Search

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. 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. 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. 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.

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. 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). 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. 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.

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. J. Cell. Physiol. 226: 1099–1109, 2011. © 2010 Wiley-Liss, Inc.

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.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.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 (P0.05). 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 (P0.05). 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 (P0.05). 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.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.

Rhabdomyolysis is a rare complication of serious surgical procedures, and constitutes a clinical and biochemical syndrome, caused by injury and destruction of skeletal muscles. It is accompanied by pain in the region of the referred muscle group, increase in creatine phosphokinase levels, myoglobinuria, often with severe renal failure, and finally multi-organ system failure and death, if not treated in time. The main risk factor in the development of postoperative rhabdomyolysis is prolonged intraoperative immobilization of the patient. Morbidly obese patients who undergo laparoscopic bariatric operations should be considered high-risk for rhabdomyolysis, from extended immobilization and pressure phenomena in the lumbar region and gluteal muscles. We report a 20-year-old woman with BMI 51, who underwent a prolonged laparoscopic Roux-en-Y gastric bypass. Postoperatively, she presented severe myalgia in the gluteal muscles and lumbar region, oliguria and creatine phosphokinase levels that reached 38,700 U/L. She was treated with intensive hydration and analgesics, and did not develop acute renal failure because diagnosis and treatment were attained immediately.

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. Eur J Radiol

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.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.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.The presence of the M541L KIT variation in MCC warrants further studies for its role in the pathogenesis of this tumor.

PURPOSE: We report our 5-year experience in the management of ureteral stones in pediatric patients using shockwave lithotripsy (SWL) in combination with ureteroscopy. PATIENTS AND METHODS: A total of 25 children (age range 12 months-14 years; mean 8.7 years) underwent SWL for ureteral lithiasis. Stones were located in the upper ureter in 6 children (24%), the middle ureter in 8 (32%), and the lower ureter in 11 (44%). Their size ranged from 5 to 14 mm (mean 10.9 mm). The children who failed SWL underwent ureteroscopic treatment. RESULTS: In the SWL-only group, the overall stone clearance rate at 3 months was 84% (21 of 25 children). Four children (16%) who failed SWL underwent successful ureteroscopic treatment. Complications were infrequent and generally minor in both groups. CONCLUSIONS: Shockwave lithotripsy is a safe and efficient treatment modality for ureteral stones in pediatric patients. In expert hands, ureteroscopy can be successfully applied in case of SWL failure. J Endourol

OBJECTIVE: We report our experience on intraureteral metallic stents placement for the treatment of malignant and benign ureteral strictures. METHODS: Eight patients (six men and two women) with inoperable malignant or benign ureteral strictures, underwent insertion of metallic stents through percutaneous tracts. Six lesions (three malignant, three benign) involved ureterointestinal anastomoses after cystectomy for bladder cancer and ureteroileal urinary diversion or bladder substitution, and two malignant lesions involved the midureter. Self-expandable stents were used in seven cases and a balloon-expandable stent in the remaining one case. One stent was sufficient in seven ureters, and in one ureter, two overlapping stents were placed. RESULTS: Metallic stents were inserted without technical difficulties in all obstructed ureters and patency was achieved in all patients. Ultrasonography revealed resolution of pre-existing hydronephrosis. The duration of follow-up was 6-17 months (mean, 9 months). One ureter was occluded 8 months after stent placement because of ingrowth of tumor and granulation tissue. The other ureters showed no signs of obstruction during follow-up. No major complications directly attributable to the metallic stent occurred. CONCLUSIONS: Our results suggest that insertion of a metallic stent in the ureter is feasible and safe for the treatment of benign or malignant ureteral strictures. However, more work needs to be done to establish the use of these stents for the treatment of ureteral obstruction. Eur J Radiol

Human glutamate dehydrogenase (GDH), an enzyme central to the metabolism of glutamate, is known to exist in housekeeping and nerve tissue-specific isoforms encoded by the GLUD1 and GLUD2 genes, respectively. As there is evidence that GDH function in vivo is regulated, and that regulatory mutations of human GDH are associated with metabolic abnormalities, we sought here to characterize further the functional properties of the two human isoenzymes. Each was obtained in recombinant form by expressing the corresponding cDNAs in Sf9 cells and studied with respect to its regulation by endogenous allosteric effectors, such as purine nucleotides and branched chain amino acids. Results showed that L-leucine, at 1.0 mM:, enhanced the activity of the nerve tissue-specific (GLUD2-derived) enzyme by approximately 1,600% and that of the GLUD1-derived GDH by approximately 75%. Concentrations of L-leucine similar to those present in human tissues ( approximately 0.1 mM:) had little effect on either isoenzyme. However, the presence of ADP (10-50 microM:) sensitized the two isoenzymes to L-leucine, permitting substantial enzyme activation at physiologically relevant concentrations of this amino acid. Nonactivated GLUD1 GDH was markedly inhibited by GTP (IC(50) = 0.20 microM:), whereas nonactivated GLUD2 GDH was totally insensitive to this compound (IC(50) > 5,000 microM:). In contrast, GLUD2 GDH activated by ADP and/or L-leucine was amenable to this inhibition, although at substantially higher GTP concentrations than the GLUD1 enzyme. ADP and L-leucine, acting synergistically, modified the cooperativity curves of the two isoenzymes. Kinetic studies revealed significant differences in the K:(m) values obtained for alpha-ketoglutarate and glutamate for the GLUD1- and the GLUD2-derived GDH, with the allosteric activators differentially altering these values. Hence, the activity of the two human GDH is regulated by distinct allosteric mechanisms, and these findings may have implications for the biologic functions of these isoenzymes.