Hepatocellular carcinoma tumour burden score to stratify prognosis after resection.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. METHODS: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. RESULTS: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). CONCLUSION: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

ANTECEDENTES: Aunque el sistema de estadificación del Barcelona Clinic Liver Cancer (BCLC) ha sido adoptado en gran medida en la práctica clínica, estudios recientes han enfatizado la necesidad de un mayor refinamiento y subclasificación del sistema BCLC. MÉTODOS: Los pacientes con carcinoma hepatocelular (hepatocellular cancer, HCC) BCLC-0, A y B que se sometieron a una hepatectomía con intención curativa entre 2000 y 2017 fueron identificados utilizando una base de datos multi-institucional. Se calculó la puntuación de carga tumoral (tumour burden score, TBS) y se examinó la supervivencia global (overall survival, OS) en relación con la TBS y los estadios BCLC. RESULTADOS: En la serie de 1.053 pacientes, 63 (6%) tenían HCC BCLC-0, 826 (78,4%) HCC BCLC-A y 164 (15,6%) HCC BCLC-B. La OS disminuyó de forma incremental en función de la mayor TBS (OS a 5 años; TBS baja: 77,9% versus TBS media: 61% versus TBS alta: 39%, P < 0,001). No se observaron diferencias en la OS entre pacientes con una puntuación TBS similar, independientemente del estadio BCLC (BCLC-A/TBS media: 61,6% versus BCLC-B/TBS media: 58,9%, P = 0,93; BCLC-A/TBS alta: 45,1% versus BCLC-B/TBS alta: 12,8%, P = 0,175). Los pacientes con BCLC-B/TBS media tuvieron una mejor OS que los pacientes con BCLC-A/TBS alta (58,9% versus 45,1%, P = 0,005). En el análisis multivariable, la TBS se mantuvo asociada a la OS en el caso de BCLC-A (TBS media: cociente de riesgos instantáneos, hazard ratio, HR = 2,07, i.c. del 95%: 1,42-3,02, P < 0,001; TBS alta: HR = 4,05, i.c. del 95%: 2,40-6,82, P < 0,001) y BCLC-B pacientes (TBS alta: HR = 3,85, i.c. del 95%: 2,03-7,30, P < 0,001). La TBS también pudo estratificar el pronóstico entre pacientes en una cohorte de validación externa (OS a 5 años; TBS baja: 78,7% versus TBS media: 51,2% versus TBS alta: 27,6%, P = 0,01). CONCLUSIÓN: El pronóstico de los pacientes con HCC varió según el estadio BCLC, pero dependió en gran medida de la TBS.

Hepatocellular Carcinoma in the Setting of Chronic Hepatitis B Virus Infection: Tumor Recurrence and Survival Rates After Liver Transplantation.

BACKGROUND: Higher rates of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in patients with chronic hepatitis B virus (HBV) infection have been reported. This can influence their selection for LT and post-LT monitoring. OBJECTIVE: The aim of this work was to compare the rates of post-LT HCC recurrence and survival in HBV and non-HBV patients with the use of the United Network for Organ Sharing (UNOS) database. METHODS: After accessing the UNOS database, we analyzed patients with HCC stage T2 who underwent LT from cadaveric donors on or after August 24, 1998. Propensity score matching based on age, Model for End-Stage Liver Disease (MELD), and donor risk index was used to match HBV-HCC patients to HCC patients with other underlying liver diseases: hepatitis C virus (HCV), alcoholic liver disease (ALD), both HCV + ALD, and nonalcoholic steatohepatitis (NASH). Kaplan-Meier plots and multivariable analysis (with the use of propensity score, age, sex, and race) were used to assess post-LT HCC recurrence and overall survival. RESULTS: A total of 4,480 HCC patients were matched. Their average age was 57 ± 7.8 years and average calculated MELD score was 13. Within 5 years of LT, 5.5% of patients had HCC recurrence and 20% died. HBV-HCC patients had 1.9 and 1.8 times higher hazard of tumor recurrence compared with ALD and NASH patients, respectively, and a 32% lower hazard of death than patients with HCV + ALD. There was no evidence of any other significant difference in HCC recurrence or survival among the etiology groups. CONCLUSIONS: HCC recurrence and survival rates following LT for HCC patients with chronic HBV infection are similar to those of HCC patients with other underlying liver diseases. These findings support LT as a viable option for HCC-HBV patients.

Split liver transplantation using Hemiliver graft in the MELD era: a single center experience in the United States.

Under the "sickest first" Model for End-Stage Liver Disease (MELD) allocation, livers amenable to splitting are most often allocated to patients unsuitable for split liver transplantation (SLT). Our experience with SLT using hemilivers was reviewed. From April 2004 to June 2012, we used 25 lobar grafts (10 left lobes and 15 right lobes) for adult-sized recipients. Twelve recipients were transplanted with primary offers, and 13 were transplanted with leftover grafts. Six grafts were shared with other centers. The data were compared with matched whole liver grafts (n = 121). In 92% of donors, the livers were split in situ. Hemiliver recipients with severe portal hypertension had a greater graft-to-recipient weight ratio than those without severe portal hypertension (1.96% vs. 1.40%, p < 0.05). Hemiliver recipients experienced biliary complications more frequently (32.0% vs. 10.7%, p = 0.01); however, the 5-year graft survival for hemilivers was comparable to whole livers (80.0% vs. 81.5%, p = 0.43). The secondary recipients with leftover grafts did not have increased incidences of graft failure (p = 0.99) or surgical complications (p = 0.43) compared to the primary recipients. In conclusion, while routine application is still controversial due to various challenges, hemiliver SLT can achieve excellent outcomes under the MELD allocation.

Combined intestine and kidney transplantation in a patient with encapsulating peritoneal sclerosis: case report.

Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis characterized by fibrosis and calcification of the intestine that, in severe cases, can progress to intestinal failure and total parenteral nutrition dependency. Medical and surgical interventions carry a poor prognosis in these patients. We describe a case of a 36-year-old female with end-stage kidney disease and severe EPS not amenable to surgical intervention who underwent a combined intestinal and kidney transplantation. At 3 years posttransplantation, the patient has normal intestinal and kidney function. This represents, to our knowledge, the first report of severe EPS and end-stage kidney disease treated with a combined transplant.

Adjuvant treatment of hepatocellular carcinoma after orthotopic liver transplantation: do we really need this?

Hepatocellular carcinoma (HCC) continues to rise and is still a major cause of mortality. Orthotopic liver transplantation (OLT) continues to give patients the best chance for cure, but recurrence of the disease remains a problem. Even with the implementation of the Milan criteria, recurrence rates have been shown to be 8-15% in most studies and even higher in patients who are beyond the Milan criteria. Therefore, several investigators have looked into the value of adjuvant therapy using systemic cytotoxic chemotherapy in HCC after OLT. Unfortunately, most of the trials are very small, and the results have been disappointing. But trials using Licartin seem to be promising, and other drugs such as FOLFOX and sorafenib warrant further investigation based on their efficacy in the advanced disease. In this review, we will review the current data on efficacy and rationale of adjuvant treatment for HCC after OLT including novel biomarkers.

Serum vascular endothelial growth factor level in patients with hepatocellular carcinoma undergoing liver transplantation: experience of a single Western center.

BACKGROUND: The strongest predictor of tumor relapse after liver transplantation for hepatocellular carcinoma (HCC) is vascular invasion, appreciated only on explant analysis. High serum level of vascular endothelial growth factor (VEGF) is associated with worse outcomes after resection or locoregional therapies but its role in liver transplantation remains undefined. OBJECTIVE: We report the first western prospective study exploring serum VEGF in HCC liver transplant patients, correlating pre-operative serum VEGF with poor prognostic histologic features during explant analysis. METHODS: Between May 2008, and June 2010, 75 HCC patients underwent liver transplantation at our institution. Serum VEGF was measured every 3 months until liver transplantation and correlated with histopathologic findings on explant. RESULTS: There was no significant correlation between pre-transplant serum VEGF levels and tumor burden (median 31.0 pg/mL vs. 42.5 pg/mL, p=0.33, for tumors within and beyond the Milan criteria, respectively). Pre-transplant VEGF levels were higher in poorly differentiated tumors compared to well to moderately differentiated tumors, but not statistically significant (median 49.0 pg/mL vs. 31.0 pg/mL, p=0.26). Pre-transplant VEGF did not correlate with vascular invasion (median 37.0 pg/mL vs. 31.0 pg/mL, p=0.35, in the presence and absence of vascular invasion, respectively). CONCLUSION: Pre-operative serum VEGF fails to predict unfavorable histologic HCC features in patients undergoing liver transplantation. Role of serum VEGF in liver transplant HCC patients remains unclear.

Liver Transplantation for Hepatocellular Carcinoma among African Americans in the United States.

BACKGROUND: There is increased prevalence of hepatocellular carcinoma (HCC) among African Americans (AA). Multicenter studies have shown advanced presentation, underutilization of treatment and decreased survival following liver transplantation (LT) among AA. However outcomes from single centers are not well reported. OBJECTIVE: To determine the outcome of AA undergoing LT for HCC at Cleveland Clinic, Cleveland, Ohio, between May 2007 and December 2009. METHODS: 245 consecutive patients undergoing evaluation and treatment for HCC within the mentioned time frame were studied, retrospectively. RESULTS: 80% of patients were male, 75.5% were Caucasian, 16.7% were AA and 7.8% were other ethnic groups. Compared to other ethnicities, AA subjects with HCC were more commonly female and were more likely to have hepatitis C virus (HCV) (83% vs. 51%, p<0.001). There were higher occurrence of HCV genotype 1 among AA compared to others among patients with this information (100% vs. 65%, p<0.001). In contrast to previous reports, there was no significant difference between the groups in terms of clinical presentation or management. 27% of AA underwent liver transplantation compared to 28% of the rest (p=0.88). Of the 68 patients who had LT, 9% died with no difference in post-LT survival between the two groups. CONCLUSIONS: HCV (and genotype 1) is a significant risk factor for HCC in the AA population. LT results in similar survival compared to other ethnicities. AA patients with HCC benefit equally from LT compared to other ethnicities.

Rate of tumor growth predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria.

BACKGROUND: It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC). METHODS: We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed. RESULTS: Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7-30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P=.001), poorly differentiated tumors (HR 13; P=.039), the presence of microvascular invasion (HR 7.9; P=.001), higher TTV (HR 1.03; P<.001), and faster tumor growth (HR 1.09; P<.001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm3/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth<1.61 cm3/mo experienced less recurrence (11% vs 58%; P=.023) than those beyond the Milan criteria with tumor growth>1.61 cm3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria. CONCLUSIONS: Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.

Total tumor volume predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria.

BACKGROUND: The aim of tumor-based selection criteria in patients with hepatocellular carcinoma (HCC) is to prevent orthotopic liver transplantation (OLT) in patients likely to experience recurrence and to maximize OLT opportunities for those with a high likelihood of cure. OBJECTIVE: Our aim was to assess total tumor volume (TTV) as a selection criterion for OLT in patients with HCC beyond Milan or University of California San Francisco criteria. METHODS: We identified patients who underwent OLT for HCC between 2002 and 2008. TTV was calculated as the sum of the volumes of all tumors on pretransplant imaging before any therapy [(4/3)πr(3), where r is the maximum radius of each HCC]. Univariable and multivariable Cox proportional hazards regression analysis was used to assess factors associated with recurrence of HCC. RESULTS: 107 patients were included in the study. The mean follow-up was 21 months (interquartile range, 11.8-32.5), during which 13 patients (12.1%) experienced recurrence of HCC. Twenty-nine patients (27.1%) had HCC beyond the Milan criteria. A TTV cutoff value of 33.5 cm(3) was chosen on the basis of the risk of recurrence by using a receiver operating characteristic curve. Patients beyond the Milan criteria with TTV <33.5 experienced less recurrence (13.3% vs 42.8%; P < .001) and higher survival (13.3% vs 57.1%; P = .006) than those who were beyond the Milan criteria with TTV ≥33.5. Similarly, TTV predicted HCC recurrence and survival in those beyond the UCSF criteria. CONCLUSION: TTV is useful in identifying patients at risk of tumor recurrence and poor survival among those with tumor burden beyond traditional criteria, and it may improve the selection of OLT candidates.

Use of tissue plasminogen activator in liver transplantation from donation after cardiac death donors.

Ischemic-type biliary stricture (ITBS) occurs in up to 50% after liver transplantation (LT) from donation after cardiac death (DCD) donors. Thrombus formation in the peribiliary microcirculation is a postulated mechanism. The aim was to describe our experience of tissue plasminogen activator (TPA) administration in DCD-LT. TPA was injected into the donor hepatic artery on the backtable (n = 22). Two recipients developed ITBS including one graft failure. Although excessive postreperfusion bleeding was seen in 14 recipients, the amount of TPA was comparable between those with and without excessive bleeding (6.4 ± 2.8 vs. 6.6 ± 2.8 mg, p = 0.78). However, donor age (41 ± 12 vs. 29 ± 9 years, p = 0.02), donor BMI (26.3 ± 5.5 vs. 21.7 ± 3.6 kg/m(2) , p = 0.03), previous laparotomy (50% vs. 0%, p = 0.02) and lactate after portal reperfusion (6.3 ± 4.6 vs. 2.8 ± 0.9 mmol/L, p = 0.005) were significantly greater in recipients with excessive bleeding. In conclusion, the use of TPA may lower the risk of ITBS-related graft failure in DCD-LT. Excessive bleeding may be related to poor graft quality and previous laparotomy rather than the amount of TPA. Further studies are needed in larger population.