Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.     

Results of orthotopic liver transplantation for liver cirrhosis in the presence of incidental and/or undetected hepatocellular carcinoma and tumour characteristics

Abstract Orthotopic liver transplantation (OLT) for liver cirrhosis in the presence of hepatocellular carcinoma (HCC) is based on tumour number and size. The high incidence of undetected HCC before OLT has been reported previously. The object of this work to report the results of OLT for liver cirrhosis in the presence of incidental and/or undetected HCC and tumour characteristics. From 1985 to 1996, 334 patients received OLT. Two groups of patients were studied; group 1 (G1) where HCC was diagnosed on radiological examination before OLT ( n = 13, mean age 53.8 ± 8.1 years), and group 2 (G2), where HCC was diagnosed on pathological review ( n = 13, mean age 53.3 ± 6.1 years). Indications for OLT were (G1/G2) hepatitis C = 6/8, hepatitis B = 5/2, alcoholic = 2/3. There was no statistically significant difference in α-foetoprotein levels between both groups. Pathological review showed 26 and 30 HCC with a mean size of 1.6 ± 0.8 and 1.6 ± 1.2 cm ( P > 0.05) in G1 and G2, respectively. Tumour stagings were (G1/G2) stage I = 6/2, stage II = 4/6, stage III = 2/3, stage IVa = 1/2. We had two (G2) hospital and three (G1) later mortalities; none had HCC recurrence. The other patients are alive and recurrence free. Reinforced immunosuppression related to acute or chronic rejection treatment was not associated with HCC recurrence. The 5-year actuarial survival rates were 76% for G1 and 85% for G2 ( P > 0.05). Our study revealed that long-term survival can be achieved with liver transplantation in the presence of HCC in carefully selected patients.     

Liver transplantation in primary and secondary tumors of the liver. Review of the literature and perspectives

Liver transplantation for malignancies still remains a controversial issue. There is concern for tumour recurrence, poor results and waste of organs, which in the sitting of organ shortage would penalize patients with non-malignant disease. Many centers worldwide perform liver transplantation (OLT) for hepatocellular (HCC) carcinoma associated with liver cirrhosis; the results in these cases are similar to those of patients transplanted for other indications. On the contrary are very few the centers that perform OLT for tumour other than HCC. This reflects that tumours other than HCC are less common and survival is poor compared to patients transplanted for non-malignant disease. Acceptable indications for OLT in case of tumours other than HCC are liver metastases from neuroendocrine tumours and epithelioid emangio-endothelioma. However should be kept in mind that OLT may offer the sole opportunity to cure the tumour and the underlying disease in some patients while providing meaningful palliation for others. At the present the overall experience with OLT for tumours other than HCC is still not significant and the results are discouraging. There is no evidence that OLT is beneficial for non-HCC tumours. Hopefully for the next future new adjuvant and neoadjuvant therapies combined with OLT would provide improved survival. Nevertheless, long-term survivors continue to be reported suggesting that OLT may be beneficial in individual selected cases with non-HCC tumour.     

Recurrence-free survival after liver transplantation for small hepatocellular carcinoma

Abstract Recurrence-free survival (RFS) in patients with small hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) was analyzed. From 1988 until 1996, 725 OLTs were performed in 669 patients. In 52 adults, HCC was confirmed histologically. OLT was limited to patients with small (<5 cm) HCC with a maximum number of three nodules. Actuarial survival for these 52 patients at 1 and 5 years is 88% and 71%. RFS was defined as time until death without recurrence, time until follow up with a diagnosis of recurrence, or, in patients without recurrence, time of last follow up. Overall, the 5-year RFS was 60%. Five-year RFS was less for bilobar compared to unilobar tumors (36% vs 70%), less for stage IVa tumors (UICC) compared to stage I-III tumors (17% vs 71%), and less for multiple compared to solitary tumors (54% vs 67%). In conclusion, potential cure may be achieved in more than 50% of all transplanted patients.     

Surgical Treatment of Hepatocellular Carcinoma beyond Milan Criteria. Results of Liver Resection, Salvage Transplantation, and Primary Liver Transplantation

Background There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC). Methods Patients with cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary orthotopic liver transplantation (OLT) between November 1995 and December 2005 were included in this study. Pathological tumor staging was based on the American Liver Tumor Study Group modified Tumor-Node-Metastasis classification. Results A total of 23 HCC patients were primarily treated by means of LR, 5 of whom eventually underwent salvage OLT. An additional 32 patients underwent primary OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and 69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years was significantly higher after OLT (65%) than after LR (26%). Of the patients who underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these 11 presented with advanced HCC recurrence, poor medical status, or short disease-free intervals and were not considered for transplantation. Salvage OLT was performed in 5 patients with early stage recurrence (45% of patients with hepatic recurrence after LR and 22% of all patients who underwent LR). At a median of 18 months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1 developed HCC recurrence 16 months after salvage OLT. Conclusion For patients with HCC beyond Milan criteria, multimodality treatment—including LR, salvage OLT, and primary OLT—results in long-term survival in half of the patients. When indicated, LR can optimize the use of scarce donor organs by leaving OLT as a reserve option for early stage HCC recurrence.     

Perioperative Blood Transfusion as a Prognostic Indicator in Patients with Hepatocellular Carcinoma

We studied the relation of perioperative blood transfusion and the outcomes in 175 patients with hepatocellular carcinoma (HCC) who underwent hepatic resection from 1986 to 1994 in our hospital. Hepatectomy was performed in 23 (13.1%) patients with and 152 (86.9%) without blood transfusions. The cumulative cancer-free survival rates for patients who had received blood transfusion was significantly lower than that for patients who had not received blood transfusions (p= 0.003). Further examinations revealed a significant difference in cancer-free survival rates for stage I–II patients (n= 75) of HCC (p= 0.02) but not for stage III–IV patients (n= 56) (p= 0.06). Cox regression analysis for recurrence revealed that blood transfusion was the most significant prognostic indicator (p= 0.001) for recurrence in stage I–II patients but not in stage III–IV patients (p= 0.99). These results suggest that a perioperative blood transfusion may be a significant prognostic indicator for patients with HCC who had underwent hepatectomy, especially in stage I–II patients of HCC.     

Twenty-year experience with liver transplantation for hepatocellular carcinoma

HYPOTHESIS: Liver transplantation (LT) has become the optimal treatment for stages I and II hepatocellular carcinoma (HCC). Based on our 20-year experience, changes in staging, techniques, and patient selection have improved survival over the past 20 years. Herein, we determine if pre-LT treatment for HCC alters the long-term outcomes in patients with HCC. DESIGN: Outcomes study. SETTING: Tertiary referral center. PATIENTS: We retrospectively reviewed prospectively collected data in a cohort of 92 patients who underwent LT for HCC between 1983 and 2003. MAIN OUTCOME MEASURES: Patient demographics, tumor stage in the explant liver, patient survival, and tumor recurrence data were analyzed. RESULTS: The average follow-up was 1052 (range, 0-6491) days. The average tumor size was 3.6 cm; 40% of tumors were multifocal and 60% unifocal. Of the 92 patients, 26% were classified as stage I; 42%, stage II; 24%, stage III; and 8%, stage IV. The overall 5-year survival rate was 50%, the 10-year survival rate was 32%, and the 15-year survival rate was 27%. Improvements in staging in the last 5 years reduced the number of patients with stages III and IV HCC from 39% to 19% and increased the 5-year survival rate to 69%. Tumor recurrence was relatively rare (13%); however, recurrence resulted in a poor prognosis (75% mortality rate; P = .02). The average time to recurrence was 458 (range, 179-1195) days. CONCLUSIONS: Liver transplantation for HCC results in excellent long-term survival for patients with stages I and II HCC, with relatively few patients dying from tumor recurrence. Improvements in preoperative staging have resulted in increased 5-year survival rates. Further refinements in pre-LT staging may increase the effectiveness of LT for HCC.     

LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS

Background : Hepatocellular carcinoma (HCC) in patients with cirrhosis, due to a limited liver reserve, is often deemed unresectable, even at an early stage. Methods : In order to evaluate the ongoing transplant programme for cirrhotic patients with HCC at Royal Prince Alfred Hospital, the results of liver transplantation (LTx) for HCC were analysed and the patient actuarial survival was compared with that of those LTx patients without malignancy. Results : A total of 441 LTx were performed in 404 patients between January 1986 and April 1998. Twenty-four LTx recipients (22 men; two women) of mean age 49 (15–62) years had HCC. Twenty-one had underlying aetiology for their cirrhosis (hepatitis B: n = 9; hepatitis C: n = 8; hepatitis B and C: n = 1; haemochromatosis: n = 1; autoimmune hepatitis: n = 1; alcoholism: n = 1), while three patients had cryptogenic cirrhosis. Six patients had incidental tumours and another two cases were of the fibrolamellar type. The average tumour size and tumour number were 2.9 (0.4–11.5) cm and 1.3 (1–4), respectively. Operative mortality was 4.2% (1/24). The HCC recurrence appeared in one (4.2%) patient (with a 11.5-cm HCC) who died 18 months after LTx. A further two patients died (one graft failure from recurrent hepatitis C and one from fungal sepsis) during follow-up. The overall 1- and 3-year actuarial patient survival rates were 87% and 76%, respectively, and that of patients with benign causes (n = 369) were 77% and 72% (P = NS). Conclusion : With careful patient selection, long-term tumour-free patient survival can be achieved. The results support an active transplant programme for selected HCC.     

The primary management of breast cancer: is breast conservation feasible for all patients?

A consecutive series of 411 patients with primary breast cancer treated by a consistent policy of breast conservation, regardless of tumour size, location, clinical stage or histological subtype, is reported. Actuarial 5-year survival was 84% for UICC Stage I, 73% for Stage II and 47% for Stage III/IV. The incidence of local recurrence at 5 years was 13% for Stage I, 12% for Stage II, and 26% for Stage III/IV. The probability of salvage mastectomy at 5 years was 5% for Stage I, 8% for Stage II, and 15% for Stage III/IV. Of local recurrences, 40% were managed with further breast conservation. Primary treatment with breast conservation results in satisfactory local control rates, 5-year survival and cosmesis, but the prevention, diagnosis and treatment of local recurrence within the conserved breast requires further evaluation.     

The best management of superficial bladder tumours: Comparing TUR alone versus TUR combined with intravesical chemotherapy modalities?

To compare retrospectively the recurrence rates of TUR alone versus different intravesical chemotherapy modalities in superficial bladder cancer cases, 187 patients with stage Ta and T₁ bladder tumours were treated with transurethral resection followed by adjuvant intravesical chemotherapy with mitomycin, BCG or epirubicin or by transurethral resection alone. All patients in this study had historically proven transurethrally resectable primary, category Ta and T₁ transitional cell carcinoma (TCC) of the bladder. Group I included transurethral resection alone, and the other groups included intravesical mitomycin-C(Group II), BCG (Group III) and epirubicin (Group IV) therapies after transurethral resection. 146 male and 41 female patients (78% male and 22% female patients) in this study were diagnosed as primary TCC bladder tumours. Only 52 of them were stage Ta and 135 of them were stage T₁ bladder tumours. Examining the histological grade of the bladder tumours, 88 (47%) of the patients had grade I, 53 (28%) had grade IIa, 30 (16%) had grade IIb and remaining 16 (9%) had grade III bladder cancers. The recurrence rates were 25% for Group I, 23.8% for Group II, 26.2% for Group III and 22.7% for Group IV. These values were given with disregarding the grade and volume of the bladder tumours. For solitary, less than 3 cm low grade tumours (grade I, IIa) recurrence rates were 16% for Group I, 15.4% for Group II, 17.8% for Group III, 17.2% for Group IV (p> 0.05). As a result of this retrospective study, for patients with low grade, stage Ta and T₁ tumours TUR alone may be the best treatment modality. Although intravesical chemotherapy is effective in decreasing short-term incidences of tumour recurrence, it has not decreased long-term incidences of tumour recurrence. The high cost and adverse side effects of intravesical chemotherapy should also be taken into consideration in superficial, single, low grade tumours of bladder. This revised version was published online in August 2006 with corrections to the Cover Date.     

Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the effect of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Historically, liver transplantation for HCC has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. METHODS: Twenty-five patients were placed on 6 months of intravenous fluorouracil, doxorubicin, and cisplatin after OLT. Risk factors, recurrence rates, and survival rates were analyzed and compared with historic controls. RESULTS: Overall long-term survival in the protocol patients was 46% at 3 years, improved over our historic controls of 5.8% at 3 years (p = 0.0001). Overall recurrence rate was 20% (n = 4). Possible risk factors, such as tumor size, vascular invasion, multifocality, capsular invasion, and tumor differentiation, were not found to be significantly predictive of survival. Three patients with long-term, disease-free survival had tumors > 5 cm. Side effects from chemotherapy were common, but rarely severe. CONCLUSIONS: This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease.     

Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival

BACKGROUND: Preorthotopic liver transplantation locoregional therapy (LRT) for hepatocellular carcinoma (HCC) reduces drop-out rates in patients awaiting orthotopic liver transplantation (OLT). In this study, we investigated the efficacy of LRT as a strategy to improve longterm survival after transplantation. STUDY DESIGN: A retrospective analysis of prospectively collected data identified 100 patients with HCC who underwent OLT between 1985 and 2005. Of these, 46 received LRT in the form of transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or a combination of these. RESULTS: The 1-, 3-, and 5-year survivals, regardless of LRT, were 81.3%, 66.1%, and 61.3%, respectively. Demographic data and waiting time for OLT were similar between LRT and untreated groups. Pre-OLT radiologic stage was comparable (LRT: 2.11 +/- 0.74 versus Untreated: 2.39 +/- 0.94; p = 0.16). At the time of transplantation, the LRT group had notable tumor downstaging (1.50 +/- 1.34 versus 2.49 +/- 1.17; p = 0.008). The LRT group had better 5-year survival (82.4% versus 51.8%; p = 0.01), but this improvement was observed in patients with HCC stages II, III, and IV (77.6% versus 37.4%; p = 0.016). Sixteen LRT patients, and none untreated, revealed complete tumor necrosis with no viable tumor cells on explant pathology (pT0). These patients did not experience any longterm recurrence, in contrast to those with similar pre-OLT tumors. CONCLUSIONS: OLT is a viable treatment option for primary HCC. LRT substantially downstages the primary tumor and improves longterm survival in patients with advanced disease. Complete tumor necrosis with LRT is associated with excellent longterm recurrence-free survival.     

Multimodal therapy for colon cancer: state of the art

In UICC stage I a selected group of patients with T1 tumours and a low risk profile regarding simultaneous lymph node metastases can be treated by endoscopic resection alone, if the tumour is thereby completely removed. In UICC stage II an adjuvant chemotherapy (CT) should not be routinely performed. However, in high risk UICC stage II patients (T4 tumour, less than 12 examined lymph nodes, emergency surgery, intraoperative tumour perforation), an adjuvant CT with infusional 5-FU/FA should be recommended. The state of the art in UICC stage III is an adjuvant CT with FOLFOX. In this tumour stage no beneficial effect of CT involving irinotecan or monoclonal antibodies has been documented. Due to CT-induced side effects an infusional 5-FU/FA protocol or oral capecitabine should be given in patients older than 70 years. In stage UICC IV with resectable liver metastases, surgical resection of the primary tumour and the metastases should be implemented. Since no conclusive data are currently available regarding the beneficial effect of neoadjuvant, perioperative or adjuvant CT in this setting, the therapeutic strategy should be individually discussed between surgeons and oncologists (tumour board). In cases of non-resectable liver metastases a neoadjuvant CT should be performed, preferentially with a FOLFOX protocol in combination with targeted therapies, i.e., the monoclonal antibody cetuximab, aimed at tumour regression with radical metastasectomy as the secondary intent (R0). Patients with UICC stage II colon cancer and microsatellite instability (MSI) apparently experience a better prognosis but do not profit from an adjuvant CT with 5-FU/FA alone. If a CT is under consideration for these patients, the MSI status should be determined on tumour tissue. In cases of a positive result a combination CT, i.e., with FOLFOX, should be given. The relevance of the MSI status in other tumour stages is as yet unknown. Before targeted therapies, i.e., cetuximab or panitumumab, are initiated, the KRAS status needs to be determined, since therapies with antibodies against the epithelial growth factor receptor (EGFR) are only effective in tumours bearing the KRAS wild-type.     

Clinical outcomes of liver transplantation for HBV-related hepatocellular carcinoma: data from the NIH HBV OLT study

Han SH, Reddy KR, Keeffe EB, Soldevila‐Pico C, Gish R, Chung RT, Degertekin B, Lok ASF. Clinical outcomes of liver transplantation for HBV‐related hepatocellular carcinoma: data from the NIH HBV‐OLT study.
Clin Transplant 2011: 25: E152–E162. © 2010 John Wiley & Sons A/S. Abstract: Background: Hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV‐related HCC is increasing, while the number of patients listed for HBV‐related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long‐term outcome of patients transplanted for HBV‐related HCC in the National Institutes of Health (NIH) HBV OLT Study Group. Results: Ninety‐eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV‐related HCC. With a mean follow‐up of 36.5 months post‐OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre‐OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre‐OLT in predicting HCC recurrence. Serum alpha‐fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p = 0.003). HCC recurrence was significantly associated with decreased post‐OLT survival. Conclusion: HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence.     

The Influence of High Serum Testosterone Levels on the Long-term Prognosis in Male Patients Undergoing Hepatectomy for Early Stage Hepatocellular Carcinoma without Vascular Invasion

Background The influence of high serum testosterone levels on the long-term prognosis in male patients undergoing hepatectomy for hepatocellular carcinoma (HCC) remains to be fully elucidated. The aim of the present study was to conduct a retrospective investigation of the impact of high serum testosterone levels on the risk of tumor recurrence and long-term prognosis in male patients undergoing hepatectomy for early stage HCC without vascular invasion. Methods Between August 1995 and March 1999, 42 male patients undergoing curative hepatectomy for HCC of tumor-node-metastasis (TNM) stages I and II without vascular invasion were enrolled in the study. Preoperative serum testosterone concentration was measured. The clinicopathological features, tumor recurrence rates, and 5-year disease-free and actuarial survival after hepatectomy were compared between the patients with serum testosterone levels in the upper half (group I, n = 21) and the patients in the lower half (group II, n = 21). Results The background and clinicopathological features did not differ significantly between groups I and group II. All survivors were followed up for more than 5 years. Until March 2005, patients in group I, with serum testosterone levels in the upper half, had a significantly higher percentage of 5-year tumor recurrence than group II, with lower testosterone levels (76.2% versus 28.6%; p < 0.005). The patients in group I also had a significantly inferior 5-year disease-free (p < 0.01) and actuarial (p < 0.05) survival rates than patients in group II. Conclusions Male patients with high serum testosterone levels undergoing hepatectomy for early stage HCC without vascular invasion have significantly higher 5-year tumor recurrence rates and an inferior long-term prognosis than patients with low testosterone levels. These findings signal a strategy of adjuvant anti-androgen treatment selectively targeted for the male patients with high serum testosterone levels after hepatectomy for early stage HCC without vascular invasion to achieve better long-term outcome.     

Liver transplantation for hilar cholangiocarcinoma: Spanish experience

INTRODUCTION: Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival. METHODS: We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. RESULTS: The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P<.001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P<.05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P<.01) and stages III to IVA (P<.01). CONCLUSION: OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.     

The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation

Zimmerman MA, Kelly MA, Campsen J, Mandell MS, Wachs M, Bak T, Skibba A, Lancaster B, Kam I. The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation.
Clin Transplant 2010: 24: E103–E108.
© 2009 John Wiley & Sons A/S. Abstract: Introduction:  Cancer recurrence following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is a significant obstacle in up to 10–20% of recipients. Recent evidence suggests that anti‐CD3 antibody (OKT3) therapy may be associated with increased rates of HCC recurrence. Methods:  At the University of Colorado Transplant Center, 173 patients underwent OLT for end‐stage liver disease with concomitant HCC between 1997 and 2008. Nine clinical and pathologic variables were analyzed to test the association between OKT3 therapy for steroid‐resistant rejection (SRR) and HCC recurrence‐free survival. Results:  Overall, the rate of HCC recurrence in this cohort was low and comparable across treatment groups (8.7%). Multivariate analysis reveals that increasing tumor diameter and differentiation have a negative impact on HCC recurrence‐free survival. Conclusions:  While several pathologic variables appear to influence outcome, we found no association between OKT3 therapy for SRR and HCC recurrence or survival.     

Comparison of clinical outcomes in chronic hepatitis B liver transplant candidates with and without hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) receive a higher MELD score and may undergo liver transplantation (OLT) earlier compared to patients with cirrhosis, potentially decreasing waiting list mortality. However, post-OLT survival may be reduced by recurrence of HCC. We compared clinical outcomes between patients with HBV-cirrhosis and no HCC and patients with HBV-HCC. A total of 279 patients (HBV-cirrhosis = 183; HBV-HCC = 96) in the US HBV-OLT study were followed for a median of 30.2 months from listing. Patients with HCC were older, more likely to be Asian, and had less severe liver impairment than patients with HBV-cirrhosis. Despite a higher rate of OLT in patients with HCC (78.1% vs. 51.4%; P < 0.001), intention-to-treat (ITT) survival (73% vs. 78%) and survival without OLT (82% vs. 79%) at 5 years were similar for patients with and without HCC. Cox regression analysis identified higher albumin, lower MELD, no HCC at listing, and being transplanted to be associated with better ITT survival. Ninety-four patients with HCC (including 19 new HCC) and 75 with HBV-cirrhosis underwent OLT. Post-OLT survival (83% vs. 90%) and HBV recurrence (11% vs. 10%) at 3 years were similar, while disease (HBV and/or HCC) recurrence (19% vs. 10%; P = 0.043) was higher in patients with HBV-HCC vs. HBV-cirrhosis. Disease recurrence was the only independent predictor of post-OLT survival. In conclusion, despite more advanced liver disease and a lower rate of transplantation, ITT survival of patients listed for HBV-cirrhosis was comparable to those with HBV-HCC, possibly related to beneficial effects of antiviral therapy.     

Selection of small hepatocellular carcinoma improves long-term results of hepatic transplantation for malignancy

Abstract Liver transplantation for advanced hepatocellular carcinoma is often followed by early tumour recurrence and death. At the beginning of the liver transplantation programme at Berlin Virchow we decided to offer liver transplantation only to patients with solitary tumours not exceeding a maximum diameter of 5 cm or to patients with two or three tumour nodes with a maximum diameter of 4 cm. From September 1988 to October 1993 435 liver transplants were performed in 403 patients. Of these, 32 patients (8 %) had a histologically confirmed hepatocellular carcinoma (29 males, 3 females, median age 56 years). The overall actuarial survival according to Kaplan-Meier for the whole series of 32 patients with hepatocellular carcinoma was 82%, 78%, and 78% at 1, 2 and 3 years, respectively. Tumour size alone did not seem to be a relevant factor when comparing patients with tumours up to or larger than 3 cm in diameter. Patients with solitary tumours had a better prognosis than patients with multiple tumours. The largest difference was found between patients with stage I-III (UICC) tumours and those with stage IVA tumours: 1-, 2- and 3-year survival rates were 89% throughout in the former group, while the corresponding figures for patients with stage IVA tumours were 63%, 47% and 47%. Efforts should be made to identify stage IVA tumours preoperatively in order to use the precious resource of scarce donor livers in an optimal way.     

原发性肝癌与非肝癌病人行肝移植治疗的比较研究

目的：探讨我国目前肝癌与非肝癌病人行肝移植治疗的风险及长期生存效果。方法：回顾性总结21例晚期肝癌病人行肝移植手术治疗风险及长期生存情况，并与同期所行另外19例非肝癌病人的肝移植进行比较。结果：晚期肝癌病人的手术前凝血状态好于因其它非肝癌原因而接受肝移植的病人，与此相应的手术中出血量、需要输血量、术中输液总量均少于非肝癌病人，手术中因出血而导致的低血压时间短，手术后较恢复顺利，围手术期病死率低。虽然肿瘤复发所致的远期死亡率明显高于非肝癌病人，但是，总生存率与非肝癌病人无明显区别，部分病人可长期无瘤生存。结论：现阶段肝移植仍是失去根治性切除机会的肝癌病人的有效治疗手段，术后部分病人有无瘤长期生存的可能性。