Andrea Lauterio

Surgical treatment of hepatocellular cancer in the era of hepatic transplantation

BACKGROUND This study compares liver resection (LR) or transplantation (LTx) in an attempt to reevaluate the indications for treatment. STUDY DESIGN One hundred fifty-four LRs and 121 LTxs performed from 1985 to 1999 were considered. Survival and recurrence rate, together with age, gender, liver disease, Child-Pugh classification, alpha-fetoprotein (AFP), tumor capsule, vascular invasion, size, number of nodules, histologic grade, and pTNM were considered. Followup was completed in all cases (mean +/- SD = 3.2 +/- 2.9 years). RESULTS The 5- and 10-year actuarial survival rates were 61.7% and 59.8% in LTx and 46.9% and 28.0% in LR (p = 0.08). Recurrence-free survival was 85.9% and 85.9%, respectively, in LTx and 42.8% and 30.7% in LR (p < 0.0001). In both groups, size, capsule, AFP, vascular invasion, grade, pTNM, Child-Pugh classification, and age were all significantly related to survival and cancer recurrence. pTNM, AFP, Child-Pugh classification, and age, in LR, and capsule, AFP, and viral cirrhosis, in LTx, were significant independent variables in Coxs regression model for survival. Only AFP, vascular invasion, and grade were significant in both groups for recurrence. CONCLUSIONS LTx offers better recurrence freedom than LR, but longterm survival is not significantly different in the two series. A strict selection should be made to optimize graft allocation. Size and multifocality should not be considered absolute contraindications for LTx. AFP, vascular invasion, and grade are more likely to reflect the risk of recurrence of the disease. LR should be considered in patients who do not fulfill transplant criteria and also in some categories of patients with certain tumor characteristics (small resectable tumors in well-compensated cirrhosis).

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.

Biliary complications after living donor adult liver transplantation

The highest rate of complications characterizing the adult living donor liver transplantation (ALDLT) are due to biliary problems with a reported negative incidence of 22–64%. We performed 23 ALDLT grafting segments V–VIII without the middle hepatic vein from March 2001 to September 2005. Biliary anatomy was investigated using intraoperative cholangiography alone in the first five cases and magnetic resonance cholangiography in the remaining 18 cases. In 13 cases we found a single right biliary duct (56.5%) and in 10 we found multiple biliary ducts (43.7%). We performed single biliary anastomosis in 17 cases (73.91%) and double anastomosis in the remaining six (26%) cases. With a mean follow up of 644 days (8–1598 days), patient and graft survivals are 86.95% and 78.26%, respectively. The following biliary complications were observed: biliary leak from the cutting surface: three, anastomotic leak: two, late anastomotic strictures: five, early kinking of the choledochus: one. These 11 biliary complications (47.82%) occurred in eight patients (34.78%). Three of these patients developed two consecutive and different biliary complications. Biliary complications affected our series of ALDLT with a high percentage, but none of the grafts transplanted was lost because of biliary problems. Multiple biliary reconstructions are strongly related with a high risk of complication.

Should we still offer split‐liver transplantation for two adult recipients? A retrospective study of our experience

The role of split‐liver transplantation (SLT) for two adult recipients is still a matter of debate, and no agreement exists on indications, surgical techniques, and results. The aim of this study was to retrospectively analyze the outcome of our series of SLT. From May 1999 to December 2006, 16 patients underwent SLT at our unit. We used 9 full right grafts (segments 5‐8) and 7 full left grafts (segments 1‐4). The splitting procedure was always carried out in situ with a fully perfused liver. Postoperative complications were recorded in 8 (50%) patients: 5 (55%) in full right grafts and 3 (43%) in full left grafts. No one was retransplanted. After a median follow‐up of 55.82 months (range, 0.4‐91.2), 5 (31%) patients died, and the 1‐, 3‐, and 5‐year overall survival rate for patients and grafts was 69%. We considered as a control group for the global outcome 232 whole liver transplantations performed at our unit in the same period of time. Postoperative complications were recorded in 53 (23%) patients, and after a median follow‐up of 57.37 months (mean, 55.11; range, 1‐102.83), the 1‐, 3‐, and 5‐year overall patient survival was 87%, 82%, and 80%, respectively. In conclusion, SLT for two adult recipients is a technically demanding procedure that requires complex logistics and surgical teams experienced in both liver resection and transplantation. Although the reported rate of survival might be adequate for such a procedure, more efforts have to be made to improve the short‐term outcome, which is inadequate in our opinion. The true feasibility of SLT for two adults has to be considered as still under investigation. Liver Transpl 14:999–1006, 2008.

Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma progression before liver transplantation?

Background: To date the selection of the best candidates for liver transplantation (LT) owing to hepatocellular carcinoma (HCC) has been mainly based on tumor morphological characteristics (nodule diameter and number), which have resulted to be independent risk factors for short long-term survival and a high rate of tumor recurrence. Methods: The study cohort included 118 patients among the 166 with HCC transplanted at our unit from January 2000 to December 2007. Patients were classified according to response to locoregional treatments before LT: progressive Group A; complete Group B; partial Group C; stable Group D. Results: The 3-year and 5-year overall survival rates were 65.5% and 48.9% for Group A versus 84.8% and 74.6% for Group BCD (P=0.01). The 3-year and 5-year disease-free survival rates were 74% and 74% for Group A and 95.7% and 93% for Group BCD (P=0.007). HCC progression was the only independent risk factor according to Cox regression P=0.014 − odds ratio 4.4 (1.35−14.3). Conclusion: After aggressive HCC treatment before LT, imaging progression while on the waiting list was a strong predictor of high HCC recurrence rate also in patients who met the Milan criteria. Lack of imaging progression can contribute toward the selection of good transplant candidates for HCC together with the Milan criteria.

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.

Current status and perspectives in split liver transplantation

Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure.

Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia‐related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no‐touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393‐3268 IU/L). Patient and graft survival were both 100% after a mean follow‐up of 6.1 months (range, 3‐9 months). No cases of ischemic cholangiopathy occurred during the follow‐up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no‐touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166–173 2017 AASLD

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).

Adult Living Donor Liver Transplantation With Right Lobe Graft: The Venous Outflow Management in the Milan-Niguarda Experience

In right lobe living donor liver transplantation (ALDLT), reconstruction of middle hepatic vein (MHV) tributaries is often necessary to avoid severe graft congestion. From March 2001, we performed 36 right lobe ALDLT (segments 5, 6, 7, and 8) without MHV and one pediatric transplant (segments 2 and 3). In the presence of MHV tributaries larger than 5 mm, we intraoperatively evaluated the need for reconstruction. At a mean follow-up of 848 days (range=8-2412), 33/37 transplanted patients are alive with overall patient and graft survivals of 89.2% and 83.8%, respectively. Large MHV tributaries (>5 mm) were present in 10 cases, and inferior right hepatic veins (IRHV) draining segment 6 in 11 cases. In 10 cases, we performed an end-to-side anastomosis between the IRHV and the side of the recipient vena cava. In three cases, the MHV tributaries were end-to-end anastomosed to the stump of the recipient MHV. In all other cases, the vein tributaries were not reconstructed. A computed tomography scan performed from 1 to 3 months after surgery did not show any congested area in the liver parenchyma. In our experience, reconstruction of the MHV tributaries was not always necessary when graft-to-recipient weight ratio is >0.8. Pre- and intraoperative evaluation of the segmental branches of the hepatic vein is crucial to decide about reconstructing these collaterals. Anastomosis of V5 or V8 to the stump of the recipient MHV reduces the number of vascular anastomosis and maintains a physiological angle between these collaterals and the caval vein.