Effects of type 5-phosphodiesterase inhibition on energy metabolism and mitochondrial biogenesis in human adipose tissue ex vivo.

OBJECTIVE: An excess of adipose tissue (AT) in obese individuals is linked to increased cardiovascular risk and mitochondria have been shown to be defective in the muscle and AT of patients with metabolic disorders such as obesity and Type 2 diabetes. Nitric oxide (NO) generated by endothelial NO synthase (eNOS) plays a role in mitochondrial biogenesis through cyclic-GMP (cGMP). AT harbors the whole molecular signaling pathway of NO, together with type 5-phosphodiesterase (PDE- 5), the main cGMP catabolising enzyme. AIM: Our aim was to evaluate the effect of the modulation of NO pathway, through PDE-5 inhibition, on energy metabolism and mitochondria biogenesis in human omental AT. METHODS AND MEASUREMENTS: Cultured human omental AT was stimulated with PDE-5 inhibitor, vardenafil, at different concentration for 24 and 72 h. Analysis of the expression of both key-regulator genes of adipocyte metabolism and mitochondria-biogenesis markers was performed. RESULTS: We found an increased gene expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), adiponectin, and proliferator- activated receptor gamma coactivator-1 α (PGC-1α) after a 24-h stimulation with vardenafil at the lowest concentration employed compared to controls (p<0.05). After 72 h of stimulation, a significant increase of mitochondrial DNA was found compared to control samples (p<0.05). CONCLUSION: Our data suggest that PDE-5 inhibition could have an impact on mitochondrial content of human AT suggesting a positive effect on energy metabolism and adding new elements in the comprehension of AT pathophysiology.

Complications, functional outcome and quality of life after intensive preoperative chemoradiotherapy for rectal cancer.

AIMS: To investigate early and late complications in 44 patients with locally advanced mid-low rectal cancer enrolled in a phase I-II study, who had received an aggressive chemoradiation treatment (50.4Gy/28F; 5-FU continuous infusion and weekly Oxaliplatin) followed by total mesorectal excision and 5-FU based postoperative chemotherapy. The aim of the present study is also to evaluate functional outcome and quality of life (QoL) in a sub-group of 22 patients. METHODS: Standardized forms for early and late surgical complications were completed for all patients. Anorectal function and QoL were also investigated in 22 patients who underwent surgery in the same surgical unit, using the fecal incontinence scoring system (FIS) and EORTC-QLQ-CR38 questionnaires, compiled before and after radiotherapy and at least 8 months after surgery. The differences over time in scores were analyzed using repeated measure ANOVA. RESULTS: The median age of patients (25 males and 19 females) was 58 (range: 34-73) years. A low anterior resection was performed in 39 cases, radical resection in 41, and 12 patients had a pathological complete response. There were no operative deaths; 4 and 9 patients required re-operation for early and late complications, respectively. FIS score did not present a significant worsening over time. According to data in the EORTC-QLQ-CR38 questionnaire, a significant improvement over time was found only for "future perspective". CONCLUSION: Our findings seem to indicate that this aggressive 5-FU-Oxalipaltin-based treatment implies no impairment of QoL and anorectal function, even if a high rate of late major complications was observed. Studies on larger series are required to confirm these results.

Palliative surgery for gastric cancer in elderly patients.

Poor survival rate of elderly patients affected by locally advanced or metastatic gastric cancer is related to primary tumour complications. Bleeding is the most important adverse event, other major complications are gastric outlet obstruction and nutritional deprivation. Rarely the patients will perforate the stomach cancer and there is a sudden end to their life; contamination of the ascites result in a rapid death. Thus, an aggressive approach toward palliation of this condition is resection: in this manner the expected survival is approximately one year. Derivation techniques or endoscopic treatments are applied in those patients whose operative risk is inacceptable; in these cases poor median survival is expected. The aim of this report in to refer about the experience in palliative surgery for gastric cancer in the Department of Geriatric Surgery of the University of Padua.

[Surgical risk in the elderly]. / Il rischio operatorio nell'anziano.

In our Country 16% of population is over 65 years old and on 2010 a quarter of people will be over 70 years old. More over the percentage of patients over 70 years admitted in surgical departments is triple than 10 years ago and the percentage of octgenarian patients is ten times. In the last years new methods of diagnosis and care have been introduced to reduce morbility and mortality; the preoperative evaluation to define the risk factors is complex. The surgeon should respect some primary points: the patient interest, true surgical treatments, multimodal management, valid pain therapy, discharge as soon as possible, ambulatory or day hospital management, expecting and quality of life.

[Septic shock: surgical and medical problems in the elderly]. / Shock settico: problematiche chirurgiche e mediche nell'anziano.

The sepsis is a bacterial invasion of the organism producing many manifestations which are able to amplify themselves. In the United States of America there are 100,000 death per year and the incidence is among 300,000-500,000 cases. The major surgery in the elder (especially if it is in emergency) has a great percental of risk because the preoperative study isn't often complete. Fever, agitation, panting, bullation, abdominal splinting, enteroplegia, are signals of evolving inflammatory situation. Moreover there are disorders of biochemical values: leukocytosis, thrombocytopenia, increased levels of VES, PCR, amylase and biliribinaemia. The more common radiological examinations are the straight radiography of abdomen and horax, abdomen ultrasonography, CT or MRI. In the last years pro-calcitonin, interleukin-6 , C-reactive protein, and nitric oxide from endothelial and muscularis cells have been evaluated as prognostic factors in the septic shock.

[Treatment of the early form of rectal carcinoma in the elderly]. / Il trattamento delle forme iniziali di carcinoma rettale nell'anziano.

The early rectal cancer which needs conservative surgical treatment should present some pathological characters: intramucosal site without muscularis invasion (pT1), high or moderate differentiated grading (GI-G2), no lymph node metastasis or vascular invasion. Total mesorectal excision is the gold standard for these neoplasms and permits very low resection or colo-anal anastomosis with sphincter function preserving. However, this type of surgery has still a high percentage of postoperative morbidity and mortality (some authors report respectively 40% and 5%). Therefore the local excision in selected cases is able to preserve the sphincter function and to reduce the postoperative complications with high probability of recovery.

[Intestinal infarction in the elderly]. / L'infarto intestinale nell'anziano.

The bowel infarction is till affected by high mortality in spite of new diagnostic methods and therapy. In our experience was observed about 45 patients with bowel infarction by different etiology; fast diagnosis and therapy are necessary for a good prognosis. The arteriography, at the light of this experience, is the gold standard but it is still performed in a low number of patients. The laparoscopy, in the advanced pathologies, is able to avoid an ineffectual laparotomy and permits a better diagnosis in borderline cases.

[Therapeutic strategy in neoplasia of the pancreas and ampulla]. / Strategie terapeutiche nelle neoplasie del pancreas e dell'ampolla.

The major symptoms of periampullary neoplasia are jaundice, lowering of weight, abdominal pain extending behind; diabetes, pancreatitis or exocrine pancreatic failure are uncommon. In the last years, surgery has been considered as the gold standard of the therapy because new technologies are able to reduce morbility and mortality. In the too advanced neoplasia, palliative surgical care permits better survival and quality of life. The duodenopancreatectomy today has a low perioperative mortality (0-3%) and an acceptable survival (15.25%). Good results were found for palliative surgery in unresectable neoplasms while in the inoperable patients we consider endoscopic and radiological treatments better than chemotherapy because they are able to correct the jaundice, improving quality of life (but not survival).

[The palliative treatment of hepatocarcinoma: chemoembolization vs. the combination of tamoxifen plus beta-interferon]. / Il trattamento palliativo dell'epatocarcinoma: la chemoembolizzazione vs l'associazione tamoxifene più beta-interferon.

Clinical and experimental data show that beta-IFN enhances the effect of tamoxifen on advanced breast cancer. There is a similarity between breast and liver as far as the proliferating effect on normal and neoplastic tissue of estrogen and progestin receptors is concerned. The authors tested this pharmacological association in unresectable liver neoplasms. They considered 76 (not randomized) patients affected with HCC; 38 were treated by trans-arterial chemoembolization (TACE) and 38 to beta-INF and tamoxifen (the 2 groups were comparable according to age, sex, Child-Pugh score, Okuda and TNM stages, cirrhosis etiology). The treatment response (positive when a tumor diameter decreased or stabilization was observed) was similar in the two groups; in the TACE group, the presence of a peritumoral capsula had a significant influence on survival (p < 0.02); on the other hand, in the patients treated with beta-INF and tamoxifen important factors for a better prognosis were the TNM stage (I and II, p < 0.02) and a symptom-free condition (p < 0.04). The authors believe the beta-INF and tamoxifen treatment could represent an effective alternative in the management of unresectable HCC. A better knowledge of the presence and meaning of estrogen and progestin receptors in the neoplastic tissue may allow a better selection of patients.