Laparoscopic approach for down-staging in hepatocellular carcinoma patients who are candidates for liver transplantation.

INTRODUCTION: The aim of this study was to assess the impact of laparoscopic thermoablation (LTA) and laparoscopic resection (LR) as neoadjuvant therapy before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). METHODS: From June 2005 to November 2010, 50 consecutive patients affected by HCC with liver cirrhosis were treated with LTA under ultrasound guidance or LR. Of them, 10 patients (mean age, 58.3 ± 5.59 years; male:female, 8:2) underwent OLT. They were mostly Child-Pugh class A (80%). RESULTS: A LTA of 12 nodules was achieved in 7 patients and an LR of 3 HCC nodules in the other 3 subjects. The mean length of surgery was 163 minutes (range; 60-370). The mean hospital stay was 6.1 days. Transient mild postoperative liver failure was reported in 1 case. Complete tumor necrosis was observed in 10 thermoablated nodules (83.3%) via spiral computerized tomographic scan at 1 month after treatment; the resected patients showed absence of recurrence. All patients underwent OLT after a mean interval of 7 months. The histology of the native liver showed complete necrosis in 9/12 thermoablated nodules (75%); a recurrence at surgical site occurred in 1 patient in the resection group. CONCLUSIONS: Laparoscopic ultrasound can be used in potential OLTs candidates to accurately stage HCC in advanced cirrhosis with minimal morbidity. LTA and LR proved to be safe and effective techniques for HCC patients, representing a valid "bridge" to OLT.

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.

Italian experience in adult clinical intestinal and multivisceral transplantation: 6 years later.

PATIENTS AND METHODS: Between December 2000 and November 2006, 28 isolated intestinal transplants and nine multivisceral transplants (five with liver) from cadaveric donors have been performed for short gut syndrome (n = 15), chronic intestinal pseudo-obstruction (n = 10), Gardner's syndrome (n = 9), radiation enteritis (n = 1), intestinal atresia (n = 1), and massive intestinal angiomatosis (n = 1). Indications for transplantations were: loss of venous access, recurrent sepsis due to central line infection, and/or major electrolyte and fluid imbalance. Liver dysfunction was present in 19 cases. All patients were adults of median age at transplant of 34.7 years and mean weight 59.6 kg. All recipients were on total parenteral nutrition for a mean time of 38.8 months. Mean donor/recipient body weight ratio was 1.1. RESULTS: The mean follow-up was 892 +/- 699 days. Twenty-five patients were alive (67.5%) with 3-year patient survivals of 70% for isolated intestinal transplantations and 41% for the multivisceral transplantations (P = .01). The mortality rate was 32.5% with losses due to sepsis (63%) or rejection. Our 3-year graft survival rates were 70% for isolated intestinal transplantations and 41% for multivisceral transplantations (P = .02); graftectomy rate was 16%. These were 88% of grafts working properly with patients on regular diet with no need for parenteral nutrition. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the doses of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis, mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe acute chronic rejections.

Rejection episodes and 3-year graft survival under sirolimus and tacrolimus treatment after adult intestinal transplantation.

PURPOSE: Mammalian target of rapamycin (mTOR) inhibitors have been recently introduced in clinical practice after intestinal transplantation. We focused on Sirolimus (Rapamycin) to examine effects on rejection and graft survival following intestinal transplantation. PATIENTS AND METHODS: Twenty isolated intestinal recipients and 5 multivisceral patients (2 with liver) in our series were divided into 3 groups: patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who continued therapy longer than 3 months (n = 11); patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who received therapy less than 3 months because of side effects (n = 4); and a control group, who never received rapamycin (n = 10). RESULTS: During prolonged treatment combined with Tacrolimus (Prograf), both Sirolimus groups showed a decreased number of acute cellular rejections (P < .01). Cumulative 3-year graft and patient survival rates were 81% in the Sirolimus greater than 3 months group, 100% in the Sirolimus less than 3 months group, and 80% and 90% in the control group, respectively (P = .63 and P = .62). CONCLUSION: In our experience, the use of mTOR-inhibitors in combination with calcineurin-inhibitors seemed to be more effective than monotherapy to reduce the number of rejections. Side effects can limit its use as maintenance therapy.

Twenty-five consecutive isolated intestinal transplants in adult patients: a five-yr clinical experience.

PATIENTS AND METHODS: Between December 2000 and December 2005, 25 isolated intestinal transplants from cadaveric donors have been performed for short gut syndrome (short bowel syndrome, 52%), chronic intestinal pseudo-obstruction (24%), Gardner syndrome (16%), radiation enteritis (4%) and massive intestinal angiomatosis (4%). Indications for transplantation were: loss of venous access, recurrent sepsis due to central line infection, major electrolyte and fluid imbalance. Liver dysfunction was present in 13 cases. All patients were adult; median age was 36.3 yr and mean weight at transplantation 61.6 kg. All recipients were on life-threatening parenteral nutrition for a mean time of 23.7 months. Mean donor/recipient body weight ratio was 1.08. Rejection monitoring was accomplished by graft ileoendoscopies and intestinal biopsies through the temporary ileostomy. Our immunosuppressive regimen was based on induction therapy with three different protocols: daclizumab for induction, tacrolimus and steroids as maintenance therapy; alemtuzumab for induction and low-dose tacrolimus as maintenance; thymoglobulin for induction and maintenance based on low-dose tacrolimus. Closure of the abdomen at the end of transplantation represented a technical problem with several options performed: graft reduction, only skin closure, prothesic meshes, abdominal closure in two steps, cutaneous flaps and abdominal wall transplant in one case. RESULTS: The mean hospital stay was 37 days. The mean follow-up 27 months. Twenty patients are alive (80%) with two- and five-yr patient survival rate of 80% and 66%; mortality rate was 20% due to sepsis in all cases. Our two- and five-yr graft survival rate is 76% and 64%, graftectomy rate was 16%. Sixteen grafts are working properly, with no need of parenteral nutrition. We diagnosed 35 mild acute cellular rejection (ACRs), seven moderate ACRs and three severe ACRs (two needed graftectomy). We experienced two episodes of chronic rejection biopsy-proven. Rapamicine was added in case of renal failure or biopsy-proven intestinal rejection. Graft-vs.-host disease was not seen in our series while post-transplant lymphoproliferative disease in two cases. After discharge, the most common indication for medical support was dehydration. The abdominal wall transplant did not experience any rejection. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the amount of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis and the mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe ACR.

Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceral transplantation: A comparison of two different regimens on 29 recipients during the early post-operative period.

INTRODUCTION: Induction therapy has been recently adopted for intestinal transplant. PATIENTS AND METHODS: We compared during first 30 days post-transplantation 29 recipients, allocated in two groups, treated with Daclizumab (Zenapax) or Alemtuzumab (Campath-1H). RESULTS: During first month, 45% of Daclizumab recipients experienced six acute cellular rejections (ACRs) of mild degree, while 63% of them developed an infection requiring treatment. We found three acute cellular rejections in 17.6% of Alemtuzumab recipients, two with moderate degree; 64.7% of them required treatment for infection. DISCUSSION AND CONCLUSIONS: Graft and patient 3-years cumulative survival rate were not significantly different between groups. Alemtuzumab seems to offer a better immunosuppression during first month.

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.

Incidence, clinical significance, and outcome of vascular alterations in intestinal biopsies after isolated small bowel transplantation: a single-center experience.

BACKGROUND: Mild and moderate vascular alterations in intestinal biopsies after isolated small bowel transplantation (SBT) have uncertain clinical significance. METHODS: We retrospectively investigated the incidence, association with acute cellular rejection (ACR), treatment, and outcome of mild and moderate vascular changes in 15 adult SBTs performed between December 2000 and October 2003. The semiquantitative Ruiz score for vascular changes in intestinal mucosa was used. RESULTS: A total of 332 biopsies were analyzed. All patients had at least one sample showing mild or moderate vascular injury, which was globally found in 117 biopsies (35% of the total; 29% mild and 6% moderate). No cases of severe vascular injury were observed. First appearance of vascular alterations occurred 2 to 36 days after SBT (median: 6). Patients with vascular injury had a higher incidence of associated ACR than patients without this feature (16% vs 5%, P = .001). Patients with moderate vascular injury were also more likely to have moderate-to-severe ACR than patients showing no or mild vascular changes (14% vs 2%; P = .015). Treatment of rejection was more frequently administered with simultaneous diagnosis of ACR than in cases of isolated vascular alterations (84% vs 26%; P < .0001). Only one graft (7%) was lost due to severe ACR. DISCUSSION: Mild and moderate vascular changes are common findings in early post-SBT biopsies. They are frequently associated with ACR and parallel its severity. The clinical impact of mild or moderate vascular injury appears to be of little relevance.

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.

Combined liver-kidney transplantation: the experience of the University of Bologna and the case of preoperative positive cross-match.

Combined liver and kidney transplantation (CLKT) has been increasingly used in recent years: 13 of our 19 cases were performed in the last 2 years being 3.2% of our liver transplantation (LT) and kidney transplantation (KT) activity. Only three of them were not on hemodialysis and the scheduling of a CLKT meant being at the top of the waiting list. We accepted only ideal donors and had no case of liver and only one case of kidney delayed graft function. Two deaths occurred during the first postoperative month, due to acute respiratory distress syndrome and multiorgan failure, both in patients with adult polycystic disease who were in poor nutritional condition due to a late indication for CLKT. We had two late deaths, one due to a native kidney tumor at 7 years and one at 8 years due to alcoholic cirrhosis recurrence. The late survival of our patients was 77.3% with all surviving patients showing good liver and kidney function. We planned not to do the KT in the case of a positive preoperative cross-match; but the only positive case became negative 8 hours after LT when we performed the KT. The patient is well after 2 years. The liver does not always protect the kidney if there are preformed antibodies, but we should try every possible technique not to lose the possibility of doing both transplants, because in case of LT alone the patients loses his top position on the CLKT waiting list and often waits years for a kidney.

Intensive care complications in liver and multivisceral transplantation.

The complications concerning liver and intestinal transplant surgery have relevance for the field of intensive care because they share some characteristics with those following complex long-term surgery. Thus, in this article we shall try to describe complications that are specific to liver and multivisceral transplants. A review of the existing literature on this topic reveals a large number of studies dedicated to early as well as late surgical complications, and immunosuppressive treatment, while there are far fewer contributions describing complications exclusively concerning intensive care. We shall thus attempt to focus on certain aspects where, besides the literature data, we have personal experience. In particular we want to underline the implications of failure in the functional recovery of the graft; alterations in water, electrolyte, and glycemic balance; as well as neurological, respiratory, renal, nutritional, and infective complications.

Twenty-seven consecutive intestinal and multivisceral transplants in adult patients: a 4-year clinical experience.

Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P = .003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P = .01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.

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.

Laparoscopic Heller myotomy with or without partial fundoplication: a matter of debate.

AIM: To present our experience of laparoscopic Heller stretching myotomy followed by His angle reconstruction as surgical approach to esophageal achalasia. METHODS: Thirty-two patients underwent laparoscopic Heller myotomy; an anterior partial fundoplication in 17, and angle of His reconstruction in 15 cases represented the antireflux procedure of choice. RESULTS: There were no morbidity and mortality recorded in both anterior funduplication and angle of His reconstruction groups. No differences were detected in terms of recurrent dysphagia, p.o. reflux or medical therapy. CONCLUSION: To reduce the incidence of recurrent achalasia after laparoscopic Heller myotomy, we believe that His' angle reconstruction is a safe and effective alternative to the anterior fundoplication.

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.

Noninvasive preoperative evaluation of biliary anatomy in right-lobe living donors with mangafodipir trisodium-enhanced MR cholangiography.

BACKGROUND: Accurate preoperative radiologic imaging is essential to assess the vascular and biliary anatomy of right-lobe living donors and to ensure their safety. Volumetric magnetic resonance cholangiography (MRCP) using Mangafodipir trisodium (Mn-DPDP) contrast has been recently proposed to evaluate the biliary anatomy of living donor candidates. METHODS: During their preoperative evaluation, 18 right-lobe (RL) living donors underwent 3D Mn-DPDP-enhanced MRCP in addition to the standard thin- and thick-slab MRCP imaging. Immediately prior to hepatectomy all 18 RL donors underwent intraoperative cholangiography (IOC) via the cystic duct. We compared the efficacy of these different radiologic techniques to actual intraoperative IOC findings. RESULTS: Sixty-eight intrahepatic bile ducts were identified on IOC, 67(98.5%) by Mn-DPDP-enhanced 3D MRCP, 41 (60%) by thick-slab SSFSE imaging, and 35 (51%) by thin-slice SSFSE imaging. Mn-DPDP-enhanced 3D MRCP detected 100% (n = 5) of the anomalous origins of the right bile duct, and thick-slab MRCP detected 20% (n = 1) and thin-slab MRCP detected 0%. Anterior and posterior right intrahepatic bile ducts were identified by MnDPDP-enhanced 3D MRCP 100% of the time, by thick-slab SSFSE imaging 35% of the time, and by thin-slice SSFSE imaging only 12% of the time. CONCLUSIONS: Mn-DPDP-enhanced 3D MRCP imaging was highly sensitive and specific in identifying variants of the intrahepatic bile ducts. This technique should be included in the standard protocol of preoperative radiologic evaluation of RL living donor candidates.