Liver Transplant for Metastatic Neuroendocrine Tumors: A Single-Center Experience in Hungary

Unresectable liver metastases of gastroenteropancreatic neuroendocrine tumors are an accepted indication for liver transplant. Patients undergoing liver transplant because of neuroendocrine tumor liver metastases have similar long-term survival compared with hepatocellular carcinoma; however, recurrence rates are reported to be higher.MethodsWe performed a retrospective analysis of medical records of patients who received transplants for neuroendocrine tumor liver metastases in the Department of Transplantation and Surgery of Semmelweis University between January 1995 and August 2018. The median follow-up period was 33 months.ResultsTen liver transplants have been performed because of neuroendocrine tumor liver metastases during the observed period. Recurrence occurred in 5 cases, and 3 patients died. Estimated 1- and 5-year patient survival rates after transplant were 89% and 71%, respectively. Estimated 1- and 5-year recurrence-free rates were 80% and 43%, respectively. Every patient whose primary tumor was of pancreatic origin or those recipients who had Ki67 index values in the explanted liver higher than 5% had disease recurrence.ConclusionPatient survival and recurrence rates after liver transplant were comparable with the results reported by other centers. In line with previous findings, primary pancreatic neuroendocrine tumors and higher Ki67 index values in the explanted livers were both associated with higher recurrence rates. We believe that an international registry would be helpful to better understand factors leading to tumor recurrence in these cases.     

Thromboelastography as a Predictor of Outcomes Following Liver Transplantation

Background

Thromboelastography (TEG) has been used perioperatively during liver transplantation (LT) to provide a real-time global hemostasis assessment for targeted blood product replacement. We aimed to analyze the relationship between post-LT TEG results and outcomes.

Liver Transplantation for Unresectable Neuroendocrine Tumor Liver Metastases

Background

Liver transplantation (LT) is performed in selected patients with neuroendocrine hepatic metastases. Survival benefit and the risk of tumor recurrence after LT, also exacerbated by immunosuppressive therapy, remain important clinical issues. Whether patients with particular types of neuroendocrine tumors (NET) benefit more than others is unclear.

Methods

Bibliographical searches were performed in PubMed for the terms “liver transplantation and neuroendocrine tumors,” “liver transplant and neuroendocrine tumors,” “liver transplantation and immunosuppressive therapy,” “tumor recurrence.”

Results

Promising results have been reported for LT for NET metastases with 5-year survival of up to 90 % in patients with well-differentiated gastroenteropancreatic NETs, but only few patients are free of tumor 5 years after LT. Better outcomes have been reported for gastrointestinal tumors than for pancreatic NETs for both survival and risk or recurrence after LT. Selection criteria for LT are limited and include the 2007 Milan Criteria and the 2012 European Neuroendocrine Tumor Society guidelines, including: well-differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease, primary tumor removed before transplantation, stable disease for at least 6 months before LT, and <50 % liver involvement.

Conclusions

LT might be considered in carefully selected patients. The risk of tumor recurrence remains a significant clinical problem after LT, but data focused on immunosuppression issue are lacking, and there are no currently approved strategies for prevention of recurrence or follow-up protocols. Further studies are needed to define universally accepted inclusion criteria, reliable predictors of better outcome, and optimal timing for LT.     

Survival Outcomes Following Liver Transplantation (SOFT) Score: A Novel Method to Predict Patient Survival Following Liver Transplantation

It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD‐predicted waitlist mortality. Univariate and multivariate analysis on 21 673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30 321 waitlisted candidates reevaluated the predictive ability of the Model for End‐Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3‐month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3‐month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures.     

Treatment of Hepatic Metastases from Gastroenteropancreatic Neuroendocrine Tumors: Role of Liver Transplantation

The role of liver transplantation in malignancy has been discussed, but controversially, over the past two decades. This is particularly true for hepatic metastases from neuroendocrine tumors, which have a wide variety of primary tumor localizations, morphologic types, functional activities, and clinical presentations. Despite generally slow tumor progression, the prognosis is often unpredictable. Total hepatectomy and liver replacement has been offered primarily to patients with nonresectable metastases and symptomatic disease. The results from retrospective single and multicentric analyses show that most liver recipients experience significant palliation despite tumor recurrence, and in some patients long-term cure can be achieved. The existing data emphasize the importance of proper selection and timing for this approach.     

The Long‐Term Benefit of Liver Transplantation for Hepatic Metastases From Neuroendocrine Tumors

Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty‐eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan‐NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long‐term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow‐up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time‐to‐progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4–23.0; p = 0.001). Adjusted transplant‐related survival benefit was 6.82 months (95% CI: 1.10–12.54; p = 0.019) and 38.43 months (95% CI: 21.41–55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long‐term outcome. Transplant‐related survival benefit increases over time and maximizes after 10 years.     

Role of Pretransplant Echocardiographic Evaluation in Predicting Outcomes Following Liver Transplantation

Maintenance of cardiac function is critical to the survival of patients with end‐stage liver disease after liver transplantation (LT). We sought to determine whether pre‐LT echocardiographic indices of right heart structure and function were independently predictive of morbidity and mortality post‐LT. We retrospectively studied 216 consecutive patients who underwent pre‐LT 2‐dimensional/Doppler echocardiography with subsequent LT from 2007 to 2010. A blinded reader analyzed multiple echocardiographic parameters, including right ventricular structure and function, pulmonary artery systolic pressure (PASP) and the presence and severity of tricuspid regurgitation (TR). On univariate analysis, Model of End‐Stage Liver Disease (MELD) score, PASP, presence of ≥mild TR, post–operative renal replacement therapy (RRT) and spontaneous bacterial peritonitis were found to be significant predictors of adverse outcomes. On multivariate analysis, only ≥mild TR was found to predict both patient mortality (p = 0.0024, HR = 3.91, 95% CI: 1.62–9.44) and graft failure (p = 0.0010, HR = 3.70, 95% CI: 1.70–8.06). PASP and MELD correlated with post‐LT intensive care unit length of stay (LOS) and, along with hemodialysis, were associated with hospital LOS and time on ventilator. In conclusion, pre‐LT echocardiographic assessments of the right heart may be useful in predicting post‐LT morbidity and mortality and guiding the selection of appropriate LT candidates.     

Mixed Hepatocellular Cholangiocarcinoma: A Review of Long-Term Outcomes Following Liver Transplantation

Introduction

Mixed hepatocellular cholangiocarcinoma (HCC-CC) represents a rare hepatic tumor, which demonstrates histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). HCC-CC can be an unexpected finding in patients undergoing liver transplantation (LT) for HCC. The objective of our review was to review and evaluate long-term outcomes in patients undergoing LT for mixed HCC-CC.

Liver Transplantation for Primary or Metastatic Sarcoma to the Liver

Sarcoma is generally a rare disease in the US, with poor survival in patients with both primary angiosarcoma and metastatic disease from sarcoma and GIST. In order to determine if liver transplantation for sarcoma is a realistic option, we examined records of all patients in the US component of the Israel Penn International Transplant Tumor Registry were reviewed. Those patients with liver failure from primary or metastatic liver sarcoma were evaluated. Patient outcome analysis was then performed. Patient and tumor demographics were reviewed as well as patient survival after transplantation. 19 patients are identified having received liver transplantation after treatment for sarcoma of the liver, 6 patients with primary hepatic sarcoma and 13 patients with metastatic sarcoma of the liver. Recurrence was almost universal in 18 of 19 patients (95%) after a median interval of 6 months. Survival for the group as a whole was 47% for 1-year, 15% for 3-years and 5% for 5-years. Given the early recurrence of tumor and meager 1-year survival outcome, liver transplantation is a poor therapeutic choice for patients with either primary or metastatic liver sarcoma, including high-grade leiomyosarcoma (GIST) regardless of primary site or primary therapy.     

Outcomes of Renal Transplantation Following Bone Marrow Transplantation

This single center retrospective study was undertaken to determine the outcome of kidney transplantation (KT) after bone marrow transplantation (BMT) and also to determine the need for immunosuppressive therapy after KT when the BMT marrow donor is the KT donor. Kidney transplantation was performed in 10 patients with BMT nephropathy (BMTN). In six patients, the KT donor was the BMT donor; these individuals were given no long-term immunosuppression. Four other patients received KT from donors who were not the marrow donor (two living donors, two cadaveric donors). After median follow up of 34 months, no patient had an episode of acute rejection. All graft losses (n = 4) resulted from patient death. Three were because of infectious processes, including two infectious deaths in patients not on immunosuppression. Median estimated actuarial patient and graft survival (Kaplan-Meier) was 105 months. We conclude that patients with BMTN who receive KT from their marrow donor do not require immunosuppression. Whether immunosuppressive therapy is given or not, outcome appears to be determined largely by BMT-related immune dysfunction.     

Synchronous Resection of Primary and Liver Metastases for Neuroendocrine Tumors

Background

Surgical approach is an accepted approach for metastatic neuroendocrine tumors (NET), but the safety and effectiveness of synchronous liver metastases resection with primary and/or locally recurrent NET is unclear.

Methods

From 1992 to 2009, a total of 36 patients underwent synchronous resection of primary NET or local recurrence and liver metastases. Patients and tumor characteristics, surgical procedures, and postoperative and long-term outcome were reviewed.

Results

Primary lesions were solitary in 28 patients (80?%), with a median size of 25?mm. Liver metastases were multiple in 32 cases (89?%), with a bilobar distribution in 29 patients (81?%) and a median size of 62?mm. Resections included gastroduodenal (n?=?5), ileocolonic (n?=?18), pancreatic resection (n?=?13), and major hepatectomy (n?=?15). Resections were R0, R1, and R2 in 13, 11, and 12 cases, respectively, and tumors were classified as G1 in 20 (56?%) and G2 in 15 (42?%). There was 1 postoperative death after a Whipple/right trisectionectomy, and postoperative complication occurred in 16 patients (44?%). With a median follow-up of 56?months, 31 patients (89?%) experienced recurrence, which was confined to the liver in 90?%. Reduction of disease to liver only allowed subsequent liver-directed therapy, such as arterial embolization or percutaneous ablation, in 25 patients (71?%). Five-year symptom-free survival and overall survival were 60?%, and 69?%, respectively.

Conclusions

In highly selected patients, an initial surgical approach combining simultaneous resection of liver metastases and primary/recurrent tumors can be performed with low mortality. Most patients develop liver-confined recurrence, which is usually amenable to ablative therapies that offer ongoing disease and symptom control.     

应用肝移植治疗神经内分泌肿瘤肝转移的新进展

目的 介绍肝移植治疗神经内分泌肿瘤肝转移的进展.方法 收集国内、外近年来有关肝移植治疗神经内分泌肿瘤肝转移的文献并进行分析和综述.结果 神经内分泌肿瘤进展缓慢,对于不能切除的肝脏神经内分泌转移瘤,经过严格的临床和病理组织学评估后实行肝移植,症状能够有效地缓解甚至可能治愈.结论 选择合适的患者,肝移植治疗神经内分泌肿瘤肝转移效果良好.     

Long-Term Outcomes Following Liver Transplantation for Hepatic Hemangioendothelioma: The UNOS Experience from 1987 to 2005

Introduction Hepatic hemangioendothelioma (HEH) is a vascular neoplasm with intermediate malignant potential. Outcomes after liver transplantation have only been reported as small, single-institution experiences. The purpose of this study was to evaluate patient and allograft survivals after liver transplantation in a large, multi-institutional cohort of patients with HEH. Methods Using the United Network for Organ Sharing (UNOS) database, we identified 110 patients with a diagnosis of HEH who underwent 126 transplants between 1987 and 2005. Patient and allograft survivals were calculated using Kaplan–Meier survival curves. Log rank tests were used to determine the influence of study variables on outcomes. Results Of the 110 transplanted patients, 75 patients (68%) were female, 80 patients (73%) were Caucasian, and the median age was 36 years old (23% < 4 y.o., 71% > 18 y.o.). The 30-day posttransplant mortality rate was 2.4%. At a median patient follow-up interval of 24 months, 1- and 5-year patient and allograft survivals were 80% and 64%, and 70% and 55%, respectively. Pretransplant medical status, but not age, was found to statistically correlate with patient survival. Conclusion These data indicate that survivals after transplantation for HEH are favorable. Given the propensity for recurrence after resection, these data support consideration of liver transplantation for all patients with significant intrahepatic tumor burden. Presented at the 7th Annual American Hepato-Pancreato-Biliary Association Meeting, April 20, 2007, Las Vegas, NV     

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors

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Predictors of Long-Term Survival After Liver Transplantation for Metastatic Endocrine Tumors: An 85-Case French Multicentric Report

Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver ≥120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven.
Postoperative in-hospital mortality was 14%. Overall 5-year survival was 47%. Independent factors of poor prognosis according to multivariate analysis included UAE (relative risk (RR): 3.72), primary tumor in duodenum or pancreas (RR: 2.94) and hepatomegaly (RR: 2.63). After exclusion of cases involving concomitant UAE, the other two factors were combined into a risk model. Five-year survival rate was 12% for the 23 patients presenting both unfavorable prognostic factors versus 68% for the 55 patients presenting one or neither factor (p < 10⁻⁷).
LTx can benefit selected patients with nonresectable MET. Patients presenting duodeno-pancreatic MET in association with hepatomegaly are poor indications for LTx.     

Surgical Treatment of Primary Neuroendocrine Tumors of the Liver

Primary neuroendocrine tumor (NET) of the liver is a very rare neoplasm, requiring strict exclusion of possible extrahepatic primary sites for its diagnosis. We have analyzed our clinical experience of eight patients with hepatic primary NET. From January 1997 to December 2006, eight patients with a mean age of 50.4 ± 9.5 years underwent liver resection for primary hepatic NET. Seven patients underwent preoperative liver biopsies, which correctly diagnosed NET in four. Of the eight patients, six underwent R0 and two underwent R1 resection. Diagnosis of hepatic primary NET was confirmed immunohistochemically and by the absence of extrahepatic primary sites. All tumors were single lesions, of mean size 8.6 ± 5.7 cm, and all showed positive staining for synaptophysin and chromogranin. During a mean follow-up of 34.0 ± 39.7 months, three patients died of multiple liver metastases after tumor recurrence, whereas the other five remain alive to date, making the 5-year recurrence rate 40% and the 5-year survival rate 56.3%. Univariate analysis showed that Ki67 proliferative index was a risk factor for tumor recurrence. In conclusion, although primary hepatic NET is very rare, it should be distinguished from other liver neoplasms. The mainstay of treatment is curative liver resection.     

Tracheostomy Following Lung Transplantation Predictors and Outcomes

The effect of tracheostomy on patients receiving lung transplantation is unknown. We reviewed our experience by performing a retrospective analysis on all lung transplant recipients at our institution. Patients were assigned to each study group based on whether or not they received a tracheostomy in the acute postoperative period. One hundred and fourteen lung transplants were performed, and 16 of those patients received a tracheostomy. In the tracheostomy group, more patients had undergone bilateral-lung transplantation (81% vs. 34%, p = 0.001), more required cardiopulmonary bypass (75% vs. 38%, p = 0.005), more acquired postoperative pneumonia (88% vs. 30%, p < 0.001), had greater reperfusion injury at 48 h (PaO2/FiO2 of 233 vs. 345, p = 0.047), had longer initial periods on the ventilator (21 +/- 7 vs. 2 +/- 0.5 days, p < 0.001), more required re-intubation (56% vs. 18%, p = 0.001), spent longer times in the intensive care unit (30 +/- 7 vs. 5.5 +/- 0.9 days, p < 0.001), and had longer lengths of stay (67 +/- 10 vs. 22 +/- 2 days, p < 0.001). Despite these differences between the two groups, a significant difference in survival at 180 days (75 vs. 81%) did not exist (p = 0.89). Although tracheostomy is more likely in sicker patients, it is not associated with poor long-term outcomes.