Gianfranco Ferla

Analysis of Prognostic Factors Influencing Long-term Survival After Hepatic Resection for Metastatic Colorectal Cancer

BackgroundThe aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases.MethodsThe variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS).ResultsThe univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS.ConclusionsNo single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3–G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.

Ultrasound Measurement of Visceral and Subcutaneous Fat in Morbidly Obese Patients Before and after Laparoscopic Adjustable Gastric Banding: Comparison with Computerized Tomography and with Anthropometric Measurements

Background: There are now a variety of methods to assess body fat distribution, anthropometric (waist circumference and waist/hip W/H ratio), computed tomography (CT), and ultrasound (US) measurements, with CT considered as the reference method. Bariatric surgery leads to a significant and usually durable weight loss in morbidly obese patients; when assessing its results, it is of interest to measure changes of total fat tissue and of body fat distribution. Methods: In this study, we compared anthropometric, US, and CT measurements of body fat distribution under basal conditions and 1 year after laparoscopic adjustable gastric banding (LAGB); 120 morbidly obese patients were considered at baseline, and 40 patients were re-evaluated 1 year after LAGB. Results: Thickness of visceral and subcutaneous fat measured through CT and US methods was superimposable both under basal conditions and 1 year after LAGB, and the highest correlation was found between CT and US data on visceral fat, followed by CT and US data on subcutaneous fat; a fair correlation was also found between CT and US data on visceral fat and waist circumference. Conclusion:We suggest that evaluation of body fat distribution is accomplished by US instead of CT measurement, because of its lower cost and low exposure risk. Waist circumference stands as a reasonable surrogate of both methods, while W/H ratio is poorly correlated with other measures of body fat distribution.

Magnetic Resonance (MR) Imaging and MR Spectroscopy of Nerve Regeneration and Target Muscle Energy Metabolism in a Model of Prosthesis-Guided Reinnervation in Rats

RATIONALE AND OBJECTIVES We monitored the regeneration of the rat sciatic nerve after its transection and the concomitant alteration in the high-energy phosphates content in the target tibialis anterior muscle. METHODS Rat sciatic nerve was resected and the gap connected with a prosthesis of polytetrafluoroethylene. Progress of reinnervation was monitored by 1H MR imaging, whereas muscular energy metabolism was evaluated by localized 31P MR spectroscopy. RESULTS Reconstitution between the nerve stumps was resumed 8-12 weeks postoperatively. The ratio of phosphocreatine to inorganic phosphate reached a plateau at 46% of the initial level approximately 8 weeks after the operation and recovered thereafter. Immediately after the surgery, muscular pH became slightly alkaline and returned to normal with the progress of reinnervation. CONCLUSION Recovery of the muscular energy metabolism began after the reconnection of the severed nerve stumps. The combination of MR imaging and MR spectroscopy followed noninvasively the progress of reinnervation and muscular energy metabolism of the prosthesis-guided nerve regeneration.

Morphological and Functional Evaluation of Peripheral Nerve Regeneration in the Rat Using an Expanded Polytetrafluoroethylene (PTFE) Microprosthesis

The aim of our study was to evaluate in the rat the ability of a polytetrafluoroethylene microprosthesis (PTFE), to guide the peripheral nerve regeneration between the two extremities of a transected sciatic nerve. In 15 adult male Wistar rats, weighing 200 g, a segment of the right sciatic nerve was resected, leaving a gap of about 1 cm, bridged with microprosthesis, using our original microsurgical technique. Neurophysiological evaluations were performed at 6 and 9 months post-operatively to study the distal motor latency either in the right sciatic nerve or in the unoperated control side. In all the rats myoelectrical responses with an increased latency of the operated side were produced from the interosseous muscle of the foot. The animals were sacrificed 9 months post surgery. Histological sections at the level of the graft were done in all the rats, and in 10 animals biopsies of the tibialis anterior muscle (TA) of each side were performed. An active process of axonal regeneration was documented inside the graft, with no infiltration of nerve fibers through the wall of the prosthesis. A connective fibrous reaction was present around the external wall of the graft. Muscle biopsies showed definite signs of muscle reinnervation, with residual features of variable degree of denervation. These findings stress and confirm the ability of the PTFE graft to allow effective regeneration in a peripheral nerve gap in the rat.

Xenotransplantation Rejection is Antibody-Mediated in Both Sensitized and Nonsensitized Recipients

This study analyzes the mechanisms involved in xenotransplantation rejection between closely related species. Hamster hearts were transplanted heterotopically into both normal rats and rats previously sensitized by the transfusion of donor blood. Sequential ultrastructural and immunohistochemical analyses were performed on the grafts, spleens, and sera. The data obtained support the view that induced antibodies directed against the xenograft endothelium play a very important role in producing graft damage. Moreover, the demonstration of antibodies against myocyte determinants suggests that it is possible, in this particular model, that the antiendothelial antibodies are not the only ones involved in the injury process.

Intestinal Microflora Settlement in Patients with Jejunoileal Bypass for Morbid Obesity

Intestinal microflora settlement was evaluated in this retrospective study of 49 patients with jejunoileal bypass who required reoperation. Colonic microflora was observed in the samples of the contents of the functioning jejunum and ileum but not in 55% of the samples from the middle of the excluded loop. Colonization of the excluded loop was not detected in patients without clinical signs of bacterial overgrowth but was significantly frequent (p < 0.01) in those with clinical signs (bloating, migratory arthralgias, rashes, skin lesions). However, positive excluded loop cultures were not always associated with clinical manifestations. No significant correlation was observed between bacteriology of the contents of the excluded loop and bypass results. The success of an intestinal bypass may depend not only on anatomic and functional adaptation to the new, surgically created conditions, but also to the attainment of microbiological equilibrium in the intestinal ecosystem.

Surgical approach to multifocal hepatocellular carcinoma with portal vein thrombosis and arterioportal shunt leading to portal hypertension and bleeding: a case report.

It is reported the case of a 69 years man who presented to the Emergency Room because of pain and abdominal distension from ascites. After admission and paracentesis placement, he developed a digestive hemorrhage due to oesophageal varices from portal ipertension secondary to the formation of a portal shunt concomitant with a multifocal HepatoCellular Carcinoma (HCC) with portal vein thrombosis (PVT). The patient underwent endoscopic varices ligation, twice transarterial embolization (TAE) of arterial branches feeding the shunt and subsequent left hepatectomy. During the postoperative course he developed mild and transient signs of liver failure and was discharged in postoperative day 16. He is alive and disease free 8 months after surgery.

Antibody binding to endothelial and epithelial antigens triggers pig-to-rabbit xenograft rejection and its absence results in atypical complement deposition

In pig-to-rabbit kidney xenograft (PRKX), endothelial antigen determinants (EAD) are immediately recognized by IgG and IgA, while IgM does not react with them. The purpose of this study was to investigate the different roles of IgG, IgA, IgM, and complement in the hyperacute rejection of a PRKX model. Nine isolated Landrace pig kidneys were each perfused with 10 ml normal New Zealand rabbit serum. Perfusates (serum A) were collected after discarding the first 0.5 ml. Serum A and rabbit complement were then incubated for 30 min with frozen sections of normal pig kidney. After washing with buffer solution all the specimens were treated for immunohistochemistry. Three frozen sections of normal Landrace pig kidney and three samples of normal New Zealand rabbit serum were used as controls. Immunohistochemical analysis of the nine perfused kidneys demonstrated IgG, IgA and C3 deposition on the peritubular and glomerular vascular endothelium. No IgM reactivity was shown. In the frozen sections exposed to serum A, immunofluorescence showed minimal IgG, IgA and C3 reactivity while IgM deposition was clearly evident on the tubular epithelium. Immunofluorescence of frozen sections exposed to rabbit complement, done by fluorescein-labeled goat anti-rabbit C3 antibodies were positive only in the glomerular endothelium. The same rabbit complement was active in antibody dependent cytotoxicity on human T cells. Our results indicated that in the PRKX model, IgG and IgA acted as preformed antibodies recognizing endothelial EAD. IgM did not bind to any endothelial molecules, but recognized antigens located on the brush border of the tubular epithelium. Furthermore, in this model, absence of antigen-antibody complexes resulted in atypical complement deposition.

Criteria for choosing the most adequate access for long-term central venous catheters.

During the last two decades the increasing use of new drugs and drug schedules in cancer therapy has led to the frequent need for prolonged central venous catheterization. Furthermore, progressive loss of peripheral venous accesses is a common problem in cancer patients, providing significant distress to frequently already compromised patients and jeopardizing the results of chemotherapy due to incomplete or delayed drug administration. Finally, long-term central venous access is often required for the administration of parenteral nutrition, analgesics, blood products, etc. to provide the best supportive care to the patient. For these reasons surgeons working in cancer institutes often have to implant long-term central venous access devices at the time of the first treatment of the patient (eg, when giving neoadjuvant chemotherapy for lung or rectal cancer), after surgical procedures (adjuvant chemotherapy after radical surgery) or when chemotherapy is the only treatment planned (metastatic cancer, lymphoproliferative diseases, etc.). Since several central veins and techniques are available for long-term cannulation, the best choice with respect to the treatment and the patient has to be carefully evaluated and can no longer be determined on a personal preference or, worse still, a random basis. The choice of the best long-term venous access should depend on three factors: the type of procedure, the vein, and the patient. Only if the procedure is planned after a complete evaluation of the combination of these three factors can the best results be obtained.