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There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

Background Leiomyosarcomas (LMS) of the inferior vena cava (IVC) originate in the retrohepatic (RHVC) portion in 15% of cases.1 Due to complex anatomy and need to preserve venous outflow from the infra-diaphragmatic viscera, the operation may require total vascular exclusion, veno-venous bypass and hypothermic liver resections.2,3 In this video, virtual planning of the operation allowed a parenchyma-sparing radical resection in a patient with limited liver reserve. Methods A 12-cm LMS of RHVC invading the entire segment 1 (i.e., Spiegel’s lobe, paracaval portion, and caudate process) was diagnosed in a man with metabolic steato-hepatitis (BMI: 34). He had no response to previous chemotherapy. Major hepatectomy was excluded considering the high risk of postoperative liver failure. 3D-reconstruction of regional anatomy allowed planning of a parenchymal-sparing, en bloc resection of tumor, RHVC, and caudate lobe while avoiding hilar and suprahepatic venous clamping. Results The operation strategy relied on the en bloc separation of caudate lobe, RHVC, and tumor from the hepatic veins confluence and the posterior segments after complete mobilization of the liver. Vessel loop-assisted hanging maneuver, encircling tumor, and RHVC with superimposed 3D-reconstructions guided the parenchymal transection, while preserving the middle hepatic vein outflow. RHVC was replaced with prosthetic material. Conclusions Complex resection of primary tumor of the IVC en bloc with caudate lobe and RHVC can be attempted in chronic liver diseases at-risk of postoperative failure. Preservations of transhepatic flow and liver function depends on tumor size and preservation of noninvaded hepatic-veins confluence. Preoperative virtual 3D reconstruction is crucial in surgical planning.

Summary Background Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging. Methods We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18–65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov , NCT01387503 . Findings Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4–11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60–85). 5-year tumour event-free survival was 76·8% (95% CI 60·8–96·9) in the transplantation group versus 18·3% (7·1–47·0) in the control group (hazard ratio [HR] 0·20, 95% CI 0·07–0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9–97·1) in the transplantation group versus 31·2% (16·6–58·5) in the control group (HR 0·32, 95% CI 0·11–0·92; p=0·035). The most common registered grade 3–4 serious adverse events were hepatitis C virus recurrence (three [13%] of 23 patients) and acute transplant rejection (two [9%]) in the transplantation group, and post-embolisation syndrome (two [9%] of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation). Interpretation Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria. Funding Italian Ministry of Health.

Major concerns about donor morbidity and mortality still limit the use of living donor liver transplantation (LDLT) to overcome the organ shortage. The present study assessed donor safety in LDLT in Italy reporting donor postoperative outcomes in 246 living donation procedures performed by 7 transplant centers. Outcomes were evaluated over 2 time periods using the validated Clavien 5-tier grading system, and several clinical variables were analyzed to determine the risk factors for donor morbidity. Different grafts were obtained from the 246 donor procedures (220 right lobe, 10 left lobe, and 16 left lateral segments). The median follow-up after donation was 112 months. There was no donor mortality. One or more complications occurred in 82 (33.3%) donors, and 3 of them had intraoperative complications (1.2%). Regardless of graft type, the rate of major complications (grade ≥ 3) was 12.6% (31/246). The overall donor morbidity and the rate of major complications did not differ significantly over time: 26 (10.6%) donors required hospital readmission throughout the follow-up period, whereas 5 (2.0%) donors required reoperation. Prolonged operative time (>400 minutes), intraoperative hypotension (systolic < 100 mm Hg), vascular abnormalities, and intraoperative blood loss (>300 mL) were multivariate risk factors for postoperative donor complications. In conclusion, from the standpoint of living donor surgery, a meticulous and well-standardized technique that reduces operative time and prevents blood loss and intraoperative hypotension may reduce the incidence of donor complications. Transparency in reporting results after LDLT is mandatory, and we should continue to strive for zero donor mortality. Liver Transplantation 23 184–193 2017 AASLD.

Determine the histologic response-rate (complete versus partial tumor extinction) after single radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC) arising in cirrhosis. Investigate possible predictors of response and assess efficacy and safety of RFA as a bridge to liver transplantation (OLT).RFA has become the elective treatment of local control of HCC, although histologic data supporting radiologic assessment of response are rare and prospective studies are lacking. Prognostic impact of repeated RFA for HCC persistence is also undetermined.Percentage of RFA-induced necrosis and tumor persistence-rate at various intervals from treatment was studied in 60 HCC (median: 3 cm; Milan-Criteria IN: 80%) isolated in 50 consecutive cirrhotic patients undergoing OLT. Single-session RFA was the only treatment planned before OLT. Histologic response determined on explanted livers was related to 28 variables and to pre-OLT CT scan.Mean interval RFA--OLT was 9.5 months. Post-RFA complete response rate was 55%, rising to 63% for HCC/=3 cm. Tumor size was the only prognostic factor significantly related to response (P = 0.007). Tumor satellites and/or new HCC foci (56 nodules) were unaffected by RFA and significantly correlated with HCC3 cm (P = 0.05). Post-RFA tumor persistence probability increased with time (12 months: 59%; 18 months: 70%). Radiologic response rate was 70%, not significantly different from histology. Major post-RFA morbidity was 8%. No mortality, Child deterioration, patient withdrawal because of tumor progression was observed. Post-OLT 3-year patient/graft survival was 83%.RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (3 cm) and time from treatment (1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.

Background. Insulin resistance is a key factor in the pathogenesis of hepatogenous diabetes and influences the prognosis of chronic liver diseases. In vivo assessment of insulin resistance in humans is expensive; therefore, surrogate indices based on a fasting plasma glucose and insulin concentrations (HOMA-IS, QUICKI) were proposed. This study aimed to test whether these simple indices are reliable measures of insulin sensitivity in patients with liver cirrhosis before and after liver transplantation (LTx). Methods. HOMA-IS and QUICKI were compared with insulin sensitivity as assessed with the gold standard technique (insulin clamp) in 20 patients with liver cirrhosis, in 36 patients after LTx, and in 25 matched healthy subjects (predominantly men). To test whether these indices may be applied also in prospective studies, 10 patients with liver cirrhosis were studied longitudinally before and 2 years after LTx. Results. Both HOMA-IS and QUICKI were associated with insulin sensitivity in patients with liver cirrhosis (r =0.63, P =0.005 and r =0.60, P =0.009) and in LTx patients (r =0.41, P =0.02 and r =0.46, P =0.05). Both were able to detect the improvement of insulin sensitivity after LTx in the patients studied prospectively. Conclusions. HOMA-IS and QUICKI are simple reliable tools to assess insulin sensitivity in clinical and epidemiologic investigations of chronic liver disease before and after LTx.

Cirrhotic patients after liver transplantation show a near-normal glucose homeostasis when in stable condition. In contrast, the basal and insulin-mediated whole-body protein metabolism remain altered several years after the graft. To examine whether the persisting defect of protein metabolism was due to the muscle, 7 non-diabetic liver-transplanted patients in stable condition were studied by means of the catheterization of the brachial artery and the deep forearm vein (to measure the balance across the forearm) and the infusion of labelled leucine and phenylalanine associated with indirect calorimetry. Whole-body proteolysis (as determined by endogenous leucine flux, ELF), protein synthesis (from non-oxidative leucine disposal, NOLD) and leucine oxidation (LO) were reduced in comparison to previously obtained values in a normal population. Insulin infusion (while maintaining euglycemia) induced a not significant variation of forearm phenylalanine Ra (24.4--16.5 micromol/100 ml forearm min(-1); proteolysis) and Rd (18.5--19.7; protein synthesis). In contrast, the whole-body insulin-dependent inhibitions of ELF (31.5--21.8 micromol/m(2) min) and NOLD (27.3--18.4) were impaired with respect to a normal population. On the basis of the present results, we conclude that skeletal muscle is not responsible for the alterations of leucine metabolism persisting after liver transplantation. By exclusion, this points to the liver as the major determinant of the leucine metabolism defect.

The "Fondazione IRCCS Istituto Nazionale dei Tumori" ( National Tumour Institute) in Milan (Italy) offers mediation services aimed at restoring communication between patients and healthcare professionals, when their relationship has been altered by a conflict during the diagnosis or treatment process. A method derived from transformative mediation is used. The purpose of mediation is not to examine clinical aspects, nor to identify who is right and who is wrong. Individual sessions are often sufficient to reduce litigation.

Diabetes mellitus frequently complicates cirrhosis but the pathogenic mechanisms are unknown. To assess the contribution of reduced insulin action and secretion, 24 cirrhotic-diabetic patients waiting for liver transplant because of an unresectable hepatocarcinoma underwent an oral glucose tolerance test (OGTT) to assess the beta-cell function and an insulin clamp combined with [3-(3)H]glucose infusion to measure whole body glucose metabolism before and 2 years after the transplant. Seven cirrhotic nondiabetic patients, 11 patients with chronic uveitis on similar immunosuppressive therapy, and 7 healthy subjects served as control groups. Cirrhotic patients showed a profound insulin resistance, and diabetics in addition also showed increased endogenous glucose production (P

Prototypes of Gianturco-Rosch Z-stents coated with polycarbonate urethane (PCU) were placed in the biliary tree of pigs, in order to test their biomechanical behavior, stability, and biocompatibility.The stents were surgically implanted in the common bile duct of three pairs of pigs, which were killed after 1, 3, and 6 months respectively. Explanted livers from pigs of the same race, age, and size were used to provide comparative data. The bile ducts were radiologically and histopathologically examined; the stents were processed and examined by scanning electron microscopy.No complications occurred and the animals showed a normal weight gain. The main bile duct appeared radiologically and macroscopically dilated, but the stents proved to be in place. Histologically, the bile duct epithelium was destroyed, but neither hyperplastic nor inflammatory fibrotic reactions of the wall were evident. Both the metallic structure and the polymeric coating of the stents were intact. A layer of organic material with a maximum thickness of approximately 3 micron was evident on the inner surface of the stents.The present in vivo study demonstrates the biocompatibility, efficacy, and stability of PCU-coated Gianturco-Rosch stents in the biliary environment.

BACKGROUND For patients with surgically untreatable neuroendocrine tumors (NETs), the optimal therapeutic approach remains undefined. Somatostatin analogs and interferons have failed to control neoplastic growth, and chemotherapy has been only moderately more effective. The authors' previous study of the combination of 5-fluorouracil (FU), dacarbazine (DTIC), and epirubicin (EPI) (the FDE regimen) documented good tolerability, but the results for tumor growth control were disappointing. In an attempt to improve these results, the authors conducted a preliminary trial of an intensified FDE regimen (FU 500 mg/m2 administered intravenously [i.v.], DTIC 200 mg/m2 i.v., and EPI 30 mg/m2 i.v. on Days 1, 2, and 3 every 3 weeks). METHODS Thirty NET patients (15 male, 15 female; median age, 55 years; age range, 19-72 years) were enrolled, none of whom had previously been given chemotherapy. The histologic types of disease were gastroenteropancreatic (GEP) tumors (n = 21, 6 carcinoid tumors and 15 pancreatic NETs), other carcinoid tumors (n = 3), other NETs (n = 4), medullary thyroid carcinoma (MTC) (n = 1), and Merkel cell carcinoma (n = 1). Six patients had a syndrome related to endocrine hypersecretion. One hundred fifty-four therapy cycles were delivered (median, six per patient), and all patients could be evaluated for response on the basis of intent-to-treat analysis. RESULTS There were 9 objective responses: 2 complete responses (in 1 patient with Merkel cell carcinoma and 1 with pancreatic NET) and 7 partial responses (in 3 patients with pancreatic NETs, 2 with other NETs, 1 with GEP carcinoid tumor, and 1 with MTC). The median duration of response was 10 months (range, 5+ to 24+ months). No reduction in symptoms was achieved among the six patients with endocrine hypersecretion syndrome. Levels of urinary 5-hydroxyindoleacetic acid and serum chromogranin A were decreased in 50% and 14% of patients, respectively, who presented with abnormal baseline values. Treatment toxicity was acceptable and included nausea and vomiting, alopecia, leukopenia, and mucositis. CONCLUSIONS This trial demonstrated that the FDE regimen may be at least as effective as other systemic regimens. Comparison of this experience with the authors' previous trial revealed a noteworthy increase in the activity of the intensified regimen, especially in GEP NETs (the most chemoresistant tumors). Continued clinical research to improve these results is highly justified. Cancer 1998;83:372-378. © 1998 American Cancer Society.

A series of 132 patients who underwent liver transplantation for primary liver cancer was collected from three different Italian hospitals and studied for recurrence of hepatocellular carcinoma after liver replacement. Twenty-one patients (15.9%) had a neoplastic recurrence after an average follow-up period of 7.8 months after transplantation (range, 1–25 months); 15 (71%) occurred within the first 18 months after transplant and only two recurred later than 2 years. The sites of recurrence were grafted liver (19%), lung (19%), bone (14%), and other (5%). Eight patients (38%) had multiple organ involvement at the onset. After 1, 2, 3, and 4 years the overall survival rates were 62%, 43%, 29%, and 23%, respectively. The tumor factors related to early cancer recurrence after transplantation were diameter of nodules more than 3 cm (P < 0.05), tumor stage not meeting the "Milan criteria" (P < 0.03), and presence of peri-tumoral capsule (P < 0.05); the number of nodules, TNM stage, presence of vascular invasion, alpha-fetoprotein level more than 150 UI/l, pre-transplant chemoembolization and resectability of cancer deposits did not seem to be related to early recurrence. The prognosis differed in the 7 patients with resectable recurrences (57% 4-year survival) and the 14 patients with unresectable disease (14% 4-year survival) (P < 0.02). Better patient selection and new combined medical strategies could reduce the incidence of and mortality from liver cancer recurrence after transplantation. The role of surgical resection of recurrence should be further investigated.

This study investigated the psychosocial adjustment in 40 patients who received orthotopic liver transplantation (OLT)for several endstage liver diseases. Twenty patients were grafted because they suffered from liver cancer as well as cirrhosis. Particular attention was paid to evaluating whether cancer could affect recipients' coping with transplant. Each patient underwent a semi-structured interview to obtain information on their psychosocial life, relationship with the donor, organ acceptance and life expectancy. Interview was performed I year after transplantation. A psychodiagnostic evaluation was also performed using a Minnesota Multiphasic Personality Inventory (MMPI) and a Human Figure Test. Psychosocial adaptation in everyday life following liver transplantation seemed good in most of the patients, whatever the indication for transplantation might be. It can be seen that by replacing the diseased organ a high percentage of oncological patients overcame their fear of cancer.

The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult.We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation.The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival.Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.

Background. The prognosis for colorectal cancer patients is related closely to the extent of tumor at the time of diagnosis, and early detection of metastatic or recurrent disease is an important prerequisite for successful treatment. Radioimmunodetection is a relatively new technique to image colorectal cancer using radiolabelled monoclonal antibodies (MoAb). The goal of this study was to evaluate the clinical use of radioimmunodetection with the anticarcinoembryonic antigen MoAb FO23C5, radiolabelled with 131 I, in patients submitted to surgery for colorectal cancer and with suspected local recurrences

Several retrospective analyses have recently shown the advantage of liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) at early tumor stages. Preliminary results of a prospective series of OLT for unresectable small HCC arising in cirrhosis are reported. Eighteen out of 22 patients (82%) are alive without evidence of HCC recurrence after a median follow-up of 11 months.

There are only a few experimental investigations on the feasibility and potential advantages of intraportal nutrition in animals and only two uncontrolled studies in humans. The purpose of this study was to compare some metabolic variables in patients who received portal or systemic nutrition after elective surgery for colorectal cancer. Twenty patients were randomized to receive postoperatively for a week a hypocaloric, "protein sparing" standard infusion via the portal (catheter in the gastroepiploic vein) (10 patients) or systemic (10 patients) route. We evaluated the basal concentrations of some visceral and acute-phase proteins and their variations in the first postoperative week and the nitrogen balance. Statistical analysis was performed by the two-tailed Student t test. There was no difference in the daily changes of the visceral and acute-phase proteins after surgery in the two groups of patients, but in the portal group there was a significantly better recovery of the level of total protein, albumin, and cholinesterase at the end of the portal infusion vs the systemic group (por = .005, .03, and .02, respectively). In regard to the nitrogen balance, although there was no difference in the overall balance between portal and systemic nutrition, if we separate the acute phase of the injury from the later one we do not see any significant difference in the first period but we do see a highly significant advantage for the portal group during the last 2 days (por = .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred forty-four cancer patients harboring a central venous catheter (CVC) were prospectively investigated to assess the relationship between hub culture, clinical assessment of sepsis before removal, and CVC sepsis. In 22 patients, the CVC was removed because of clinical assessment of catheter sepsis expressed by the staff prior to the removal. For each CVC removal, peripheral blood (qualitative method), hub, and CVC tip (quantitative method) cultures were performed. Clinical sepsis (disappearance of fever after CVC removal) was observed in 13 patients, microbiologic "sepsis" (identification of the same microorganisms on the CVC tip and in the peripheral blood) in seven patients, and clinical and/or microbiologic sepsis in 16 patients. Staphylococcus epidermidis was the microorganism most frequently identified. Hub culture was negative in 48% and positive for a low number and a high number of colonies in 35% and 17%, respectively. The predictive value of hub culture was 96% when testing negative and 8% and 37% (p = 3 x 10(-3)) when testing positive for a low and a high number of colonies, respectively. Predictive values of clinical assessment were 55% if positive and 97% if negative. Combining hub cultures and clinical assessment, the risk of sepsis varied from 2% with both evaluations negative to 89% in the case of positive clinical assessment associated with positive high-count hub. Inasmuch as the CVCs used have a disposable hub, it is possible to have an accurate diagnosis of CVC sepsis without removing the CVC.

Inferior vena cava thrombosis after liver transplantation is uncommon. We describe a case of this unusual complication occurring after piggy-back (end-to-side) graft implantation. Renal failure, lower limb edema, and hemodynamic instability were the presenting symptoms requiring immediate surgical correction with a left renal-to-splenic vein shunt over a ringed 2.5-cm prosthesis. The decision to go ahead with the shunt was preceded by an intraoperative confirmation of a 10-cm H2O pressure gradient between the caval and portal circulations. This gradient, unlike that observed in liver cirrhosis, ultimately turned a splenorenal shunt into a renal-splenic one. Six months after the procedure, the patient is alive and well with normal liver and renal function. The technique described may be useful in the management of other clinical conditions of acute infrahepatic caval hypertension.

The number of women who decide to have a child after organ transplantation has increased. We determined the outcomes of 67 pregnancies of women who had undergone kidney, liver or heart transplantation. All recipients had been maintained on immunosuppressive therapy before and during pregnancy. Pregnancy complications at term were observed in 17 out of 67 women (25%), hypertension being the most frequent complication (16.17%). Two transplant rejections were reported. Sixty-eight infants were delivered (including one pair of twins); five women had two pregnancies at term. Twenty-eight miscarriages (29.2%) were recorded. Of these 68 babies (including the pair of twins), 40 (58.8%) were born at term and 28 (41.2%) before term. The babies were followed-up for 2 months to 13 years. According to our previous experience, our study shows that patients who have undergone organ transplantation can give birth to healthy infants as long as they are monitored accurately during pregnancy.

Heat shock proteins (HSP) from tumor cells contain the gp96 polypeptide associated with cancer-specific antigenic peptides. Mice that are immunized with HSP/peptide-complex (HSPPC) derived from cancer tissue reject tumor from which HSPs are purified. We tested in humans whether vaccination with HSPPC-gp96 (Oncophage) from autologous liver metastases of colorectal carcinoma induces cancer-specific T-cell responses in patients rendered disease free by surgery.Twenty-nine consecutive patients underwent radical resection of liver metastases [Memorial Sloan-Kettering Cancer Center (MSKCC) score 1-3 (good prognosis), 18 patients; score 4-5 (bad prognosis), 11 patients] and received autologous tumor-derived HSPPC-96. Two vaccine cycles were administered (four weekly injections followed by four biweekly injections after 8 weeks). Class-I HLA-restricted, anti-colon cancer lines T-cell response was measured by ELISPOT assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Feasibility, safety, and possible clinical benefits were also evaluated.Either a de novo induced or a significant increase of preexisting class I HLA-restricted T-cell-mediated anti-colon cancer response was observed in 15 (52%) of 29 patients. Frequency of CD3+, CD45RA+, and CCR7- T lymphocytes increased in immune responders. No relevant toxicity was observed. As expected, patients with good prognosis had a significantly better clinical outcome than those with poor prognosis [2-year overall survival (OS), 89 versus 64%, P = 0.001; disease-free survival (DFS), 46 versus 18%, P = 0.001]. Patients with immune response had a statistically significant clinical advantage over nonresponding subjects (2-year OS, 100% versus 50%, P = 0.001; DFS, 51% versus 8%, P = 0.0001). Occurrence of immune response led to better tumor-free survival, whatever the predicted prognosis was (hazard ratio, 0.11-0.12 with/without stratification; P = 0.0012-0.0003).HSPPC-96 vaccination after resection of colorectal liver metastases is safe and elicits a significant increase in CD8+ T-cell response against colon cancer. In this limited number of patients, two-year OS and DFS were significantly improved in subjects with postvaccination antitumor immune response, independently from other clinical prognostic factors.

Background. Insulin resistance is a key factor in the pathogenesis of hepatogenous diabetes and influences the prognosis of chronic liver diseases. In vivo assessment of insulin resistance in humans is expensive; therefore, surrogate indices based on a fasting plasma glucose and insulin concentrations (HOMA-IS, QUICKI) were proposed. This study aimed to test whether these simple indices are reliable measures of insulin sensitivity in patients with liver cirrhosis before and after liver transplantation (LTx). Methods. HOMA-IS and QUICKI were compared with insulin sensitivity as assessed with the gold standard technique (insulin clamp) in 20 patients with liver cirrhosis, in 36 patients after LTx, and in 25 matched healthy subjects (predominantly men). To test whether these indices may be applied also in prospective studies, 10 patients with liver cirrhosis were studied longitudinally before and 2 years after LTx. Results. Both HOMA-IS and QUICKI were associated with insulin sensitivity in patients with liver cirrhosis (r=0.63, P=0.005 and r=0.60, P=0.009) and in LTx patients (r=0.41, P=0.02 and r=0.46, P=0.05). Both were able to detect the improvement of insulin sensitivity after LTx in the patients studied prospectively. Conclusions. HOMA-IS and QUICKI are simple reliable tools to assess insulin sensitivity in clinical and epidemiologic investigations of chronic liver disease before and after LTx

We report a 1-year patient and graft survival after combined liver-pancreatic islet transplantation. The patient was affected by a pancreatic neuroendocrine carcinoma with extensive liver metastasis. Native vancreas and total liver removal was undertaken after a good response to chemotherapy, and the patient was still cancer-free 1 year later. Normal liver function and insulin independence was achieved, although islet response to glucose challenge remained delayed. Immunosuppression was maintained with cyclosporin mono therapy.

Background: Hypermetabolism, insulin resistance, and diabetes are common in patients with liver cirrhosis. Objective: We assessed whether diabetes and insulin resistance influence postabsorptive energy homeostasis in these patients and whether liver transplantation (LTx) and immunosuppressive drugs affect these relations. Design: Twenty-six patients with liver cirrhosis (16 with and 10 without diabetes) were studied with an insulin clamp and indirect calorimetry. Eleven of these subjects were studied 9 mo after LTx to longitudinally assess its effects. To cross-sectionally explore a longer follow-up period, we studied 65 patients 6, 14, and 32 mo after LTx. Seven patients with chronic uveitis (receiving immunosuppressive therapy) and 20 healthy subjects served as control subjects. Results: Diabetic and nondiabetic patients with cirrhosis had insulin resistance (SI(clamp); P < 0.03) and higher measured resting energy expenditure (REE) as a percentage of predicted REE than did healthy subjects (107.6 ± 1.8% compared with 97.4 ± 2.3%; P < 0.03), and these 2 alterations were associated (R 2 = 0.119, P = 0.0002). The longitudinal study showed an improvement in the 2 variables after LTx, but full restoration was not achieved. The cross-sectional analysis confirmed this observation in patients studied 6 mo (n = 28) after LTx. In patients studied 14 (n = 21) and 32 mo (n = 16) after LTx, SI(clamp) and measured REE as a percentage of predicted REE were not significantly different from those in control subjects. Conclusions: In patients with liver cirrhosis, higher-than-normal postabsorptive REE was associated with insulin resistance regardless of diabetes. This abnormality persisted in patients studied 6‐9 mo after LTx but improved simultaneously with the improvement in insulin sensitivity thereafter. Am J Clin Nutr 2002;76:541‐8.

LIVER metastases from neuroendocrine tumors (NET) is the main cause of death for patient with neuroendocrine tumors originating from the intestine and pancreas. In about 90% of patients, the distribution of liver metastases is multifocal and bilateral so that curative liver resection is feasible in no more than 20% of the referred cases. Large liver metastases often cause hormone-related symptoms (carcinoid syndrome) with severe consequences on patient quality of life. Both surgical and medical treatments have been proposed for patients with liver metastases from NET (systemic and intraarterial chemotherapy, somatostatin analogues, interferon therapy) with cumulative patient survival not exceeding 25 to 35% at five years. Resective surgery with curative intent has been associated with an improved 5 year survival in nearly 50% of cases, but the number of eligible patients is low. Total hepatectomy and liver transplantation (OLT) has been advocated for patients with bilateral unresectable symptomatic liver metastases from NET although a clear consensus on stage of disease, pathological subtypes, and patient conditions amenable of transplant candidacy are still lacking. In this report, we describe our experience with 29 patients affected by liver metastases from NET who were treated with either hepatic resections or liver transplantation. Pre-transplantation selection criteria currently applied in our centre are also proposed.

To study retinol binding protein variation in the serum of patients who have undergone liver transplantation.Retinol binding protein was retrospectively determined by the immunonephelometric method on serum from 14 patients who had undergone orthotopic liver transplantation 2 weeks after the surgery and then once a month during the first year posttransplantation. The patients were divided into two groups on the basis of early (first 10 days) postoperative graft function: group I, 6 patients with severe ischemic damage; and II 8 patients with moderate-severe liver dysfunction.The men retinol binding protein level at one year of follow-up was persistently higher in group I than in group II (83.1 +/- 33.4 vs 44.6 +/- 20.7 mg/L, p0.001). Interestingly, retinol binding protein levels remained higher in patients of group I event when the other biochemical parameter of liver function returned to normal. The increase in retinol binding protein serum levels was independent of variation in other parameters of liver and kidney function, but was correlated with an increase in transthyretin and retinol levels.Our results show a close relationship between a permanent high retinol binding protein level and severe graft injury after liver transplantation. However, the mechanism underlying the increase remains to be defined.

C IRRHOSIS caused by hepatitis C virus (HCV) accounts for at least 30% of all liver transplants (OLT) currently performed in adults.’ Good survival of patients with such an indication has been described, even though the reappearance of viral genome (HCV-RNA) occurs in more than 90% of patients during the first year after transplantation.‘.’ The course of recurrent HCV graft infection is generally benign. Nevertheless, some concerns about the long-term outcome of the disease have arisen since at least 50% of HCV-RNA positive patients develop chronic hepatitis within two years’,2 and 35% of livers are seriuosly injured (chronic active hepatitis and cirrhosis) 5 years after transplantation.4 In the present study, a therapeutic attempt to prevent recurrent HCV infection was undertaken in a group of HCV-RNA positive transplant recipients, using a combination of interferon and ribavirin early after OLT. The preliminary results of this pilot experience, the first of its kind, are reported herein.

206 THE UN-SUSTAINABLE MATCH IN HCV LIVER TRANSPLANT PATIENTS A.W. Avolio, S. Agnes, M.C. Lirosi, M. Salizzoni, A. Pinna, B. Gridelli, L. De Carlis, M. Colledan, G. Gerunda, U. Valente, G. Rossi, G. Ettorre, A. Risaliti, V. Mazzaferro, F. Bresadola, M. Rossi, G. Tisone, F. Zamboni, L. Lupo, O. Cuomo, F. Calise, A. Vitale, N. Nicolotti, R. Romagnoli, A. Cucchetti, S. Gruttadauria, I. Mangoni, D. Pinelli, R. Montalti, M. Gelli, L. Caccamo, G. Vennarecci, D. Nicolini, E. Regalia, U. Baccarani, Q. Lai, T. Manzia, E. Tondolo, M. Rendina, A. Perrella, E. Scuderi, B. Antonelli, C. de Waure, M. Angelico, P. Burra, A. Gasbarrini, U. Cillo, Donor-to-Recipient Italian Liver Transplant (DR2-ILTx) Study Group. Liver Transplant Center, “A.Gemelli”Hospital, Catholic University, Rome, Liver Transplant Center, “S. Giovanni Battista” Hospital, University of Turin, Turin, Liver Transplant Center, “S. Orsola” Hospital, University of Bologna, Bologna, Liver Transplant Center, IsMeTT-UPMC, Palermo, Liver TransplantCenter, “Niguarda” Hospital, Milan, Liver Transplant Center, “Ospedali Riuniti”, Bergamo, Liver Transplant Center, University of Modena and Reggio Emilia, Modena, Liver Transplant Center, “S. Martino” Hospital, University of Genoa, Genoa, Liver Transpantation Center, IRCCS Foundation, “Maggiore” Hospital, Milan, Liver Transplant Center, “San Camillo-Forlanini” Hospital, Rome, Liver Transplant Center, “Umberto I” Hospital, Polytechnic University of Marche, Ancona, Liver Transplant Center, National Cancer Institute, IRCCS Foundation, Milan, Liver Transplant Center, University of Udine, Udine, Liver Transplant Center, “Umberto I” Hospital, “La Sapienza” University, Liver Transplant Center, “Tor Vergata” University Hospital, Rome, Liver Transplant Center, “G. Brotzu” University Hospital, Cagliari, Liver Transplant Center, Department of Emergency and Organ Transplant, University of Bari, Bari, Liver Transplant Center, Laparoscopic Hepatobiliary Surgical Unit, “A. Cardarelli” University Hospital, Liver Transplant Center, Hepatobiliary Surgical Unit, “A. Cardarelli” University Hospital, Naples, Liver Transplant Center, Department of Surgical and Gastroenterological Sciences, University of Padua, Padova, Epidemiology and Biostatistics Unit, Institute of Hygiene, Catholic University, Rome, Italy E-mail: alfonso.avolio@tin.it

The assessment of biological markers as potential indicators of disease aggressiveness is still an open problem in hepatocellular carcinoma. Cell proliferation and extracellular matrix (ECM)-associated antigens and tumor-cell products can be associated with clinical aggressiveness in this tumor type, as has already been demonstrated for others. Cell proliferation, expressed as the in vitro [3H]thymidine labeling index, and ECM-associated antigens, such as type IV collagenase and laminin receptors, were assessed on the same paraffin-embedded samples. A strong association (P = 0.0001) was observed between the expression of collagenase and laminin receptors, with a correlation coefficient (rs) of 0.68. No relationship was found between cell proliferation and ECM-associated antigens. Moreover, the biological markers were generally independent of clinicopathologic features, except for a higher number of collagenase- and laminin receptor-positive cells in large (≥ 5 cm) compared with small (< 5 cm) tumors. In the present series of hepatocellular carcinoma patients, the 3-year clinical outcome was significantly affected by cell proliferation and ECM-associated antigens. © 1993 Wiley-Liss, Inc.

Catecholamines are involved critically in the mechanisms of liver cell proliferation by acting on hepatic alpha-1 and beta-2 adrenoceptors. To identify the role of these receptors in human hepatocellular carcinoma (HCC), the density was examined of alpha-1 and beta-2 adrenoceptors with their affinity and coupling of beta-2 adrenoceptors to adenylate cyclase in HCC tissue and in nonadjacent/nontumor tissue from the same livers. Studies were also done on healthy livers from age-matched and sex-matched patients undergoing abdominal surgery for nonhepatic diseases. Twenty-two HCC had a decrease of about 72% in alpha-1 adrenoceptor density compared with their nonadjacent/nontumor tissue and a decrease of about 40% compared with healthy controls. Nonadjacent/nontumor tissue from HCC patients had a 125% increase in alpha-1 adrenoceptor density compared with healthy livers. Twenty-three of 24 HCC had an increase of about 180% in beta adrenoceptor density compared with their nonadjacent/nontumor tissue and healthy controls. Beta adrenoceptors were coupled to adenylate cyclase, as evidenced by a guanosine triphosphate-mediated right shift in (-)-isoproterenol competition isotherms and by cyclic adenosine monophosphate (cAMP) production after stimulation with (-)-isoproterenol. The HCC tissue yielded a larger increase in cAMP than nonadjacent/nontumor tissue and healthy controls. The authors conclude that a higher density of alpha-1 adrenoceptors in nonadjacent/nontumor tissue from HCC characterizes the "healthy" part of the liver in HCC patients and that an increase in beta-2 and a decrease in alpha-1 adrenoceptor densities characterize the tumor part of the liver in human HCC.

Ten patients harboring an indwelling CVC with contamination of the infusate are described. Six patients developed sepsis, which was resolved in all patients except one who died from misdiagnosed septic shock. The majority of microorganisms responsible for the infusate contamination were opportunistic pathogens and in five cases were S. epidermidis. There was no apparent correlation between contamination rate of the infusate and subsequent sepsis of the patients. Reasons for the high prevalence of Staphylococcus epidermidis include ubiquitous diffusion of this microorganism, marked affinity for prosthetic devices, especially by the slime-producing strains, and increased susceptibility of debilitated cancer patients to infection. Recognition that the possibility exists for infusate contamination during compounding should alert all members of the Nutritional Support Team to use aseptic technique when preparing and handling the intravenous solutions. Infusate-related sepsis is a potentially lethal but preventable event.