Protective effect of an inhibitor of interleukin-8 (meraxin) from ischemia and reperfusion injury in a rat model of kidney transplantation.

INTRODUCTION: Since the ischemia and reperfusion injury is one of the main causes of delayed graft function after transplantation, research efforts have focused on studying the molecules involved in this inflammatory process. The chemokine interleukin-8 (IL-8) seems to be the main one responsible through a chemoattractive action toward neutropils. Therefore, one of the strategies adopted to prevent this process is blocking the binding between IL-8 and its receptors. The aim of our study was to test the effect of meraxin, a new derivative from repertaxin, to protect the renal graft from ischemia and reperfusion injury. MATERIALS AND METHODS: Eighty male syngenic rats were divided into four groups. The control group underwent only kidney transplantation, while the other groups were treated with meraxin at various dosages 2 hours before graft reperfusion. Blood and histological samples were taken at sacrifice 24 hours after transplantation. RESULTS: Creatinine was significantly lower in the group treated with the high dosage of meraxin. Histological observation of the grafted tissue showed instead only a mild and not significant neutrophilic infiltration, equal in each group. CONCLUSIONS: Graft function was improved by the administration of meraxin at high dosage, but this effect did not seem to be connected to a reduction in inflammatory infiltration in the parechymal tissue. Maybe the cause is in the mechanisms of clotting activation, due to alteration of adhesion molecules and endothelial cells.

Bologna transplant center results in double kidney transplantation: update.

INTRODUCTION: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of this study was to verify the results obtained with double-kidney transplantation in terms of graft/patient survivals and complications. PATIENTS AND METHODS: Between September 2001 and September 2006. 26 double-kidney transplantations were performed in our center. Indications for surgery were: chronic glomerulonephritis (n = 17), polycystic disease (n = 4), reflux nephropathy (n = 1), hypertensive nephroangiosclerosis (n = 4). The kidneys were all perfused with Celsior solution and mean cold ischemia time was 16.7 +/- 2.5 hours. In all cases, a pretransplant kidney biopsy was performed to evaluate the damage (mean score: 4.3). Immunosuppression was tacrolimus-based for all patients. RESULTS: Eighteen patients had good renal postoperative function, while the other eight displayed acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31%. There were two surgical reoperations for intestinal perforation. Graft and recipient survivals were 82.7% and 100%, and 78.9% and 94% at 3 and 36 months, respectively. CONCLUSIONS: Double-kidney transplantation is a safe strategy to face the organ shortage. The score used in this study is useful to determine whether a kidney should be refused or suitable for single- or dual-kidney transplantation. The results of our experience are encouraging, but the series is too small to allow a conclusion.

Portal vein arterialization in hepatobiliary surgery and liver transplantation.

We reviewed the literature reports and our personal experience on partial portal vein arterialization (PPVA) to prevent and treat acute liver failure (ALF) following major hepatobiliary surgery or another etiology. Experimental studies in rats have assessed the efficacy of PPVA in treatment of ALF induced by extended resections in normal or fatty livers or in toxic carbon-tetrachloride damage. The treated groups showed greater survival and faster recovery of liver function. Among 11 clinical cases reported in the literature, PPVA was performed in four cases to prevent and in seven cases to treat ALF. Eight patients survived, showing rapid recovery of liver function and resolution of the clinical condition. This relatively simple procedure has shown itself able to promote liver regeneration. The PPVA procedure has shown itself to be safe and simple as well as to offer a promising approach to the failing liver.

[The surgical treatment of the diastasis recti abdominis: an original technique of prosthesis repair of the abdominal wall]. / Il trattamento chirurgico degli sventramenti spontanei: tecnica originale di protesizzazione della parete addominale.

The Authors talk about on the surgical correction of the diastasis recti abdominis and underline its indications and aims. Firstly, they specify the possibilities and define the limits of the traditional surgical method. Secondly, they illustrate the rational of an innovating and original technique of prosthesis repair of the abdominal anterior wall setted up to treat the important diastasis recti abdominis. Particularly, this technique is the result of a kind of eclecticism and integration of some phases of the Quénu's self-plastic surgery and of the Welti-Eudel and Chevrel's technique. Thirdly, the authors describe the sequence of the times of the new technique and present the preliminary clinical experience carried out with it. Therefore, they determine gratifying and encouraging the findings of this method as regards the immediate and enduring curative efficacy (cosmetic and functional), the security and the compliance of the patient. Finally, in accordance with the outcomes, the authors decide to defend the undoubted reliability of the prosthesis repair of the abdominal wall to treat the big diastasis recti abdominis. Moreover, they intend to pass definitive judgement on the method after further clinical experiences on larger series of cases.

[The employment of an original ring handle forceps in anterior repair of the primitive inguinal hernia]. / L'impiego di un'originale pinza nella chirurgia per via anteriore dell'ernia inguinale primitiva.

The Authors propose the employment of an original dissecting and ribbon-carrier bevelled ring handle forceps in inguinal prosthetic tension-free hernioplasty with mini-inguinotomy. The surgical instrument, of stainless steel and 16 centimetres long, consists of two jaws with ring handle, ratchets and box lock nearly identical to those of common surgical instruments; is slightly curved in his distant part, where shows a large bevelled end and a large seizing, entirely original. The peculiar surgical instrument gives possibility to operator to make easily and delicately the atraumatic mobilization in proximity to the pubic tubercle of the spermatic cord from the back wall of the inguinal passage, in place of the index finger hook-shaped who, used roughly and by pulling in large incisions, cannot be used instead in the mini-incisions because of limited available space in the surgical site. On end, the new ring handle forceps allows to keep in suspension the spermatic cord by rubber ribbon more simply and rapidly than the usual big ligature-carrier. On the whole, the dissecting and ribbon-carrier bevelled ring handle forceps, whose the Authors use habitually the prototype in inguinal prosthetic tension-free hernioplasty with mini-inguinotomy, allows the execution of easy, prudent, elegant, precise, effective and above all safe surgical gestures.

An experimental pilot study on controlled portal vein arterialization with an extracorporeal device in the swine model of partial liver resection and ischemia.

AIM: To determine whether the physiologically oxygenated arterial blood reversed in the portal system by means of portal vein arterialization (PVA) through an extracorporeal device which we have called L.E.O2.NARDO (Liver Extracorporeal Oxygen. NARDO) is effective in treating swine with subtotal hepatectomy leading to acute liver failure (ALF). METHODS: Ten swine with ALF induced by 85-90% liver resection and five minutes of ischemia-reperfusion injury were randomly divided into two groups: five animals received PVA extracorporeal treatment and five swine were not-treated (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system. An extracorporeal device was interposed between the outflow and the inflow in order to monitoring the hemodynamic parameters. Each treatment lasted 6 hours. Serum and liver samples were collected in both groups. The survival was assessed at 1 week. RESULTS: The PVA-extracorporeal treatment yielded beneficial effects for subtotal hepatectomy-induced ALF swine with decreased serum ammonia, transaminases and total bilirubin as compared with the untreated group. INR recovered rapidly in the PVA-extracorporeal group remaining significantly lower than in untreated animals. The 7-day survival of PVA-extracorporeal group swine was significantly higher than that of untreated animals, with a statistically significant difference (p<0.05). Four swine in the PVA-extracorporeal group survived at 1 week while none of the swine in the control group were alive at that time; an average time of 144h+/-13h and 24.4h+/-5h was observed in the PVA-extracorporeal and control groups, respectively. CONCLUSIONS: Arterial blood supply in the portal system through the extracorporeal device is easily applicable, efficacious, safe and may represent a novel approach for ALF swine induced by subtotal liver resection.

The first case of ureteral duplication in a combined liver-kidney transplantation.

AIM: Kidney transplantation with ureteral duplication may represent a doubled risk factor in terms of ureteral stenosis or necrosis with urinary leakage usually from the site of ureteroneocystostomy. The incidence of complete duplication is very low at 0.19%. We report a kidney with ureteral duplication in the specific setting of multiorgan transplantation since it could be considered an adjunctive risk factor for urological complications. METHODS: The recipient was a 67-year old man, suffering from terminal renal insufficiency. He was also affected by HCV-related cirrhosis. The patient had been waiting for the combined transplantation for 27 months and in the last two months his hepatic function dramatically worsened. The donor was a 53-year old man who died of non-traumatic subarachnoid hemorrhage. Good HLA compatibility was observed between donor and recipient. During harvest both kidneys presented a complete ureteral duplication. So the ureters were freed together with a wide cuff of periureteral tissue and dissected distally. No vascular abnormalities were noted during the removal of either kidney. The grafts were flushed with University of Wisconsin solution and stored in the same solution. RESULTS: The liver was reperfused after 9 hours of cold ischemia. Subsequently the kidney was vascularized after 15 hours of cold ischemia. Urine production occurred immediately after revascularization. Two separated ureteroneocystostomies with a single antireflux technique were performed. Cyclosporine and steroids were given. Post-operative course was uneventful and liver and kidney function were normal. The 7-day cystography was normal. The 6, 12, 24 month ultrasonographies showed no signs of hydronephrosis or hydroureter. After 28 months renal cancer was diagnosed and the patient underwent a right nephrectomy. The liver-kidney recipient had excellent hepatic and renal function for 84.7 months. He died of malignancy from de novo tumor. CONCLUSIONS: On the basis of this experience, a kidney with an ureteral duplication, while rare, can be satisfactorily used also in combined liver-kidney transplantation.

Double kidney transplantation: initial experience of the Bologna Transplant Center.

AIM: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of the study is to verify the results obtained with double-kidney transplantation in terms of graft and patient survival and complications. METHODS: Between September 2001 and September 2004, 16 double-kidney transplantations were performed in our center. The kidneys were all perfused with Celsior solution and the mean cold ischemia time was 17.6+/-2.7 hours. In all cases a pre-transplant kidney biopsy was performed to evaluate the damage. Immunosuppression was tacrolimus based for all patients. RESULTS: Eight patients had good renal postoperative function while the other eight had acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31.2%; there were two surgical revisions for intestinal perforation. The graft and recipient survival was 78.1% and 100% and 78.1% and 93.7% at 3 and 36 months. CONCLUSIONS: Double-kidney transplantation is a safe way to face the organ shortage. Moreover the score used in this study is useful to determine whether a kidney should be refused or suitable for single or dual-kidney transplantation. The results of our initial experience are encouraging, but this series is too small in number to consent a conclusive statement.

Portal vein arterialization for the treatment of post resection acute liver failure in the rat.

INTRODUCTION: Hyperoxygenation of the liver has been suggested to improve its regenerative capacity. Thus, this study sought to determine whether an additional supply of oxygenated blood delivered by portal vein arterialization (PVA) was protective against acute liver failure induced by hepatectomy. METHODS: Sprague-Dawley rats (six per each group) were divided to either undergo PVA or be untreated after extended hepatectomy. Liver injury was evaluated by the serum alanine aminotransferase (ALT) levels. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. Serum ALT levels were significantly reduced in arterialized versus nonarterialized rats. PVA promotes liver regeneration. Finally, PVA significantly improved host survival compared to the controls: 90% versus 30%, respectively. CONCLUSION: These data suggested that an additional supply of arterial oxygenated blood through PVA promoted a rapid regeneration, leading to a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool to optimize hepatocyte regeneration.

Successful treatment of CCL4-induced acute liver failure with portal vein arterialization in the rat.

INTRODUCTION: Optimization of the conditions for regeneration of the native diseased liver is a major goal in patients with acute liver failure. This study sought to determine whether portal vein arterialization (PVA), which increases the oxygen supply to the liver, was protective in a rat model of liver failure. METHODS: At 24 hours after CCl(4) intoxication, Sprague-Dawley rats (six per group) were assigned to receive PVA or as controls. We determined blood tests, histology, and 10-day survivals. Hepatocyte regeneration was assessed by the mitotic index and bromodeoxyuridine (BrdU) incorporation. RESULTS: Serum transaminases were significantly lower in PVA-treated rats than in control animals: liver necrosis resolved rapidly after PVA. The BrdU staining and mitotic index were severalfold higher among PVA-treated than in untreated rats. Survival was 100% among rats with PVA and 40% in untreated animals (P < .01). CONCLUSIONS: PVA led to resolution of CCl(4)-induced massive liver necrosis in the rat. This effect was probably mediated by activation of rapid and extensive hepatocyte regeneration. PVA might provide a novel, alternative approach to treat acute liver failure.

Portal vein oxygen supply through a liver extracorporeal device to treat acute liver failure in Swine induced by subtotal hepatectomy: preliminary data.

AIM: To determine whether the increase of oxygen supply in the portal system by a liver extracorporeal (L.E.O.NARDO) device is effective in treating swine with subtotal hepatectomy leading to acute liver failure (ALF). METHODS: Eight swine with ALF induced by 85% to 90% liver resection and 5 minutes of ischemia-reperfusion injury were randomly divided into two groups: four animals received L.E.O.NARDO treatment and four swine were not treated (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system. An extracorporeal device was interposed between the outflow and the inflow in order to monitor the hemodynamic parameters. Each treatment lasted 6 hours. Serum and liver samples were collected in both groups. The survival was assessed at 1 week. RESULTS: L.E.O.NARDO treatment yielded beneficial effects for subtotal hepatectomy-induced ALF in swine with decreased serum transaminases as compared with the untreated group. International normalized ratio recovered rapidly in the L.E.O.NARDO group, remaining significantly lower than in untreated animals. The 7-day survival of L.E.O.NARDO group swine was significantly higher than that of untreated animals, with a significant difference. Three swine in the L.E.O.NARDO group survived 1 week while none of the swine in the control group were alive at that time. CONCLUSIONS: Oxygen supply in the portal vein through the L.E.O.NARDO device is easily applicable, efficacious, and safe and may represent a novel approach for ALF in swine induced by subtotal liver resection.

Technical aspects of portal vein arterialization for acute liver failure: from rat lab to man.

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.

Kidney transplantation from elderly donors: a prospective randomized study comparing celsior and UW solutions.

AIM: The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. RESULTS: The warm ischemia time was 42.4 +/- 11 minutes among Celsior vs 46.9 +/- 17.9 minutes in the UW cohort (P = NS). The cold ischemia time was 18 +/- 4.5 hours in Celsior and 19 +/- 6.5 hours in UW (P = NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P = NS). Mean serum creatinine levels and mean daily urinary output were also similar. One- and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.

Portal vein arterialization: a new surgical option against acute liver failure?

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself, avoiding transplantation, is a major goal in the treatment of ALF. We report our clinical experience of portal vein arterialization in one case of massive liver necrosis after liver transplantation and in two patients with ALF caused by idiosyncratic drug reaction and mushroom intoxication. Portal vein arterialization, at least in two cases, was a turning point in the course of the disease since a close temporal association between surgery and clinical improvement was clearly evident. We believe that this novel approach, which should promote liver regeneration by providing an additional oxygen supply to the liver, may disclose a new possibility in the treatment of ALF and prompt new clinical and experimental research.

Preliminary results of a clinical randomized study comparing Celsior and HTK solutions in liver preservation for transplantation.

INTRODUCTION: A prospective, randomized, multicenter, open clinical trial was performed to compare the main liver function tests, postoperative complications, and early graft and patient survival of recipients transplanted with livers preserved in Celsior (CEL) versus histidine tryptophan ketoglutarate (HTK) solutions. METHODS: We analyzed the data from a single center. Forty livers randomized to CEL (n = 20) or HTK (n = 20) preservation solution were perfused in situ via the aorta and portal vein (CEL, 30 mL/kg via portal vein and 60 mL/kg via aorta; and HTK solution, 30 mL/kg via portal vein and 120 mL/kg via aorta). RESULTS: The groups were comparable with regard to donor, graft, and recipient characteristics. The mean cold ischemia time was 458 minutes (range: 203-667 minutes) in CEL and 450 (range: 310-684 minutes) in HTK. The incidence of initial poor function and primary nonfunction in CEL and HTK were (0 vs 1) and (0 vs 1), respectively. No differences were observed for acute rejection. No vascular or biliary complications were reported in either group. The 3-month graft and patient survival rates were 95% and 95% in CEL and 80% and 90% in HTK. The 12-month graft and patient survival rates were 90% and 90% in CEL and 75% and 85% in HTK. CONCLUSIONS: To our knowledge, this is the first report comparing CEL and HTK preservation solutions in clinical liver preservation. Although a greater 1-year graft and patient survival was observed in the CEL group, a definitive evaluation comparing CEL and HTK solutions in clinical preservation must await completion of the trial.

Octogenarian livers successfully transplanted in patients with fulminant hepatic failure.

Although octogenarian livers have been transplanted successfully in elective settings, their safety in the case of fulminant hepatic failure has not yet been reported. From November 1998 to June 2003, we transplanted 3 livers from 80-, 82-, and 86-year-old donors. The donors were hemodynamically stable with an intensive care unit stay ranging from 24-48 hours. Cold ischemia time was from 260 minutes to 526 minutes. Mild macrosteatosis was present in 2 donors. Donor and recipient characteristics as well as posttransplantation evolution were evaluated. Two cases had uneventful courses and all recipients are well at 39, 21, and 5 months, respectively. The second recipient underwent retransplantation at 15 days due to technical complications. Livers from octogenarian donors may be safely used in an emergency to save patients. Age does not represent a limit for individually assessed and highly selected donors.

Red blood cell transfusion in liver transplantation: a case-control study.

INTRODUCTION: We aimed to analyze the influence of intraoperative blood transfusion on postoperative complications and survival and to identify the preoperative variables associated with greater intraoperative bleeding. MATERIALS AND METHODS: Thirty-one elective liver transplantations (OLT) without blood transfusion performed between 1986 and 2002 (group 1) were compared with 62 patients (group 2) who underwent elective OLT with intraoperative transfusion after matching for gender, disease severity, and chronology. RESULTS: The hemoglobin and hematocrit values were significantly greater in group 1 compared to group 2. No significant differences were reported for the other parameters. In particular, the type of surgical technique had no influence on the blood requirement. As expected the nontransfused patients received less autologous packed red blood cells compared with the transfused patients. No differences were observed in either group for mean CIT, ICU and hospital stay, or acute rejection. A significant difference was observed in the number of postoperative infectious episodes, which was higher in group 2 (28 vs 5, P = .01). Graft and patient survivals at 3 months and 5 years did not differ significantly between groups. CONCLUSIONS: OLT without blood transfusion may be achieved in the presence of good recipient conditions. Lower preoperative hemoglobin and hematocrit values were associated with greater intraoperative transfusions.

[Angiodysplasia in the gastrointestinal haemorrhage of the elderly patient. Our experience]. / Le angiodisplasie nelle emorragie digestive del paziente anziano. La nostra esperienza.

Angiodysplasia of the digestive tract is one of the main causes of acute bleeding and is a frequent reason for admittance to the emergency surgery unit. This pathology, previously considered rare and often not recognised, has only recently acquired a precise anatomo-pathology thanks to endoscopy. Besides having a decisive diagnostic role, endoscopy also allows the control and successful treatment of lesions, often in a definitive way, which were previously only dealt with surgery, with significant advantages for the elderly patient, reducing the rate of morbidity and mortality. There are still many discussions today, above all on the priority of various diagnostic investigations to be carried out in digestive bleeding and on the choice of treatment in the case of angiodysplasic lesions in geriatric age. Some cases of acute bleeding from intestinal angiodysplasia, observed by the Authors, have led them to study the etiopathogenesis, diagnosis and emergency treatment of such lesions.

Incidence, predisposing factors, and results of surgical treatment of incisional hernia after orthotopic liver transplantation.

The literature provides little data about incisional herniae (IH) developing after orthotopic liver transplantation (OLTx). We evaluated the incidence, predisposing factors, and results of surgical treatment of this pathological condition. We reviewed the records of 718 consecutive OLTx performed in 623 patients between April 1986 and May 2002. Patients whose IH developed after transplantation were included in the study. We identified 31 patients (incidence, 4.9%) whose IH developed from 2 to 140 months after the transplantation. This complication was significantly more frequent in men. Important predisposing factors included: virus-correlated cirrhosis, body mass index >25, severe ascites, incision type for OLTx (bilateral subcostal extended upper midline to xiphoid), and post-OLTx complications. In 17 patients, repair of hernia was performed using direct fascial approximation, in 20 patients, it required a prosthesis. After hernia treatment, we observed no deaths but a morbidity rate of 6.4%, a mean postoperative hospital stay of 8 days and a recurrence rate of 6.4%. IH post-OLTx need surgical treatment.

Pyoderma gangrenosum of the "sinus mammarum" in ulcerative colitis.

The first part of this article deals with the report of a patient suffering from pyoderma gangrenosum of the "sinus mammarum" associated with asymptomatic ulcerative colitis. This is followed by a revision of the present epidemiological, etiological, pathogenetic and clinical knowledges about this systemic manifestation of chronic phlogosis of the colon. The Authors have analysed the treatment for this condition and emphasized the resistance of the cutaneous ulcer encountered to conventional medical therapy of the underlying colonic disease which proved to be efficacious only on the latter; this led to integrate traditional treatment with the use of perilesional injections of small doses of calcic heparin as an alternative to immunosuppressive drugs or surgery. Topical antithrombotic treatment, which can be justified by the histological findings of phenomena of the vasculitis in the edge of pyoderma gangrenosum, demonstrated to be crucial and represents a peculiarity in the case here reported, which is unique in the literature as far as the Authors know, since it has not been experimented by anyone else.