Single Hepatocellular Carcinoma approached by curative-intent treatment: A propensity score analysis comparing radiofrequency ablation and liver resection.

INTRODUCTION: Patients with a single small Hepatocellular Carcinoma (HCC) may be definitively treated by Radiofrequency ablation (RFA) with a very low rate of peri-operative morbidity. However, results are still controversial comparing RFA to Liver Resection (LR). METHODS: All consecutive patients treated by RFA or LR for a single untreated small HCC on liver cirrhosis between January 2006-December 2016 were enrolled. Patients were matched 1:1 basing on: age, MELD-score, platelet count, nodule's diameter, HCV status, α-fetoprotein level, and Albumin-Bilirubin score. First analysis compered LR to RFA. Second analysis compared Laparoscopic LR (LLR) to RFA. RESULTS: Of 484 patients with single small HCC, 91 patients were selected for each group after a 1:1 propensity score matching (PS-M). The 5-years OS was 70% and 60% respectively for LR and RFA group (P = 0.666). The 5-year RFS was 36% and 21% respectively for LR and RFA group (P < 0.001). Patients treated by LR had a significantly longer hospital stay and higher complications rate. Comparing 50 cases of LLR and 50 of RFA, the 5-years OS was 79% and 56% respectively for LLR and RFA group (P = 0.22). The 5-year RFS was 54% and 19% respectively for LR and RFA group (P < 0.001). Post-operative complications were not significantly different. CONCLUSIONS: LLR confers similar peri-operative complications rate compared to RFA. LLR should be considered as a first-line approach for the treatment of a single small HCC as it combines the effectiveness of open LR and the safety profile of RFA.

Human immunodeficiency virus and liver transplantation: our point of view.

INTRODUCTION: Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of HIV patients with a consequent increase in the number of HIV patients affected by end-stage liver disease (ESLD). Between June 2003 and October 2006, 10 HIV-positive patients underwent liver transplantations in our center. METHODS: All patients were treated with HAART before transplantation; treatment was interrupted on transplantation day and was restarted once the patients' conditions stabilized. Five patients were hepatitis C virus (HCV)-positive, 3 were hepatitis B virus (HBV)-positive, and 2 were HBV-HCV coinfected. HIV viral load before transplantation was <50 copies/mL in all cases. CD4+ cell count before transplantation ranged between 144 and 530 c/microL. Immunosuppression was based on Cyclosporine (CyA) and steroid weaning for 8 patients, and on Tacrolimus and steroid weaning for 2 patients. RESULTS: Five patients were cytomegalovirus (CMV)-positive pp65 antigenemia posttransplantation, and 1 patient was EBV-positive; 2 patients had a coinfection with HHV6. Four patients suffered from a cholestatic HCV recurrent hepatitis treated with antiviral therapy (peginterferon and Ribavirin). Three patients died after transplantation. DISCUSSION: The outcome of liver transplantation in HIV patients was influenced by infections (HCV, CMV, and EBV) and Kaposi's Sarcoma. HCV recurrence was more aggressive, showing a faster progression in this patient population. Drug interaction between HAART and immunosuppressants occurs; longer follow-up and better experience may improve the management of these drug interactions.

Temporary porto-caval shunt utility during orthotopic liver transplantation.

INTRODUCTION: In liver transplantation (OLT) a porto-caval shunt is a well-defined technique practiced by many surgeons in several centers. METHODS: We considered 186 cadaveric OLT patients who underwent a cavo-cavostomy-type reconstruction; they were divided into two groups: those in whom we performed a porto-caval shunt (group A) and those in whose we did not (group B). We evaluated several variables: warm and total ischemia time, intraoperative blood and fresh frozen plasma transfusions, crystalloid and colloid requirements, blood loss, operative duration, hemodynamic intraoperative changes and diuresis, length of hospital stay, and creatinine values at days 1 and 2, and at discharge day. RESULTS: Total and warm ischemic time differed significantly between the two groups. Infusion of blood, fresh frozen plasma, colloid, and crystalloid did not significantly differ. Blood loss was lower, and intraoperative diuresis was not significantly increased in group A subjects. Postoperative hospitalizations were 16.5 and 17.8 days and operative times, 504 and 611 minutes in the two groups. Both cardiac index and ejection fraction values during the anhepatic phase were significantly greater among group A than group B patients. PAD at the two phases was greater in group B. The PAS was significantly different only at reperfusion time. Creatinine values were significantly different at discharge. Better survival was shown for group A patients over group B subjects. CONCLUSION: The results presented herein confirmed that a porto-caval shunt during OLT was a safe, useful expedient contributing to an improved hemodynamic status and a better time distribution in the various phases of liver transplantation.

Sirolimus monotherapy in liver transplantation.

INTRODUCTION: Since 1999, a new immunosuppressive drug was administered to renal transplant patients. The SRL molecule acts by blocking post-receptor signal transduction of interleukin-2 (IL-2) interacting with a family of intracellular binding proteins termed immunophilins FKBPs. Among these FKBPs, FK506 12-kd binding protein is the most relevant. SRL is an immunosuppressive drug. Therefore it can inhibit the immune system; at the same time the drug is not nephrotoxic, neurotoxic, and without diabetogenic effects. METHODS: Among 285 patients who underwent liver transplantation, 27 took Sirolimus as monotherapy. Immunosuppressive treatment upto cyclosporine (CsA) or tacrolimus (FK) associated with steroids (methylprednisolone) and mycophenolate Mofetil (MMF) was initiated among subjects with pre-transplant renal failure. SRL was administered as monotherapy for patients who developed nephrotoxicity, or neurotoxicity, or diabetes. Moreover, patients affected by multifocal HCC who did not meet the Milan criteria or patients who developed Kaposi's Sarcoma were prescribed SRL monotherapy. RESULTS: Nephrotoxicity occurred in 14 patients with mean serum creatinine level 2.2 mg/dl. Eleven patients with real failure showed significant improvements after a mean period of 28 days of SRL monotherapy (range: 6-45 days). The mean creatinine serum level after treatment with SRL monotherapy was 1.0 mg/dl (range: 0.7-1.2 mg/dl). Neurotoxicity occurred in 4 patients with tremor, confusion, and agitation. Each patient had complete improvement of symptoms after a few days of Sirolimus monotherapy. Among Three patients who developed Kaposi's Sarcoma, two underwent remission. One patient had diabetes due to calcineurin inhibitors, and one showed arterial hypertension not treatable with drugs. After the switch, we treated these patients with medications. Another important indication was HCC not meeting the Milan criteria. CONCLUSION: SRL monotherapy may be used to manage complication of calcineurin inhibitors or Kaposi's Sarcoma.

Robot-Assisted Harvesting of Kidneys for Transplantation and Global Complications for the Donor.

INTRODUCTION: Robot-assisted kidney harvesting from living donors is feasible and safe. We report the results of a mono-centric experience relative to 98 consecutive robotic nephrectomies with emphasis on global donor complications. MATERIALS AND METHODS: This is a retrospective cohort study. Donors underwent robot-assisted kidney harvesting. The preferred kidney was the left one even in the presence of vascular anomalies. In the first cases we used a robotic hand-assisted technique, then the totally robotic technique, and finally the modified totally robot-assisted technique. Postoperative complications were ranked according to the five-grade Clavien-Dindo classification. RESULTS: Between November 2009 and November 2016, 98 living donors underwent nephrectomy. We experienced 14 complications. The 3 intraoperative ones (3.06%) were 1 pneumothorax and 2 acute bleedings, 1 of them requiring transfusion. The 11 postoperative complications (11.22%) were as follows: 5 wound seromas, 1 rhabdomyolisis (Clavien I), 1 paretic ileum, 1 anemia requiring transfusion, 1 hypertensive crisis (Clavien II), and 2 chylus collections drained by interventional radiologists (Clavien III). Transfusion rate was 2.1%; conversions, reoperations, and mortality were nil. No statistically significant difference was observed between the patients with complications and without in terms of gender, age, anatomical anomalies, body mass index (BMI), and learning curve. We observed a longer global operation length of time in patients with complications. CONCLUSION: Robotic assistance results in shorter and simpler learning curves for the harvesting of kidneys from living donors. It enables an easier and more efficient management of possible intraoperative complications. The rate of postoperative complications is comparable with the rate of complications encountered in traditional laparoscopic series with high numbers of harvestings.

Hepatic hilum management in 250 liver-multivisceral procurements.

An accurate in vivo preparation of the hepatic hilum is a fundamental prerequisite for a successful multiorgan transplantation. Our preferred technique in this surgical setting is in vivo procurement in the heart-beating donor. This technique allows an effective exposition of the hilum structures and recognition of anatomical vascular variants, particularly those of the hepatic artery. Also, the cold ischemia time is drastically reduced, and the back-table preparation is left to a minimum. In this article we show the results of a consecutive series of 250 procurements.

Do Older Liver Grafts Have Worse Survival? The Niguarda Experience.

BACKGROUND: Elderly donor livers are thought to be marginal graft. In the present study, we aimed to identify an age threshold to consider a graft as elderly to identify the trend (if any) of the donor age in our series and to identify an efficient allocation criteria for elderly grafts. METHODS: We reviewed in a retrospective manner our series of 1520 liver transplants, comparing graft survival under and over a certain age. On the basis of the results of this analysis, we identified a threshold of 70 years to define a graft as old. The donor age trend analysis showed an increasing rate of transplants from elderly donors. RESULTS: To identify efficient allocation criteria for elderly graft, we stratified the series by the disease of the recipient: 556 patients underwent transplants for hepatocellular carcinoma (HCC+ group) and 964 for other diseases (HCC- group). Two hundred twenty-one patients of 556 of the HCC+ group were hepatitis c virus (HCV) negative (HCC+/HCV- group), and 312 of 964 of the HCC- group were HCV positive (HCC-/HCV+). The survival analysis showed no significant differences in comparing the outcome for elderly and young grafts in the HCC+ (P = .135) and HCC- (P = .055) groups. CONCLUSIONS: When comparing the survival of old and young livers in the HCC+/HCV- group, the elderly livers appear to have a better outcome (P = .05); on the other hand, the same analysis in the HCC-/HCV+ group shows a worse outcome for old-aged grafts (P = .026). Therefore, the present study suggests that elderly livers should be allocated to hepatocellular carcinoma (HCC) patients and should be avoided in HCV+ recipients.

Split-liver full-left full-right: proposal for an operative protocol.

INTRODUCTION: Worldwide, organ shortage is a major limiting factor to transplantations. One possible way to face graft scarcity is splitting full livers into hemilivers; this procedure would allow transplantation in 2 adult recipients with the use of a single organ from a deceased donor. OBJECTIVE: The goal of this study was to describe an adult-to-adult split liver operative protocol and share it between centers interested in exploring this procedure. MATERIALS AND METHODS: A literature review was first conducted to elaborate on the present protocol; second, selection criteria for suitable deceased donors were identified. The technical aspects of performing the procurement were also analyzed; finally, the recipient selection criteria and the transplantation criteria were determined. RESULTS: The donor characteristics should be consistent with the following: age≤55 years; weight≥70 kg; body mass index<28 kg/m2; intensive care unit stay<7 days; sodium level<160 mEq/L if the intensive care unit stay is >2 days; maximum transaminase value 3 times normal; hemodynamic stability; negative for hepatitis B surface antigen, hepatitis C virus, and human immunodeficiency virus; macrosteatosis<20%; macroscopic adequacy; and absence of anatomic anomalies requiring complex reconstruction. The procurement hospital should provide the preoperative computed tomography scan, liver dissector, and the intraoperative ultrasound. Indication for in situ or ex situ splitting depends on the hepatic vein outflow anatomy. Graft-to-recipient weight ratio should be ≥1%, and the graft-to-recipient spleen size ratio should be ≥0.6. United Network for Organ Sharing status 1 and 2A recipients are excluded, as are patients with transjugular intrahepatic portosystemic shunts. Hemiliver transplants are performed as in living-donor liver transplantation, and portal hyperflow is corrected by splenic artery ligation, splenectomy, and portal infusion of vasoactive drugs. CONCLUSIONS: The present protocol was proposed to test the validity of the full-left full-right split liver procedure. A retrospective analysis found that 130 transplantations were suitable for this procedure according to the present protocol in the period January 1, 2008, through December 31, 2011 (65 donors). We believe that these numbers could be greatly increased once this procedure is proven feasible and safe within the proposed criteria.

Colorectal liver metastases: hepatic pedicle clamping during hepatectomy reduces the incidence of tumor recurrence in selected patients. Case-matched analysis.

BACKGROUND: Hepatic pedicle clamping (HPC) during Liver Resection (LR) is a vascular procedure designed to prevent bleeding from the liver during hepatectomy. Outgrowth of pre-existing colorectal micrometastases may occur 5-6 times faster in occluded liver lobes than in non-occluded lobes. We conducted a case-matched analysis at our Institution to assess the effects of HPC on overall and recurrence-free survival in highly selected patients, who underwent LR due to Colorectal liver metastases (CLM). MATERIALS AND METHODS: From January 2002 to December 2010, 120 patients operated for CLM were included into this case-matched study. Patients were allocated to two groups: Group-A patients who underwent HPC during LR; Group-B patients who underwent LR without HPC. RESULTS: HPC during liver resection was associated with better overall patient 5-year survival (47.2% in Group-A and 32.1% in Group-B) (P-value = 0.06), and significantly better 5-year recurrence-free survival (49.9% in Group-A vs 18.3% in Group-B) (P-value = 0.010) The Cox regression model identified the following risk factors for worse prognosis in terms of shorter recurrence-free survival and higher incidence of tumor recurrence: no HPC (Group-B) (P-value = 0.032) and positive lymph nodes at the time of LR (P-value = 0.018). CONCLUSION: Lack of HPC in selected patients who underwent LR for CLM results to be a strong independent risk factor for higher patient exposure to tumor recurrence. We suggest that hepatic hilum clamping should be seriously taken into consideration in this patient setting. MINI-ABSTRACT: A case-matched study was performed in 120 patients undergoing liver resection due to colorectal liver metastases, comparing patients who received intermittent hepatic pedicle clamping (HPC) with those who did not. The 5-year overall survival rate was similar, but the 5-year recurrence-free rate was significantly higher with no HPC (p = 0.012).

Initial experience with robot-assisted nephrectomy for living-donor kidney transplantation: feasibility and technical notes.

BACKGROUND: Robot-assisted surgery provide endowrist instruments and 3-dimensional visualization of the operative field that are improvements over traditional laparoscopy. The few research studies published so far have demonstrated that living-donor nephrectomy using the robot-assisted technique is safe and feasible, providing advantages for patients. METHODS: Since November 2009, we performed 20 robot-assisted living-donor nephrectomies. Eight patients underwent hand-assisted robotic nephrectomy, whereas 20, totally robotic nephrectomy. RESULTS: Median intraoperative bleeding was 174 mL (range, 10-750) but no patient needed intraoperative transfusion with blood cells. The median warm ischemia time was 3.16 minutes (range, 0.30-6.5). there was no case of conversion to an open procedure. The median operative time was 311 minutes (range, 85-530); the median console time was 160 minutes (range, 135-220). CONCLUSION: Robot-assisted living-donor kidney recovery was a safe and effective procedure. The totally robotic recovery is an evolving technique. The prospect of robotic staplers, endowrist ligature, and robotic single port may further increase these advantages.

Living-donor liver transplantation: donor selection criteria and postoperative outcomes. A single-center experience with a 10-year follow-up.

BACKGROUND: Donor safety must be considered to be a priority in live-donor liver transplantation (LDLT). The aim of this study was to evaluate these outcomes with special attention to surgical complications and their treatment. METHODS: From March 2001 to March 2012, 80 live donors underwent right hepatectomy (5-8 segments). The middle hepatic vein was always left in the donor. Our retrospective study analyzed surgical outcomes and complications according to the Clavien classification modified for live donors. RESULTS: With a median follow up of 63.2 ± 12.6 months, the mortality was 0%. Two donors experienced intraoperative complications, but all of them had complete recovery there after. Among the 22 complications in 17 donors (21.2%), 7 (8.7%) were major complications (Clavien grade 2b) but only 2 donors required surgical treatment. CONCLUSIONS: LDLT is a safe and feasible modality to alleviate the cadaveric donor shortage. The efficacy of this procedure is similar to that with deceased donors.

Hepatocellular carcinoma in unrelated viral cirrhosis: long-term results after liver transplantation.

INTRODUCTION: Chronic viral hepatitis is considered to be the most significant risk factor for development of hepatocellular carcinoma (HCC). Nevertheless, about 5%-15% of HCC occur in noncirrhotic or virus-unrelated cirrhotic patients. The natural history of HCC in terms of incidence, clinical features, and tumor progression differs according to the underlying cancerogenic factors and differences in hepatocarcinogenetic pathways. Little is know about the relationship between HCC outcomes after liver transplantation (OLT) and the primary liver disease. We retrospectively analyzed the outcomes of patients transplanted due to HCC in settings of either virus-related or virus-unrelated cirrhosis. PATIENTS AND METHODS: From January 2000 to December 2007, 179 patients underwent OLT due to HCC: 157 (87.8%) affected by virus-related (group A) and 22 (12.2%) virus-unrelated cirrhosis (group B). We analyzed patient characteristics including demographics, tumor features, downstaging treatments, and recurrences. RESULTS: At a mean follow-up of 41.2 months, the 3- and 5-year overall long-term survivals between group A versus group B were 81% versus 75% and 85% versus 78.4% respectively (P = NS). The 3- and 5-year disease-free survivals between group A versus group B were 90.8% versus 89.6% and 85.6% versus 85.6%, respectively (P = NS). After OLT, HCC recurrences occurred in 14 group A (14/157, 8.9%) and 4 patients (4/22, 18.1%) group B subjects. DISCUSSION: Our data demonstrated that after OLT, HCC outcomes were not different between patients with virus-related or -unrelated cirrhosis. The direct oncogenetic role played by hepatitis B and C appear to not be associated with a greater risk to develop HCC recurrence.

Living donor liver transplantation for hepatocellular carcinoma: long-term results compared with deceased donor liver transplantation.

OBJECTIVE: Living donor liver transplantation (LDLT) may represent a valid therapeutic option allowing several advantages for patients affected by hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). However, some reports in the literature have demonstrated worse long-term and disease-free survivals among patients treated by LDLT than deceased donor liver transplantation (DDLT) for HCC. Herein we have reported our long-term results comparing LDLT with DDLT for HCC. PATIENTS AND METHODS: Among 179 patients who underwent OLT from January 2000 to December 2007, 25 (13.9%) received LDLT with HCC 154 (86.1%) received DDLT. Patients were selected based on the Milan criteria. Transarterial chemoembolization, radiofrequency ablation, percutaneous alcoholization, or liver resection was applied as a downstaging procedure while on the waiting list. Patients with stage II HCC were proposed for LDLT. RESULTS: The overall 3- and 5-year survival rates were 77.3% and 68.7% versus 82.8% and 76.7% for LDLT and DDLT recipients, respectively, with no significant difference by the log-rank test. Moreover, the 3- and 5-year recurrence-free survival rates were 95.5% and 95.5% (LDLT) versus 90.5% and 89.4% (DDLT; P = NS). CONCLUSIONS: LDLT guarantees the same long-term results as DDLT where there are analogous selection criteria for candidates. The Milan criteria remain a valid tool to select candidates for LDLT to achieve optimal long-term results.

Liver adenomatosis: a rare indication for living donor liver transplantation.

Liver adenomatosis (LA) is a rare benign disease of the liver with unclear pathogenesis, which is characterized by multiple hepatic adenomas. The management of LA remains controversial. Herein we have reported a case of LA treated by living donor liver transplantation (LDLT). A 48-year-old woman developed multiple liver adenomas. In view of the sizes and localizations of the lesions, the patient underwent right hepatic resection and segment II nodulectomy. Thirty-four months later, she developed recurrence of multiple hepatic adenomas and 2 nodules were highly suspect for hepatocellular carcinoma. Re-resection was not indicated due to the whole liver being involved with adenomas. The patient underwent LDLT. At 45 months thereafter she is alive and disease-free. In conclusion, LDLT is indicated in cases of nonresectability; it may offer optimal results in view of the absence of portal hypertension and the elimination of waiting list time.

Immunosuppressive switch to sirolimus in renal dysfunction after liver transplantation.

OBJECTIVE: Nephrotoxicity is a serious adverse effect after liver transplantation often related to calcineurin inhibitors (CNI) with a incidence of 18.1% at 5 years. Sirolimus (SRL) is a new immunosuppressive drug that was introduced into solid organ transplant management in 1999. Herein we have performed a retrospective review of patients who developed renal insufficiency owing to CNI therapy after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Thirty-one patients were switched to SRL monotherapy because of nephrotoxicity as evidenced by serum creatinine levels (SCr) > 1.8 mg/dL and estimated glomerular filtration rates (eGFR) < 45 mL/min/1.73 m(2). The dosage was adjusted to achieve trough levels between 8 and 10 ng/mL. RESULTS: The patients were followed for a mean of 52 months (range 2-88 months) after OLT. Mean follow-up after the switch was 27.5 months (range, 2-71.2 months). Immunosuppression was switched after a mean of 35.2 months (range, 0.2-43.4 months). Renal function was significantly improved, as shown by the improved SCr, urea, and eGFR after the switch. CONCLUSIONS: CNIs may be associated with significant nephrotoxicity and chronic kidney damage. Patients who develop renal dysfunction after OLT may be successfully treated by an early switch from CNIs to SRL, stopping the progression toward chronic renal damage and preserving allograft survival.

Hepatocellular carcinoma in HIV patients treated by liver transplantation.

INTRODUCTION: Several reports have shown the effectiveness of liver transplantation (LT) as a therapeutic option in HIV-patients affected by end-stage liver disease. HCC on cirrhosis is another major indication for LT. However, no reports, to our knowledge, have been published as yet addressing the important questions of indications and outcome of LT in HIV-patients with HCC, mainly because of concerns regarding a more aggressive course of HCC with respect to HCC seen in HIV-negative individuals. METHODS: The aim of this report is to focus on indications, preliminary results and complications of LT in a group of 7 HIV-patients who underwent LT at our department for HCC on cirrhosis. RESULTS: Indications to listing HIV-patients were HCC using the internationally accepted Milan criteria. All patients were HBV-and/or HCV-infected. The mean CD4+ cell-count was 249 (range 144-353), and the HIV-RNA load was undetectable in all but one case. After a mean follow-up period of 232days (range 33-774), no recurrence of HCC was seen; one patient died. CONCLUSION: Characteristics of the study protocol, the patients, virological and immunological features, tumor stage and pre-transplantation treatment, complications and survival are herein described in an effort to provide new insights into methodology for an aggressive management of HCC in HIV patients, and possibly give a greater chance of cure.