Sir: The authors treated 20 patients (13 women and seven men, aged between 35 and 75 years) affected by chronic venous insufficiency (i.e., the cause of ulcerations in 60 to 80 percent of patients with chronic leg ulcers) and diabetic foot ulcers with platelet gel mixed with fat tissue centrifuged at the Department of Plastic and Reconstructive Surgery of the “Tor Vergata” University of Rome. On a microscopic level, lymphatic vessels were enlarged and capillaries were elongated and dilated, with the functional number of capillaries being reduced.1 These microscopic changes resulted in the reduction and stagnation of blood flow and decreased oxygen levels at the capillary level in the preulcer skin, and increased flow and arteriovenous shunting in nearby tissues.2 The preoperative study was carried out by means of a complete clinical examination, a photographic examination, and through RM of the tissue. Postoperative follow-up took place after 2 and 5 weeks; 3, 6, and 12 months; and then annually. Platelet gel is a mixture of autologous proteins and contains more than 300,000 to 350,000 platelets/μl, whose action consists of stimulating skin fibroblasts when injected at mixed depth (the authors use 0.5 ml of platelet gel mixed with 1 ml of centrifuged fat tissue) favoring tissue growth by new synthesis of collagen. The authors use a platelet-rich plasma product by Cascade System (Esforax, Rome, Italy). We harvested fat tissue in the abdominal region using some specific cannulas 1.5 mm in diameter. Maintaining asepsis, we took the plungers of syringes and closed them with their cap, and then we positioned them, flatly, in the sterile centrifuge (Coleman technique).3 Fat tissue (processed for 3 minutes at 3000 rpm) mixed with platelet gel is implanted at different levels in small tunnels created previously, forcing the cannula with precise, controlled movements. Small quantities of fat cells are laid, one or two at a time, in the exiting movement of the cannula to create a large grid to favor a correct vascular development around each fat cell.4 In contrast, the authors used conservative treatment that included elevation, local treatment (biosynthetic material), and vacuum therapy. Until recently, this was considered the mainstay of treatment, and its success in achieving ulcer healing has been documented. Ulcer recurrence has been a nagging problem when only conservative treatment has been used. Slow healing and the significant recurrence rate of ulcers given conservative treatment reflect the failure to treat the underlying causative venous hypertension.5 The authors observed that 16 of 20 chronic lower extremity ulcers reepithelialized during a 9.7-week (average) course of twice-daily wound treatment with platelet releasate suspended on a collagen base (platelet-derived wound-healing factor) compared with two of 10 similar wounds treated with placebo. After crossover of the placebo group, all 11 nonhealed wounds achieved 100 percent epithelialization in an average of 7.1 weeks. Collectively, they provide evidence for the clinical use of platelet technology in the healing of both soft- and hard-tissue wounds. The results we obtained prove the efficacy of combining these two treatments, and the satisfaction of the patient confirms the quality of our results. V. Cervelli, M.D. Pietro Gentile, M.D. C. U. Casciani, M.D. Department of Plastic and Reconstructive Surgery “Policlinico Casilino” University “Tor Vergata” Rome, Italy

It is a truism to state that in cancer the extent to which the disease has spread (stage) is probably the most important factor determining patient prognosis and must be given prime consideration in evaluating and comparing different therapeutic regimes. Because of this, clinical screening tests (such as a rectal exam proctoscopy and colonoscopy), if tissue that is not normal is found, should include analyses contributing to the patient disease stage classification. However, the difficulty involved in this, principally due to the absence of reliable early prognostic indices of the disease stage, makes the cancer patients' treatment full of problems and risks. By a retrospective statistical study on pre-surgery peripheral blood immunological parameters of our groups of colorectal cancer patients and healthy subjects, we evaluated our previously suggested possibility of defining stage prognostic indices by parameter blood range values, evaluating their ability in the stage classification compared to the pTNM method. We have investigated the serum levels of various cytokines and cytokine receptors, leukocyte surface markers, peripheral blood mononuclear cell (PBMC) cytokine production and PBMC proliferative response. Statistically significant correlations between a variety of these immunological parameters and the disease stage were found but as a clinical patient screening of all parameters is quite expensive, to identify, the greatest stage weighting parameter and the respective blood range values, we performed a multivariate statistical analysis. We found that the blood ranges of IL-4 serum level and the PBMC proliferative response to anti-CD3 monoclonal antibody (mCD3) stimulus may be reliable prognostic indices which may contribute to an early disease stage classification in colorectal cancer patients, since they seem to be valid as the pTNM method Moreover, as the immunological prognostic indices could be a useful tool to evaluate the patient immune response, they may also improve the definition of the patient's stage classification for the selection of treatment and restaging procedures for the evaluation of the treatment benefit and recurrent disease.

BACKGROUND:The authors report their experience with autologous graft rhinoplasties.METHODS:Data were collected retrospectively, with selection of only autologous grafts from 2,000 rhinoplasties performed at the Plastic and Reconstructive Department of the University of Rome Tor Vergata.RESULTS:A total of 62 patients from January 1995 to January 2005 were selected. Most of the patients were treated with the "open tip" technique, whereas 9.7% had a classic endonasal approach. Follow-up evaluation was performed with outpatient visits at 2 and 6 weeks, then at 3, 6, and 12 months. Good aesthetic results were obtained for 93.5% of the patients, and 83.7% had complete satisfaction.CONCLUSION:Autologuos cartilage graft rhinoplasty is an affordable technique easy to learn that widens possibilities of interventions for nasal pyramid reconstruction.

The authors present their experience with the correction of deformities of the nasal saddleback using rib cartilage grafts. They present a review of international literature on this topic, analyzing 33 patients selected from 452 cases of rhinoplasties performed between January 1990 and December 2004 at the Department of Plastic and Reconstructive Surgery of the University of Rome "Tor Vergata." Nasal saddleback is one of the most complicated defects to correct surgically. It can be a consequence of nasoethmoid-orbital fractures and is in this case associated with other evident signs like telecanthus, teleorbitism, or orbital dystopia. It can be also a consequence of surgical procedures in the nasal area where a loss of bone or septal cartilaginous support has occurred. They compare the techniques employed in the reconstruction and describe the advantage of the use of cartilage from the 11th rib and evaluate the results of an engineering analysis of tension forces on the rib cartilage. Of the total number of patients treated, good cosmetic results were obtained in 84% of the cases and excellent functional results in almost all of the cases (94%).

AIMS:All convective hemodiafiltration techniques require a replacement fluid, which must have an adequate electrolytic composition and must be sterile and pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be "regenerated" and used as a replacement fluid (hemo-filtrate reinfusion; HFR). The aim of this study was to evaluate whether the HFR technique as suggested in its original configuration could be improved by inverting the purification sequence (post-dilution HFR; PDHFR) in order to increase the purification efficiency of the whole system.METHODS:We performed standard HFR in 6 uremic patients during 6 months and, subsequently, during further 6 months, PDHFR. The dialytic efficacy of the two techniques and the filter blood loss were evaluated. Moreover, we studied how both techniques affected cytokine levels.RESULTS:We observed a significant increase of urea extraction and of Kt/V values in PDHFR. An equally significant improvement was observed in regard to the extraction of beta2-m and the blood loss. Furthermore, IL6 and TNFalpha decreased significantly after PDHFR treatment.CONCLUSIONS:HFR has proven to be an easy-to-perform hemodiafiltration technique, capable of resolving the typical problem of the other hemodiafiltration technique, the availability and production of a sterile and ultrapure reinfusion solution. The inversion of its configuration has allowed us to improve three aspects that have characterized, in our experience, the treatments performed in the original geometry: the removal of both urea and beta2-m, and the filter. Finally, it's notable that the decrease in cytokines levels achieved with PDHFR might attenuate the uremic micro-inflammatory state.

We describe an additional HLA-Cw*02 variant, HLA-Cw*0208, which has been identified in a renal transplant recipient of Caucasian origin (Italy). After performing preliminary serological typing, we analyzed exons 2 and 3 of the HLA-C locus polymorphism by cloning the amplified DNA and using a sequence-based typing method. The new allele differs from Cw*020202 by one nucleotide substitution at nucleotide 61 (G-->A) of exon 2, which translates to a difference of one amino acid at residue 21 (His-->Arg) of the HLA-C heavy chain. We propose that Cw*0208 was generated by a random point mutation in codon 21 from the Cw*020202 allele, or through gene conversion of Cw*020202 with another allele, probably the Cw*1205 and Cw*1602 alleles.

Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction.MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.

INTRODUCTION:Reactivation of polyoma virus BK (BKV) is increasingly recognized as a cause of severe renal-allograft dysfunction. The aim of the present study was to evaluate prevalence of BKV infection and activity in a population of kidney (KT) and liver (LT) transplant patients and search for a possible correlation with renal dysfunction.METHODS:We studied 118 patients for BKV viruria and, when present, for BKV viremia. We also assessed HCV status.RESULTS:Among 16 patients with BKV viruria (5 LT and 11 KT), eight showed BKV viremia (one LT and seven KT). Among BKV viruria-positive patients, three LT recipients were HCV-positive. All LT BKV viruria-positive patients showed normal renal function with a mean serum creatinine (sCr) blood level of 0.9 mg% and a mean blood urea nitrogen (BUN) value of about 36 mg%. The mean transplant age was 2.5 years. In contrast, KT BKV viruria-positive patients showed impaired renal function which was slightly worse in patients who also displayed BKV viremia, namely, a mean sCr blood level 1.7 mg% and a mean BUN value about 80 mg%. The mean transplant age was 7 years.CONCLUSION:Based on these findings, it seems that BKV viruria in renal allograft recipients may be associated with viremia and related to nephropathy that may lead to allograft rejection. The study will be completed with a 2-year follow-up of positive patients to assess the possible relationship between BKV active infection and eventual decrease of renal function and loss of transplanted organ.

OBJECTIVE:To evaluate whether a dietary protein restriction is useful for slowing the progression of chronic renal failure (CRF) in diabetic and nondiabetic patients and to analyze the possible risk of malnutrition after such a dietary regimen.DESIGN:Prospective, randomized case-control clinical trial.SETTING:Nephrology outpatients.PATIENTS AND OTHER PARTICIPANTS:A total of 169 patients, 89 affected with CRF and chronic hypertension and 80 affected with overt diabetic nephropathy (24 suffering from type 1 and 56 from type 2 diabetes) and chronic hypertension.INTERVENTION:Diabetic patients and nondiabetic patients were randomly divided into 2 groups: 40 diabetic patients received a low-protein diet (0.8 g/kg/day) and 40 were maintained on a free protein diet; similarly, 44 nondiabetic patients received a low-protein diet (0.6 g/kg/day) and 45 were maintained on a free protein diet. The investigation lasted 1 year.MAIN OUTCOME MEASURE:Renal function and nutritional status.RESULTS:At the end of the study, there were no statistically significant differences in renal function between treated and nontreated diabetic patients, whereas treated nondiabetic patients showed a lower decrease in renal function compared with the nontreated group. In both diabetic and nondiabetic patients, the mean body weight and obesity index decreased significantly in treated patients compared with nontreated ones. Serum albumin and prealbumin were stable in all patients during the whole study time, and there were no other signs of malnutrition.CONCLUSION:An adequate dietary protein restriction is accepted by patients, and it is well tolerated during a 12-month follow-up. Without any sign of malnutrition, it is possible to get near the ideal body weight and to reduce the obesity index and the body mass index, which are both well-established risk factors for developing cardiovascular pathology. In nondiabetic patients only, we observed a significant slowing of the progression of renal damage.

Portal vein thrombosis (PVT) is a frequent finding in liver transplantation, the management of which depends mainly on its extent. In cases of mild to moderate PVT, a low dissection of the portal trunk, a jump graft, or direct implantation of graft portal vein into large venous collaterals or thrombectomy offer alternatives. For severe PVT anecdotal reports suggest that cavoportal hemitransposition, portal arterialization, or combined liver and intestine transplantation may be attempted, although the results to date are not satisfactory. When extensive perivenous and venous inflammatory changes reach the infrapancreatic region, liver transplantation probably should not be performed due to the high mortality rate.

Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 μg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.

PURPOSE:Hemodiafiltration reinfusion (HFR) is characterized by the use of regenerated ultrafiltrate as replacement fluid. We devised a new technique, post-dilution HFR, aimed at increasing the purification efficiency, treatment tolerability and at reducing inflammatory state.METHODS:We performed post-dilution HFR in six uremic patients during 18 months. Dialytic efficacy, filter blood rest and cytokine behavior were evaluated.RESULTS:Neither pyrogenic reactions nor other adverse phenomena were recorded. The tolerance to the treatment was excellent. We observed a high rate of urea extraction and optimal Kt/V values, a high extraction of beta2 microglobulin (beta2-m) and a reduction in blood rest; in addition, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) significantly decreased. CONCLUSIONS. The inversion of the standard HFR configuration allowed us to improve the removal of both urea and beta2-m, and the blood rest, with an optimal tolerability. Moreover, the reduction in cytokine levels could attenuate the uremic microinflammatory state.

P545 Aims: Chronic renal failure (CRF) is a recognized complication of organ transplantation and several risk factors there exist, linked both to patients and the procedure, which can favor its development. The aim of this study was to assess the incidence of post-transplantation CRF in a population of liver transplanted patients and to investigate the presence of possible risk factors for developing renal dysfunction. Methods: We performed a retrospective study on the liver-transplanted patients referring to liver transplantation ambulatory of “Tor Vergata” University of Rome and investigated the incidence of CRF and eventual need for renal replacement therapy (RRT). Furthermore, we searched for some possible risk factors for CRF development, such as systemic hypertension (SH), dyslipidemia, Diabetes Mellitus (DM), HBV and HCV status and calcyneurin inhibitors therapy. Results: From 1992 to today, 261 ortotopic liver transplantation have been performed at our Centre. In the post-transplantation period, 22 patients (8,4 %) developed chronic renal failure and were treated with standard intermittent hemodialysis (for a men time of 3 weeks). Among these, four male patients and one female subject have developed end stage renal disease (ESRD) and at present need chronic RRT. Further data about ESRD patients are reported in the Table below. One of them has died for cardiovascular complications during dialytic session.FigureAmong the remaining 17 patients, 5 subjects (29,5%) were HCV positive, 9/17 (52,9%) showed SH, 2/17 (11,8%) showed DM and 10/17 (58,8%) were treated with CsA. They partially recovered their renal function and are at present under conservative therapy. Conclusions: CRF proved to be a relatively common complication in our liver transplanted patients, confirming data reported in literature. Risk factors for developing renal dysfunction present in our patients are also cardiovascular risk factors and this could lead to an increase in mortality for cardiovascular pathology, particularly incident in uremic patients. It could be useful to pay attention to pre-transplant renal dysfunction, modifiable cardiovascular risk factors and immunosuppressant protocol in order to avoid CRF onset in liver transplanted patients, thus obtaining a reduction of morbidity and mortality and of the costs for the National Sanitary System.

A 71-year-old-woman was admitted to the S. Eugenio Hospital for a history of progressively impaired standing and gait. Anamnesis revealed systemic hypertension, gastric polyposis and juvenile pulmonary tuberculosis. Neurological examination showed a severe truncal and gait ataxia, without any sensory-motor impairment. Motor and somato-sensory evoked potentials were normal. Brain Magnetic Resonance Imaging (MRI) showed minimal signs of chronic ischemia only at a supratentorial level. Cerebral Single Photon Emission Computed Tomography, spinal MRI, total body computed tomography, Esophagogastroduodenoscopy, and finally total body Positron Emission Tomography resulted negative for neoplasms. Oncological serum markers were negative. Serum antibody against Purkinje's cells (Anti-Yo) was detected and titer was 1 : 80, while normally it should be undetectable. Other autoantibodies (Anti-Hu, Anti-Ri) were undetectable. Two sessions of plasma exchange (PE) were thus performed, leading to a rapid, marked and durable improvement of standing and gait and to a reduction of the autoantibody, which became undetectable. No serious adverse effect was noted. Although no definite therapy for autommume cerebellar ataxia has been established, PE should be considered as one of the main therapeutic choices.

The authors describe the first human renal transplantation and the first renal xenotransplant in Italy and the atmosphere at the University of Rome where these transplants were performed. Just a few months after those events, a state law was approved which allowed kidney donation.

BACKGROUND:Haemorrhoid disease has become more and more frequent during the past years among western populations. Great attention has been paid in development of surgical procedures, in order to reduce post-operative pain (the main adverse effect of surgical treatment for haemorrhoids) and shorten execution time and hospital stay. This randomised clinical study compares the results obtained using submucosal haemorrhoidectomy with radiofrequency vs. diathermic haemorrhoidectomy.METHODS:Thirty-one patients were randomised to undergo submucosal haemorrhoidectomy with radiofrequency bistoury (16 patients, Group A) or diathermic haemorrhoidectomy (15 patients, Group B). The operating time, amount of pain and postoperative analgesic requirement, intra and post-operative complications and patient satisfaction were documented.RESULTS:The mean values for operative time have been 35.8 min for group A and 23.2 min for group B. According to pain score, patients' mean values for first day postoperative pain were 3.8 (A) and 5.8 (B). Pain at first evacuation 4.7 (A) and 6.5 (B). Pain at 7th postoperative day was 2.3 (A) and 3.7 (B). Patient's postoperative satisfaction rate was 6.0 (A) vs. 5.2 (B) at 3rd day and 6.7 (A) and 5.7 (B) at 6 months.CONCLUSIONS:In spite of relatively difficult execution and longer operating times, submucosal haemorrhoidectomy with radiofrequency bistoury appears to be the most precise and accurate treatment for IV degree haemorrhoids. Performing submucosal haemorrhoidectomy with radiofrequency bistoury allows us to reduce postoperative pain, bleeding and shorten hospital stay.