BACKGROUND: Sleeve gastrectomy (SG), which, thus far, is showing good resolution of comorbidities and good weight loss, shows increasing popularity among bariatric surgeons. The aim of this study was to evaluate clinical outcome and the gastric emptying of solid foods, 24 months after SG. METHODS: Fourteen morbidly obese patients, four males and ten females, median age 41 years (range 29-65), median body mass index (BMI) 49.46 kg/m(2) (range 41.14-55.63), who underwent SG for weight loss, were studied prospectively. Nine patients underwent gastric emptying studies, using radioisotopic technique before, 6 months and 24 months after the operation. The remaining five patients underwent gastric emptying studies, 6 months and 24 months after the operation. RESULTS: A significant reduction in patients' weight and BMI was evident at 6, 12 and 24 months postoperatively. In the nine patients who underwent gastric emptying studies pre-, 6 and 24 months postoperatively, the T-lag phase duration significantly decreased, following the SG, from 17.30 (range 15.50-20.90) min, to 12.50 (range 9.20-18.00) min at 6 months and 12.16 (range 10.90-20.00) min at 24 months postoperatively (P < 0.05). The gastric emptying half time (T1/2) accelerated significantly postoperatively from 86.50 (range 77.50-104.60) min, to 62.50 (range 46.30-80.00) min at 6 months and 60.80 (range 54.80-100.00) min at 24 months after SG (P < 0.05). The percentage of gastric emptying (%GE) increased significantly postoperatively, from 52 (range 43-58) % to 72 (range 57-97) % at 6 months and 74 (range 45-82) % at 24 months, following SG (P < 0.05). No differences in gastric emptying were observed, when values at 24 months were compared to those at 6 months postoperatively. When the whole group of 14 patients was studied, there were also no significant changes in T-lag, T1/2 and %GE between 6 and 24 months postoperatively. CONCLUSIONS: Our study indicates the constant effect of SG in the acceleration of gastric emptying of solids, which occurs faster, not only in short but also in long-term postoperatively. Such effects on gastric motility, in combination with the reported alterations in gut hormones, may explain how this 'food limiting' operation results in weight loss.

Giant ureteral stone in association with primary megaureter presenting as an acute abdomen.

A 20-year-old woman presented with abdominal pain of 4-h duration and of sudden onset. A plain abdominal radiograph showed a giant ureteral stone measuring 12 cm causing ureteral obstruction. Abdominal ultrasound revealed severe dilatation of the two upper thirds of the left ureter and a hydronephrotic ipsilateral kidney. Subsequent renal scan demonstrated that it was a non-functional kidney while the contralateral kidney was normal. A left nephroureterectomy was performed.