Biomedical subjects

G L Grazi

Publications and source records attributed to G L Grazi.

At least 19 recordsLinked to original sources

PubMed2006

Successful treatment of rhinomaxillary form of mucormycosis infection after liver transplantation: a case report.

Mucormycosis is a rare opportunistic infection, usually associated with immunocompromised states. Several conditions such as hematologic malignancy (leukemia, lymphoma, myeloma), solid organ transplantation, diabetes mellitus, corticosteroid therapy, or chemotherapy predispose patients to infection. The aim of this study was to present a single case of mucor infection after 900 consecutive liver transplantations. Rhinomaxillary mucormycosis must be suspected in a transplant recipient showing fever, maxillary swelling, and edema. This condition can be successfully treated with early diagnosis and a combination of aggressive surgery and antifungal therapy.

Antifungal Agents↗

PubMed2006

Posttransplant lymphoproliferative disorders in liver transplanted patients: a report of four cases.

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) are an uncommon but important cause of morbidity and mortality in solid organ transplant recipients. They are often the result of Epstein-Barr virus (EBV)-induced proliferation of B-lymphocytes in the setting of immunosuppression. PATIENTS AND METHODS: We retrospectively analyzed four cases of PTLD after liver transplantation. In all patients immunosuppression was reduced and anti-CD20 monoclonal antibody (rituximab) was administered. In two of four patients, EBV viral load was positive in the peripheral blood, and gancyclovir was therefore also prescribed. Chemotherapy (CHOP) was used as a rescue in the event of treatment failure. RESULTS: Even if no severe adverse events were observed during the treatment period, our treatment approach to PTLD was not effective, and only one patient out of four is still alive. CONCLUSIONS: Well-designed clinical trials are necessary to evaluate the role of this combined approach in the treatment of PTLD in liver transplant recipients.

Aged↗

PubMed2006

Surgical approach to complicated intestinal failure for benign disease in adult patients: transplantation or surgical rehabilitation?

Surgical approaches to complicated benign intestinal failure are gaining acceptance, especially in the pediatric population. Less international experience has been obtained in adult patients, who are usually treated with total parenteral nutrition (TPN). An intestinal rehabilitation program was started in our institution with comprehensive medical rehabilitation, surgical bowel rescue, and transplantation. Among 38 adult patients referred by our gastroenterologists for bowel rehabilitation and surgically treated in our institution, 92.2% received TPN on admission. After careful evaluation, 71% underwent transplantation. Five patients died, but 18 recipients were completely weaned off TPN at follow-up. Eleven patients underwent surgical resection of the affected bowel and a subsequent program of intestinal rehabilitation: they were all alive and weaned off TPN at discharge. At a 2-year mean follow-up, deaths occurred only in the transplant population. Therefore, intestinal surgical rescue, if successful, is optimal in adult patients.

Adolescent↗

PubMed2006

Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine.

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.

Adult↗

PubMed2006

Recovery from liver dysfunction after adult isolated intestinal transplantation without liver grafting.

PURPOSE: We sought to evaluate liver function recovery after isolated intestinal transplantation in adults with irreversible intestinal failure. PATIENTS AND METHODS: Over a 5-year period, we transplanted 34 adult patients, 25 of whom received an isolated intestinal graft, 4 a multivisceral graft without a liver, and 5, a multivisceral graft with a liver. Among the group of patients transplanted with the isolated graft we selected 14 recipients with pretransplant liver dysfunction, namely, a serum bilirubin >2 mg/dL (normal value: 1.2) and/or transaminases >100 IU/mL (NV, 37/40). Other inclusion criteria were total parenteral nutrition, period > 3 months, no diagnosis of portal hypertension or cirrhosis. Two patients had biopsy-proven liver fibrosis. RESULTS: At discharge, all patients recovered liver function to normal values: mean bilirubin blood level was 0.9 +/- 0.96 mg/dL (range: 0.3-1.6) and mean transaminases were 26 +/- 9 and 31 +/- 18 IU/mL (range: 10-44/27-65). After a mean follow-up of 2 years, only one patient has an elevated alanine aminotransferase level without clinical signs of liver disease. Type of pretransplant liver disease did not impact on survival rates. CONCLUSION: In selected cases, an isolated intestinal or a multivisceral graft without a liver can represent a "liver salvage therapy" for an early failing liver in patients with irreversible intestinal failure. Pretransplant liver disease is not a negative prognostic factor.

Adult↗

PubMed2006

Liver transplantation with the Meld system: a prospective study from a single European center.

The efficacy of the Meld system to allocate livers has never been investigated in European centers. The outcome of 339 patients with chronic liver disease listed according to their Meld score between 2003 and 2005 (Meld era) was compared to 224 patients listed during the previous 2 years according to their Child score (Child era). During the Meld era, hepatocellular carcinomas (HCCs) had a 'modified' Meld based on their real Meld, waiting time and tumor stage. The dropouts were deaths, tumor progressions and too sick patients. The rate of removals from the list due to deaths and tumor progressions was significantly lower in the Meld than in the Child era: 10% and 1.2% versus 16.1% and 4.9%, p < 0.05. The 1-year patient survival on the list was significantly higher in the Meld era (84% vs. 72%, p < 0.05). The prevalence of transplantation for HCC increased from 20.5% in the Child to 48.9% in the Meld era (p < 0.001), but between HCCs and non-HCCs of this latter era the dropouts were comparable (9.4% vs. 14.9%, p = n.s.) as was the 1-year patient survival on the list (83% vs. 84%, p = n.s.). The Meld allocation system improved the outcome of patients with or without HCC on the list.

Carcinoma, Hepatocellular↗

PubMed2005

Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. PATIENTS AND METHODS: We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. RESULTS: Tumours were scored as high and low/absent expressers (> or =50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P=0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P<0.001). Vascular invasion was related to tumour recurrence (P=0.025) and to decreased disease free survival (P<0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P=0.01). CONCLUSIONS: Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion.

Adult↗

PubMed2005

Early onset aggressive hereditary amyloidosis: report of an Italian family with TTR Arg47 mutation.

Arg47 is a rare transthyretin-related (TTR) amyloidosis variant that is characterised by polyneuropathy and autonomic failure. We describe an Italian family with this mutation whose members (two women and their father) showed a rapid progression of the peripheral nervous system involvement and died within 5 years of clinical onset. Patients with Arg47 or other aggressive TTR amyloidoses should be considered high priority patients for orthotopic liver transplantation.

Adolescent↗

PubMed2005

Comparison between the fifth and sixth editions of the AJCC/UICC TNM staging systems for hepatocellular carcinoma: multicentric study on 393 cirrhotic resected patients.

AIMS: To compare the prognostic efficacy of the 5th and 6th edition of the TNM staging system for HCC. METHODS: We retrospectively applied the old and the new systems to 393 resected patients, comparing the efficacy of both in prognostic evaluation. RESULTS: The 1-, 3- and 5-year overall survival rates were 89.7, 71.1 and 56.3%, respectively. The 1-, 3- and 5-year disease-free survival rates were 79.4, 54.6 and 39.4%, respectively. Among the factors evaluated, Child's grade B and C (p=0.001) and presence of multiple nodules (p=0.01) were found to be related either to a worse long-term survival or to a worse disease-free survival. Stratifying patient survivals according to the old TNM system, we found significant differences only between stages II and IIIA (p=0.001); otherwise stages I and II (p=0.9) as well as stages IIIA and IVA (p=0.9) showed similar survival rates. Analysing the new TNM system, we found a more homogeneous staging stratification, with significant differences both between stage I and II (p=0.02) and between stage II and IIIA (p=0.05). CONCLUSIONS: In the present multicentric study, long term overall and disease-free survival after liver resection for HCC was strongly affected by the number of tumours and the underlying liver disease. Our results suggest that the new classification appears to achieve an accurate stratification of patients, simpler than the previous edition, as well as a more reliable comparative analysis of outcome after hepatic resection for HCC.

Aged↗

PubMed2005

Use of prosthetic mesh in difficult abdominal wall closure after small bowel transplantation in adults.

Abdominal wall closure after intestinal transplantation in adult patients can be a difficult procedure. The main possibility offered by international experience is the use of myocutaneous flaps and abdominal wall transplantation. We report our experience in intestinal/multivisceral transplantation, including four difficult cases among 27 adult transplant recipients. Three patients underwent prosthetic mesh alone and one, a myocutaneous flap for abdominal closure after primary mesh positioning. We selected a mesh with a structure that allowed us to close the abdomen without creating adhesions and, at the same time, stimulating tissue repair. Two patients experienced local mesh infection, which has been kept under clinical control by antibiotics and daily medications till neoabdominal wall formation. The mesh was then removed. Another patient underwent mesh substitution for a suspicious fever. The last patient had mesh as a bridge for a subsequent myocutaneous flap from the thigh. All patients are in good health with well-functioning grafts and no need for parenteral nutrition. No enterocutaneous fistulae were detected.

Abdominal Wall↗

PubMed2004

Combined heart and liver transplantation in four adults with familial amyloidosis: experience of a single center.

There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy (FAP). The technique for the operation remains to be defined. Four CHLTs were performed for amyloidogenic transthyretin-related (variant Glu89Gln-ATTR Glu89Gln) cardiomyopathy in our center. Patients 1 and 4 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All four patients underwent cardiac and sequential hepatic transplantation with organs procured from the same donor. Venovenous bypass was used in patients 1 and 4 who experienced uncomplicated procedures. The amyloidotic liver of patient 4 was successfully utilized for a domino procedure to treat a patient with hepatocellular carcinoma on cirrhosis. The cardiac performance of patients 1 and 4 remains normal; there has been no progression of amyloidosis at 42 and 1 months after transplantation. Patient 2 had no intraoperative complications but experienced postoperative bleeding, renal failure, sepsis, and heart failure, and finally died of multiorgan failure 2 months after transplant. In patient 3, right hemicolectomy was required intraoperatively due to intestinal ischemia, without significant hemodynamic instability, while extracardiac symptoms of amyloidosis gradually worsened postoperatively. In conclusion, CHLT for ATTR Glu89Gln may be performed even in patients with advanced disease. However, the most compromised patients are more likely to display intraoperative risks, postoperative complications, and worsening of extracardiac, extrahepatic symptoms.

Adult↗

PubMed2004

Efficacy of MELD score in predicting survival after liver retransplantation.

OBJECTIVE: We retrospectively investigated the efficacy of the MELD score to predict the outcome of liver retransplantation and serve as selection criteria. MATERIALS AND METHODS: From 1987 to 2003, the 765 liver transplantations included 87 patients (11.4%) who received a second graft. In addition to graft and patient survivals, ROC curves were used to establish the best MELD score to select cases with poor outcomes. RESULTS: Indications for retransplantation were: 38 (43.7%) surgical complications; 12 (13.8%) chronic rejections; 15 (17.2%) disease recurrences; and 22 (15.3%) primary graft nonfunction. Overall patient survivals at 1, 3, and 5 years were 62.4%, 50.7%, and 49.1%, respectively. A MELD score of 25, calculated by ROC curves, significantly predicted graft and patient survival (44.2% vs 22.5%, P < .05 and 58.6% vs 27.8%, P < .005). During the first 30 postoperative days, patients with a MELD higher than 25 lost the second graft in 48% of cases compared to 16% in the other group (P < .005). Patients retransplanted for primary graft nonfunction showed significant lower 5-year survival rates than those for other indications (28.6% vs 54.5%, P < .05) and higher mean MELD score (30.7 vs 21.9, P < .05). CONCLUSION: A MELD score of 25 is a valid cut-off to predict the outcome of retransplantations, it may be useful to select patients among those who require a second graft. Cases with primary graft nonfunction displayed lower survival, because of their compromised clinical status as evidenced by their high MELD scores.

Algorithms↗

PubMed2003

Review article: liver transplantation for HCC. Treatment options on the waiting list.

The most widely adopted criteria to admit and maintain patients with HCC and cirrhosis in the waiting list for liver transplantation are the Milano criteria, consisting in the presence of a single tumour <or=5 cm in diameter or up to three tumours, none exceeding 3 cm in diameter. Since the average time to transplantation has become longer than 10-12 months in most European and American Centers, the exclusion from the list during the waiting period due to increase of the neoplasm over the established criteria is not uncommon at present. It is mandatory, therefore, to seek an effective therapeutic strategy for patients with HCC waiting for transplantation. Surgical resection and eventual subsequent salvage transplantation seems a cost-effective strategy in resectable HCC. In unresectable neoplasms both transarterial chemoembolization and percutaneous ablation techniques are currently used and one or the other are chosen according to individual applicability, limitations and specific risks. However, although positive trends were reported, no definitive evidence has been produced so far about their efficacy in increasing patient's survival and decreasing tumour recurrence rates after transplantation. Adult-to-adult living donor liver transplantation is one possible way to shorten the waiting list, but this strategy involves important ethical implications. At present it appears justified to take it into consideration only if the waiting time for cadaveric OLT is expected to exceed 7 months. A more general and definitive attempt to overcome problems related to long waiting times for patients with HCC and relatively preserved hepatic function has been introduced in the USA very recently and consists in prioritizing patients with HCC. However, the overall efficacy of this approach will be established only in some years.

Carcinoma, Hepatocellular↗

PubMed2003

Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre.

BACKGROUND: Differences in risk factors for survival and recurrence after liver resection for hepatocellular carcinoma (HCC) in patients with or without cirrhosis are not fully clarified. AIM: To review a single-centre experience of curative liver resections for HCC in order to evaluate clinicopathologic features and the long-term outcome of cirrhotic and noncirrhotic patients. METHODS: From 1981 to 2002, 308 curative liver resections for HCC on cirrhosis (Group 1) and 135 for HCC without cirrhosis (Group 2) were performed. The main demographic, clinicopathologic and operative parameters, as well as early results were analysed and compared. Overall and disease-free survival were evaluated. Prognostic factors for survival and for tumour recurrence were studied by univariate and multivariate analysis. RESULTS: Group 1 had worse preoperative liver function and higher frequency of hepatitis C virus infection. In Group 2, HCC showed larger mean tumour diameter (P < 0.001), poorer differentiation (P < 0.05) and more frequent macrovascular invasion (P < 0.05). Although more extended resections were performed in Group 2 (P < 0.001), there were no differences in blood transfusions, while post-operative complication rate was higher in Group 1 (P < 0.005). After 1992, in-hospital mortality was 2.9% in Group 1 and 1.1% in Group 2 (P = N.S.). The 3- and 5-year overall survival was 63.7% and 42.2% in Group 1, and 67.9% and 51% in Group 2 (P < 0.05). The 3- and 5-year disease-free survival was 49.3% and 27.8% in Group 1, and 58% and 45.6% in Group 2 (P < 0.005). Serum bilirubin level > 1.2 mg/dL, multiple nodules, micro and macrovascular invasion, diaphragm infiltration and blood transfusions independently affected survival in Group 1. Blood replacement was the only negative prognostic factor in Group 2. Independent risk factors for tumour recurrence were satellite nodules and resection performed before 1992 in Group 1, and age < 60 in Group 2. CONCLUSIONS: Despite a more aggressive behaviour, HCC without cirrhosis led to better overall and disease-free survival compared to HCC with cirrhosis after curative liver resection. Age and intra-operative blood transfusions are the only predictors of outcome in patients without cirrhosis. The impact of the latter on long-term survival in both our groups outlines the importance of surgical technique on the results of hepatectomies.

Adult↗

PubMed2001

The effect of aprotinin on renal function in orthotopic liver transplantation.

BACKGROUND: In the European Multicenter Study on the Use of Aprotinin in Liver Transplantation (EMSALT), a randomized, double-blind, placebo-controlled, prospective study, we demonstrated that aprotinin significantly reduces intraoperative blood loss during orthotopic liver transplantation (OLT). Aprotinin is metabolized in the kidney and potentially nephrotoxic at high concentrations. Renal insufficiency is a common and serious complication after OLT. It is unknown whether aprotinin increases the risk of renal failure after OLT. METHODS: We analyzed intraoperative urine output, need for postoperative dialysis, perioperative serum creatinine levels, and creatinine clearance in 93 patients enrolled in EMSALT, receiving a high dose of aprotinin, a regular dose, or placebo. RESULTS: Peak increase in serum creatinine exceeding 0.5 mg/dl during one of the postoperative days occurred in 11 (35%) patients in the placebo group, in 11 (34%) patients in the high-dose group, but only in 1 (3%) patient in the regular-dose group (P=0.007). Furthermore, a perioperative decrease in creatinine clearance was seen in the placebo group (-23.9+/-10.1 ml/min) but not in both high-dose (-1.6+/-13.3 ml/min) and regular-dose (9.7+/-10.3 ml/min) groups (P<0.02 comparing regular-dose and placebo group). CONCLUSIONS: Despite its potential nephrotoxicity, the use of aprotinin for reducing blood loss during OLT does not lead to a higher incidence of postoperative renal insufficiency. In combination with the observed reduction in blood loss, these findings support the prophylactic use of regular-dose aprotinin during OLT.

Aprotinin↗

PubMed2001

Interferon-alpha plus ribavirin and amantadine in patients with post-transplant hepatitis C: results of a pilot study.

BACKGROUND: Recurrence of hepatitis C after liver transplantation is almost constant and may lead to graft loss. The results of treatment with interferon and/or other agents have been controversial. AIMS: To evaluate the efficacy and safety of combination therapy with interferon-alpha2b (3 MU, 3 times weekly), ribavirin (600 mg daily) and amantadine (100 mg daily) in post-transplant hepatitis C. PATIENTS AND METHODS: Enrolled in the study were 9 liver transplant recipients with histologically proven recurrent hepatitis C. Patients were treated for 12 months and followed up for 6 months after treatment. RESULTS: Treatment was not tolerated: only one patient completed the planned course, two stopped therapy within the first 3 months and 6 needed a change. However, mean alanine aminotransferase levels significantly decreased during treatment and were significantly lower than baseline at the end of follow-up. One patient out of 9 (11%) achieved a biochemical and virological sustained response. Control liver biopsy showed improvement in 2/7 patients, no change in 3 and worsening in 2. CONCLUSIONS: In recurrent post-transplant hepatitis C, antiviral treatment with interferon, ribavirin and amantadine seems to be poorly tolerated. However further studies are needed before expressing any conclusion on this potentially important option.

Aged↗

PubMed2001

A revised consideration on the use of very aged donors for liver transplantation.

The upper age limit for organ donation for liver transplantation has increased over the past few years. A retrospective case control study was carried out to evaluate the outcome of 36 liver transplants (group A) performed with grafts procured from donors over 70 years old in the period 1996 to April 2000, matched with 36 transplants (group B) chronologically performed thereafter with organs procured from donors below the age of 40 yr. The groups were comparable as regards main clinical characteristics. Mean follow-up was 14.5 months. Clinical and laboratory parameters of the donors, cold ischemia period, intraoperative blood transfusions, 30-d mortality, incidence of primary graft nonfunction, acute rejection episodes, arterial complications and long-term survival of recipients were considered. The main postoperative biochemical parameters were also collected and compared. A liver biopsy was obtained in 20/36 old donors, revealing less than 25% of steatosis in all but one, which showed steatosis involving 70% of the hepatocytes. There were two postoperative deaths (5.6%) in group A and one (2.8%) in group B (p = NS). Seven postoperative arterial complications (19.4%) occurred in group A, leading to the patient's death because of rupture of the hepatic artery in one case, to successful surgical revascularization in three cases and to retransplantation in three cases. Only one patient in group B (2.8%) experienced hepatic artery thrombosis (p = 0.055). One-year patient survival rates were 77.4% for group A and 88.8% for group B (p = NS); 1-yr graft survival rates were 73.3% for group A and 85.7% for group B (p = NS). In conclusion, donors over 70 should not be excluded a priori for liver transplantation in elective settings. Great attention should be paid to the pathological conditions of arterial vessels caused by atherosclerosis, i.e. the presence of calcified plaques on the hepatic artery, which might represent the source of severe complications.

Adult↗

PubMed2001

Improved results of liver resection for hepatocellular carcinoma on cirrhosis give the procedure added value.

OBJECTIVE: To review a single-center experience to update the performance indexes of liver resection (LR). SUMMARY BACKGROUND DATA: Several therapies have been proposed in the treatment of hepatocellular carcinoma (HCC) on cirrhosis, although LR was the first to be widely applied. METHODS: Of 408 patients with cirrhosis admitted for HCC in the period 1983 to 1998, 264 had a LR. Patient selection, surgical technique, 30-day deaths, long-term survival, recurrence rate, and recurrence treatment were reviewed after stratifying patients according to the year of surgery. Mean follow-up was 34.5 +/- 29.1 months. RESULTS: The number of Child A patients who underwent surgery after the discovery of the tumor at routine evaluation increased significantly from 64.5% to 87.9% during the study period. Procedures carried out without blood transfusions increased from 31.4% to 76.9%. The overall operative death rate was 4.9%. Actuarial survival rates were 63.1% and 41.1% after 3 and 5 years, respectively; actuarial tumor-free survival rates were 49.3% and 27.9% at the same intervals. After 1992, surgical deaths decreased from 9.3% to 1.3%. Actuarial survival rates increased from 52.9% and 32.3% to 71.7% and 49.4% after 3 and 5 years, respectively. There was no difference in the actuarial recurrence rate between the two periods, but the chance to treat recurrence increased over time from 22.4% to 53.7% with a concomitant, significant improvement in survival. CONCLUSIONS: LR represents a well-established therapy for HCC on cirrhosis. It remains one of the fundamentals in the multidisciplinary approach to this tumor and should be considered as the first option for patients with preserved hepatic function and limited disease. Today, LR should offer a surgical death rate of less than 1.5%, a 5-year survival rate of approximately 50%, and a 5-year tumor-free survival rate of 28% when performed in specialized centers.

Adult↗