Intrahepatic Recurrence Of Hepatocellular Carcinoma Research Articles

Repeated liver resection for recurrent hepatocellular carcinoma

Tumor recurrence after liver resection occurs in the majority of patients with hepatocellular carcinoma (HCC). This study was conducted to clarify the safety and effectiveness of repeated liver resection as a curative option for intrahepatic HCC recurrence. Between July 1990 and January 2009, 483 patients underwent 514 curative hepatic resections for HCC in our institution. Among this collective, 27 patients underwent 31 repeated resections due to recurrent HCC (27 s resections, three third resections and one forth resection). The outcome of these patients was retrospectively reviewed using a prospective database. Perioperative morbidity and mortality was 11% (three of 27) and 0%. Six patients showed multiple liver lesions, 23 underwent minor liver resections (fewer than three segments) and five patients underwent major resections (three or more segments). The majority of the patients showed no signs of chronic liver disease (16 of 27). The median tumor free margin was 1.5 mm (range: 0 to 20 mm). The median tumor diameter was 40 mm (range: 10 to 165 mm). Tumor dedifferentiations at time of tumor recurrence were not observed. The 1-, 3- and 5-year overall survival rates after second liver resection were 96%, 70% and 42%. Repeated liver resection is a valid and safe curative therapy option for recurrent HCC and results in significant prolongation of survival in comparison to interventional treatment strategies in selected patients. However, due to impaired liver function, multifocal intrahepatic or extrahepatic recurrence repeated resection is only feasible in a minority of patients.

Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma: impact on patient's prognosis

Percutaneous radiofrequency ablation (RFA) has been widely accepted as an alternative to surgery for small hepatocellular carcinoma (HCC). In RFA, a portion of liver tissue surrounding tumour is also ablated to achieve a safety margin. The intrahepatic bile duct may be injured and result in chronic bile duct dilatation upstream of the injured site. However, the impact of such an injury on the overall prognosis has been unclear. Patients who showed bile duct dilatation following RFA were identified by a retrospective review of imaging studies. Each dilatation was classified as mild (limited to one hepatic subsegment) or severe (affecting two or more subsegments). The relation between the incidence of intrahepatic bile duct dilatation and HCC recurrence or survival was analysed using proportional hazard models. Among 589 consecutive HCC patients treated with RFA, 70 (11.9%) and 21 (3.6%) patients showed mild and severe bile duct dilatation respectively. Patients with severe dilatation, but not those with mild dilatation, had lower survival and higher HCC recurrence than patients without dilatation. Severe dilatation, but not mild dilatation, was significantly associated with death [hazard ratio (HR) 2.17, P=0.035] and recurrence (HR 2.89, P<0.001). Whereas mild bile duct dilatation after RFA is clinically negligible, bile duct dilatation affecting two or more subsegments should be regarded as a complication that may affect the prognosis and should be observed carefully.

Intraoperative ultrasound patterns predict recurrences after surgical treatments for hepatocellular carcinoma

Introduction Hepatocellular carcinoma (HCC) is associated with a high incidence of postoperative recurrence, despite high rates of complete necrosis with radiofrequency ablation (RFA) and curative hepatic resections (HR). The aim of this study was to identify intraoperative ultrasound patterns observed during HR or RFA that predicting intrahepatic HCC recurrence. Materials and methods From January 1997 through August 2008, we treated 377 patients with HCC (158 with HR and 219 with surgical RFA). All patients underwent intraoperative ultrasound (IOUS) examination. Primary HCCs was classified according to diameter, HCC pattern (nodular or infiltrative), echogenicity (hyper- or hypo-), echotexture (homogeneous or inhomogeneous), capsular invasion, mosaic pattern, nodule-in-nodule appearance, and infiltration of portal vessels. Number of HCC nodules was also considered. Comparisons between the groups of possible factors for intrahepatic recurrence of treated tumors were performed using the Kaplan–Meier method and compared using the log-rank test. Results Patients were followed for 9–127 months (median: 18.6 months), and intrahepatic recurrence was observed in 198 (52.5%). In 138 patients (36.5%), recurrences were located in different segments with respect to the primary tumor. In 60 HCC tumors (16%), local recurrences were found in the same segment as the primary tumor. At univariate analysis, primary HCC echogenicity and mosaic pattern were the only factors not significant associated with intrahepatic recurrences. Conclusion IOUS is an accurate staging tool for use during “surgical” resection or RFA. This study shows that IOUS patterns can also be used to estimate the risk of post-treatment HCC recurrence. In patients at high risk for this outcome, closer follow-up and use of adjuvant therapies could be useful.

A Prognostic Model and Treatment Strategy for Intrahepatic Recurrence of Hepatocellular Carcinoma after Curative Resection

The aim of this study was to evaluate the prognostic factors for intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resection. Of 297 patients with HCC who underwent curative resection between 1998 and 2007, 145 had intrahepatic recurrence, and 125 of these were enrolled in this study. We analyzed the relationships between overall survival after HCC recurrence and 20 variables at initial hepatectomy and recurrence. Recurrent HCC was treated by repeat hepatectomy (Re-Hr, n = 29), radiofrequency ablation (RFA, n = 58), or transarterial chemoembolization (TAE, n = 38). Complete tumor control (CTC) by Re-He and RFA was selected for 70% of patients. RFA-treated patients had more tumors, smaller tumors, and poorer liver function at recurrence than the Re-Hr group. The overall 1-, 3-, and 5-year post-recurrence survival rates (SR) were 93.1, 66.8, 58.1%; 94.7, 75.1, 48.3%; and 80.1, 22.5, 0%, respectively, in the Re-Hr, RFA, and TAE groups. The SR was better for Re-Hr and RFA than for TAE (p < 0.0001). Outcomes were similar in Re-Hr and RFA, regardless of recurrent tumor size. Multivariate analysis identified Child-Pugh grade B, AFP ≥100 ng/ml at recurrence, recurrent tumor size ≥3 cm, tumor number ≥3, and CTC as significant prognostic factors for overall post-recurrence survival. A scoring system using 1 point for each patient-background factor provided a well-categorized predictive model. The overall 3-/5-year post-recurrence SRs were 83.1/59.3%, 64.1/41.9%, 42.0/18.0%, and 13.6/0% at risk number (R) R0, R1, R2, and R3/4, respectively (p < 0.05). Significant prognostic factors for intrahepatic recurrent HCC are poor hepatic reserve, AFP, recurrent tumor size and number, and CTC. Selection of treatment modality for intrahepatic recurrence requires the clinician to be mindful of the predictive factors and to control tumors aggressively by adequate treatment, selected by balancing various conditions.

Differentiating the impact of anatomic and non-anatomic liver resection on early recurrence in patients with Hepatocellular Carcinoma

BackgroundFor Hepatocellular Carcinoma (HCC) treated with hepatectomy, the extent of the resection margin remains controversial and data available on its effect on early tumor recurrence are very few and contradictory. The purpose of this study was to compare the impact of the type of resection (anatomic versus non-anatomic) on early intra-hepatic HCC recurrence in patients with solitary HCC and preserved liver function.MethodsAmong 53 patients with similar clinico-pathologic data who underwent curative liver resection for HCC between 2000 and 2006, 28 patients underwent anatomic resection of at least one liver segment and 25 patients underwent limited resection with a margin of at least 1 cm.ResultsAfter a close follow-up period of 24 months, no difference was detected in recurrence rates between the anatomic (35.7%) and the non-anatomic (40%) groups in either univariate (p = 0.74) and multivariate (p = 0.65) analysis. Factors contributing to early recurrence were tumor size (p = 0.012) and tumor stage including vascular invasion (p = 0.009).ConclusionThe choice of the type of resection for HCC should be based on the maintenance of adequate hepatic reserve. The type of resection (anatomic vs non-anatomic) was found not to be a risk factor for early tumor recurrence.

A Case of Hepatocellular Carcinoma with Pulmonary Metastases Treated Successfully with a Combination of Repeated Hepatic Arterial Infusion Epirubicin and Cisplatin Chemotherapy and Systemic Low-Dose Infusion of 5-Fluorouracil

We report a case of hepatocellular carcinoma (HCC) with pulmonary metastases treated with repeated hepatic arterial infusion chemotherapy (HAIC) comprising epirubicin and cisplatin, and systemic infusion of 5-fluorouracil (a modified EC/F protocol), which led to complete remission. A 49-year-old man with compensated liver cirrhosis experienced intrahepatic recurrence of HCC with extensive lung metastases. The modified EC/F therapeutic protocol, which was applied at the tenth cycle every 4-5 weeks, resulted in disappearance of the pulmonary metastases and normalization of serum α-fetoprotein levels. A single small HCC lesion was found in the left lobe of the liver 13 months after the final chemotherapy session. HAIC with the same regimen was conducted again, followed by percutaneous intratumoral chemoinjection therapy with 5-fluorouracil and interferon-γ. Thereafter, there was no evidence of recurrence in either the liver or the lung, as evidenced by image analysis and expression of tumor markers. The disease-free intervals for the liver and lung were 41 and 54 months, respectively.

Complete Necrosis After Transarterial Chemoembolization Could Predict Prolonged Survival in Patients with Recurrent Intrahepatic Hepatocellular Carcinoma After Curative Resection

We explored the predictors of response to transarterial chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular carcinoma (HCC) after hepatectomy and investigated the survival of these patients according to the response to TACE. We analyzed data from 199 consecutive HCC patients who underwent curative liver resection and who later received repeat TACE for intrahepatic HCC recurrence. Of 199 patients, 139 (69.8%) achieved complete necrosis (CN) of HCC after repeated TACE (mean TACE session number, 1.3) and the other 60 (30.2%) (non-CN group) did not achieve CN. At hepatectomy, the CN group showed significantly smaller proportions of tumor capsular invasion, microvascular invasion, and pathologic tumor-node-metastasis stage III or IV HCCs. At first TACE, the CN group showed a significantly greater proportion of patients with time to recurrence > or = 1 year, Child-Pugh class A, serum alpha-fetoprotein (AFP) levels < 200 ng/mL, tumor size < 3 cm, solitary tumors, and nodular tumor types; portal vein invasion were less common than seen in the non-CN group. After multivariate analysis, tumor size < 3 cm and a single tumor at first TACE were independently related to attainment of CN after TACE. Median survival after first TACE was significantly longer in the CN group (48.9 versus 17.0 months). In a Cox regression model, CN after TACE was an independent predictor of favorable survival outcome after first TACE. CN after repeat TACE for postresection intrahepatic recurrence was attained more commonly in patients with smaller tumor size and lower tumor number at first TACE and favored longer survival in recurrent patients.

Tumor doubling time after initial response to transarterial chemoembolization in patients with hepatocellular carcinoma

Objective. Following initial transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC), these tumors can frequently recur, making it important to determine the appropriate follow-up interval after initial response to TACE. We therefore assessed the time taken by new recurrent HCCs to double in volume after an initial response to TACE. Material and methods. This retrospective cohort study included 73 patients who achieved an initial response after TACE. After intrahepatic distant recurrence of HCC, dynamic CT scans were reviewed by two radiologists without clinical information, and the doubling time of new recurrent nodules was determined. The relationship between doubling time and clinical factors was also analyzed. Results. In 32 of the 73 patients, 40 intrahepatic distant recurrent (IDR) nodules were detected over a median period of 14 months (range 4–46 months). The 1-, 2- and 3-year cumulative IDR rates of patients were 27%, 45% and 65%, respectively. The doubling time of IDR HCC ranged from 20 to 104 days, with a median of 46 days. Over 90% of IDR HCCs had a doubling time of less than 3 months. The doubling time (median 108 days; range 51–129 days) of primary HCC in five patients for whom we had information regarding primary tumors was longer than that of recurrent nodules (median 28 days; range 24–90 days) in the same five patients (P = 0.022). Conclusions. The median doubling time of IDR HCCs after an initial response was 47 days (range 20–104 days). These findings indicate that the appropriate follow-up interval for dynamic CT in patients with an initial response after TACE is less than 3 months.

The value of anatomical liver sectionectomy for patients with a solitary hepatocellular carcinoma from 2 to 5 cm in greatest diameter

The value of anatomical liver sectionectomy for patients with a solitary hepatocellular carcinoma (HCC) from 2 to 5 cm in greatest diameter has not been clarified. We retrospectively studied 454 patients with a solitary HCC from 2 to 5 cm in greatest diameter who underwent initial curative hepatectomy from 1991 to 2006. We separated the liver into three segments according to the Glissonean pedicle ramification (Takasaki's liver segments). Takasaki's segment is recognized as a section in the International Hepato-Pancreato-Biliary Association Brisbane 2000 terminology. Outcomes after sectionectomy (n = 143) and partial sectionectomy (n = 311) for patients with a solitary HCC from 2 to 5 cm in greatest diameter were examined. The 5-year recurrence-free survival rate and survival rate after sectionectomy (42% and 81%, respectively) were significantly better than those after partial sectionectomy (27%: P = 0.0023, and 66%: P = 0.0006, respectively). Multivariate analysis showed sectionectomy to be a significant independent prognostic factor for recurrence-free survival and overall survival in patients with a solitary HCC from 2 to 5 cm in greatest diameter (P = 0.0217, and P = 0.0085, respectively). Anatomical liver sectionectomy prevents intrahepatic recurrence of HCC and prolongs survival in patients with a solitary HCC from 2 to 5 cm.

Prognostic impact of treatment modalities on patients with single nodular recurrence of hepatocellular carcinoma

To evaluate the prognostic impact of various therapeutic modalities, such as repeat hepatectomy, ablation therapy, and transcatheter arterial chemoembolization (TACE) therapy, used to treat single nodular recurrent hepatocellular carcinoma (HCC). Thirty-two patients with single nodular intrahepatic recurrence after curative primary resection of HCC were enrolled in this study. The prognostic factors after recurrence were established using 13 clinicopathologic variables, including the therapeutic modalities; namely, repeat hepatectomy, ablation therapy, or TACE therapy. Of the 32 patients, 9 underwent repeat hepatectomy, 10 underwent ablation therapy, and 13 underwent TACE therapy. The therapeutic modality was the only prognostic factor. In comparison with TACE therapy, the relative risks associated with ablation therapy and repeat hepatectomy were 0.19 and 0.29, respectively. The 5-year survival rates after single nodular recurrence were 57% in the ablation therapy group, 29% in the repeat hepatectomy group, and 0% in the TACE therapy group. Repeat hepatectomy and ablation therapy are more effective than TACE therapy for improving the prognosis of patients with single nodular intrahepatic recurrent HCC.

Combination of peritumoral mast cells and T‐regulatory cells predicts prognosis of hepatocellular carcinoma

The peritumoral inflammatory environment is critical for the progression of intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resections. Here, we investigated the relevance of peritumoral mast cells (MCs) to HCC outcomes. Peritumoral tryptase(+) MCs in addition to Foxp3(+) T-regulatory cells (Tregs) were evaluated using immunohistochemistry enumeration in tissue microarrays containing 207 randomly selected HCC patients. Clinicopathological factors and postoperative outcomes were compared between high and low subgroups of MCs or Tregs. Compared to low denstiy, higher peritumoral MCs were associated with poorer clinical outcomes, and independently related to elevated 5-year recurrence incidence (54.1%vs 39.2%, P = 0.026). High-dense MCs were especially related to increased probability of early recurrence (within 2 years) (P = 0.004). We also found that peritumoral Tregs were positively correlated with MCs in density (r = 0.353, P < 0.001) and reversely related to HCC outcomes. Notably, MCs in combination with Tregs displayed better prognostic performances than MCs alone (area under curve [AUC](survival) = 0.629 vs 0.589, AUC(recurrence) = 0.632 vs 0.591). Moreover, MCs were positively correlated to alanine aminotransferase, a serum inflammatory marker (P = 0.014). Therefore, peritumoral MCs are promising prognostic parameters for HCC mainly through inflammation response-related mechanisms, and we propose that MCs and Tregs may cooperate with each other and result in poorer prognosis.

Preoperative Radiologic and Postoperative Pathologic Risk Factors for Early Intra-Hepatic Recurrence in Hepatocellular Carcinoma Patients Who Underwent Curative Resection

PurposeThe risk of hepatocellular carcinoma (HCC) recurrence must be considered ahead of surgery. This study was undertaken to identify pre-operative risk factors for early intrahepatic recurrence of HCC after curative resection in a large-scale.Materials and MethodsWe retrospectively reviewed the preoperative three-phase multi-detector CT (MDCT) and laboratory data for 240 HCC patients who underwent curative resection; tumor size, number, gross shape, capsule integrity, distinctiveness of tumor margin, portal vein thrombosis (PVT), alpha-fetoprotein level (AFP), and protein induced by vitamin K absence-II (PIVKA-II) levels were assessed. Surgical pathology was reviewed; tumor differentiation, capsule, necrosis, and micro-vessel invasion were recorded.ResultsHCC recurred in 61 patients within six months (early recurrence group), but not in 179 patients (control group). In univariate analysis, large tumor size (p = 0.018), shape (p = 0.028), poor capsule integrity (p = 0.046), elevated AFP (p = 0.015), and PIVKA-II (p = 0.008) were significant preoperative risk factors. Among the pathologic features, PVT (p = 0.023), Glisson's capsule penetration (p = 0.033), microvascular invasion (p < 0.001), and poor differentiation (p = 0.001) showed statistical significance. In multivariate analysis, only the histopathologic parameters of microvascular invasion and poor differentiation achieved statistical significance.ConclusionPreoperative CT and laboratory parameters showed limited value, while the presence of microscopic vascular tumor invasion and poorly differentiated HCC correlated with higher risk of early recurrence after curative resection.

Re-evaluation of lipiodolized transarterial chemoembolization therapy for intrahepatic recurrence of hepatocellular carcinoma after curative liver resection

While lipiodolized transarterial chemoembolization (lip-TACE) is effective for treating unresectable hepatocellular carcinoma (HCC), its effect for treating recurrent HCC after curative liver resection needs to be clarified. Of 163 patients who had undergone curative liver resection between 1992 and December 2003, 65 patients (39.8%) had recurrent HCC in the liver without extrahepatic recurrence and were indicated for lip-TACE. The overall survival rate after lip-TACE was calculated, and its correlation with factors such as the histology of the primary HCC and background noncancerous tissue were analyzed. The overall survival rates after lip-TACE after the detection of the first recurrent HCC were 82.6%, 44.5%, and 24.8% at 1, 3, and 5 years, respectively. The factors affecting patient survival after lip-TACE were microscopic portal venous involvement of HCC at liver resection, grade of inflammation in the noncancerous liver parenchyma, and recurrence within 1 year after the initial liver resection. Multivariate analysis showed that the period between the resection and first recurrence had the highest hazard ratio. Lip-TACE is a reasonable procedure for treating recurrent HCC in selected patients who are not eligible for hepatic re-resection. When HCC recurred within 1 year from the primary liver resection, the effect of lip-TACE on patient survival was limited.

Elevated Perioperative Transaminase Level Predicts Intrahepatic Recurrence in Hepatitis B-related Hepatocellular Carcinoma After Curative Hepatectomy

We aimed to evaluate the role of elevated perioperative alanine aminotransferase (ALT) as a surrogate marker of hepatitis activity in determining the risk of recurrence and survival in hepatitis B-related hepatocellular carcinoma (HCC) after curative hepatectomy. A retrospective review of the hepatectomy database was performed and 142 patients were found who had hepatitis B-related HCC from January 2001 to March 2006. Their ALT levels preoperatively and 1 month, 3 months, and 6 months postoperatively were recorded. The risk factors for recurrence and prognostic factors of survival were analysed. An elevated perioperative ALT level (p = 0.021), multiple tumour nodules in the resected specimen (p < 0.001), and a tumour size greater than 5 cm (p = 0.001) were significant independent risk factors for tumour recurrence. The latter two factors were also independent prognostic factors for overall survival and disease-free survival. An elevated ALT level was an independent prognostic factor for disease-free survival (p = 0.025). An elevated perioperative ALT level, which reflects increased hepatitis activity, is an independent risk factor for intrahepatic recurrence of hepatitis B-related HCC. It is also associated with a poorer disease-free survival rate.

A three-gene predictor for early intrahepatic recurrence of hepatocellular carcinoma after curative hepatectomy

We previously developed a DNA microarray-based system that out-performs traditionally used clinical parameters for prediction of early intrahepatic recurrence (IHR) of hepatocellular carcinoma (HCC). Because DNA microarray is too expensive for daily clinical use, we used a quantitative real-time reverse transcription-polymerase chain reaction (QRT-PCR) to develop a lower-cost predictor for early IHR. From the 12 early IHR-related genes integrated in the previous predictor, we selected 6 genes whose levels showed the strongest association between data from the 2 distinct DNA microarray platforms with the same sample set. Expression of these 6 genes relative to that of GAPDH was measured by QRT-PCR in 82 HCCs. Of the 82 HCCs, 39 and 43 were assigned to training and independent test sets, respectively. By searching all combinations (n=2-6) of the 6 genes, we found an optimal combination of 3 genes (HLADRA, DDX17 and LAPTM5) that minimized the leave-one-out error for prediction of early IHR in the training set. The 3-gene predictor constructed with the Fisher linear classifier correctly predicted early IHR or non-recurrence in 35 (81.4%) of 43 HCCs in the independent test set and had a high positive predictive value of 72.7% and a high negative predictive value of 84.4%. Multivariate analysis with the stepwise logistic regression showed that the 3-gene predictor [F(x)<0] was an independent risk factor for early IHR (risk ratio, 13.6; p=0.006), indicating its potential as an easy-to-use predictor for accurate prediction of early IHR of HCC.

Intrahepatic distant recurrence after radiofrequency ablation for a single small hepatocellular carcinoma: Risk factors and patterns

The pathogenesis of frequent intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection or local ablation therapy remains uncertain. Risks and patterns of intrahepatic distant recurrence (IDR) of a single, primary HCC lesion after radiofrequency (RF) ablation were examined. Ninety patients with a single primary HCC lesion of less than 3 cm who had complete RF ablation were enrolled in the study. Risk factors for IDR and the patterns of IDR after RF ablation were analyzed. The median follow-up was 37.4 months. IDR was observed in 44 (48.9%) patients. The cumulative rate of IDR was 10.4%, 52.5%, and 77.0% at 1, 3, and 5 years, respectively. Univariate analysis revealed that a pretreatment serum alpha-fetoprotein (AFP) level of > or =50 ng/ml (P = 0.0324), a des-gamma-carboxy prothrombin (DCP) level of > or =40 mAu/ml (P = 0.006), an ablative margin of <5 mm of the ablation zone (P = 0.0306), and a prothrombin time of <70% (P = 0.0188) were related to IDR. A multivariate stepwise Cox proportional hazards regression model revealed that pretreatment serum AFP and DCP level and the ablative margin were independent risk factors for IDR pretreatment. Serum DCP level > or = 40 mAu/ml (P = 0.025), local tumor progression (P = 0.011), and ablative margin < 5 mm (P = 0.024) were related to multiple IDR. HCC patients with high serum AFP or DCP before RF ablation should be carefully followed up to monitor any IDR. A sufficient ablative margin in RF ablation for HCC is required to prevent IDR.

Survival Analysis of Patients With Transplantable Recurrent Hepatocellular Carcinoma

There is no difference in the survival benefit between salvage liver transplant and nontransplant therapies for recurrent hepatocellular carcinoma (HCC). Retrospective study. Tertiary referral center. Sixty patients developed transplantable intrahepatic recurrent HCC after curative resection. Twelve patients received salvage liver transplant, whereas 48 received nontransplant therapies, including a second surgical resection, radiofrequency ablation, transarterial chemoembolization, and percutaneous ethanol injection. The overall survival rates were compared between the 2 groups. Clinicopathologic variables were evaluated by univariate and multivariate analyses for their influence on overall survival. There was no significant difference in overall survival rates between the salvage transplant and nontransplant groups. In the nontransplant group, pTNM (pathologic TNM) staging at primary resection and the time from primary resection to tumor recurrence were identified as independent prognostic factors affecting overall survival. These 2 factors carried no prognostic value in the salvage transplant group. Patients in the salvage transplant group with stage II tumors before the primary resection or intrahepatic recurrence within 12 months of the primary resection had significantly better overall survival than did the nontransplant group with corresponding poor prognostic factors. Patients with transplantable intrahepatic recurrence can be treated effectively by salvage transplant or nontransplant therapies. Salvage transplant may be more beneficial to patients with stage II tumors before the primary resection and those with early intrahepatic recurrence.

Multi-organ Early Tumor Dissemination After High Urgency Re-transplantation for Hepatocellular Carcinoma in Cirrhosis: Role of Massive Intraoperative Transfusion?

The recurrence rate of hepatocellular carcinoma (HCC) after liver transplantation (LT) ranges between 11 and 18% [1, 2]. Although the role of post-transplant immunosuppression is still unclear [3, 4], most recurrences seem to be related to malignant cells present but not identified at the time of transplantation and/or released during the transplant procedure. Patients whose explanted liver tumors are within currently accepted criteria for transplantation have a low rate of recurrence [5]. While partial tumor necrosis after performance of bridging treatments could result in earlier tumor recurrence post-transplant [6], 100% tumor necrosis is usually associated with very good results [7]. We report on a patient with unexpected multi-organ early tumor dissemination after an initial LT for a complete necrotic HCC in the setting of cirrhosis and a subsequent high urgency re-transplantation for primary non-function. The patient is a 55-year-old man with chronic hepatitis Binduced liver cirrhosis, Child-Turcotte-Pugh class A, and a solitary recurrent HCC meeting the Milan criteria in Segments VI/VIII. The patient had undergone a partial Segment VII resection in December 2003 for a solitary HCC (pT1 G1 V0). Follow-up examinations proved a local recurrence in Segment VI/VIII in January 2005. Further diagnostic workup (abdominal and thoracic computed tomography, bone scintigraphy, positron emission tomography) excluded further tumor manifestations. The patient was evaluated for LT and listed in ‘‘Eurotransplant’’. A computed tomography (CT)-guided radiofrequency ablation was performed for the 4.8 · 3.4 cm HCC in January 2005. Further follow-up studies with CT, magnetic resonance imaging, and positron emissions tomography (PET)-CT showed complete necrosis of the lesion. After a waiting time of 127 days, the patient received a deceased donor full-size liver graft. The last imaging studies were a magnetic resonance imaging and whole-body PET-CT 2 months prior to LT, showing a necrotic area in the ablated liver segment as well as no further malignancy. Intraoperative mismanagement of inferior vena cava and central venous pressure led to excessive bleeding and corresponding transfusion of 46 units of packed red blood cells, plasma, and coagulation factors. Pathological examination of the explanted liver showed 100% necrosis of the HCC lesion as well as no viable tumor in the setting of end-staged liver cirrhosis. The patient experienced primary graft non-function leading to multiorgan failure, and was re-listed as ‘‘high-urgency’’. Three days later he underwent an uneventful re-LT. Neither of the donors had any history or physical evidence of malignancy. After discharge, the patient was followed up at our outpatient liver transplant clinic. The first HCC imaging follow-up at 4 months post-transplant with abdominal and thoracic CT showed no evidence of HCC recurrence. The second HCC follow-up at 8 months post-transplant showed multifocal bilobar intrahepatic HCC recurrence, intraabdominal involved lymph nodes, and multiple bilateral pulmonary and axillary lymph nodes metastases. Percutaneous liver biopsy confirmed the diagnosis of HCC recurrence. Immunosuppression was switched to rapamycin. The patient opted to receive palliative chemotherapy, fully aware of its limited efficacy, and he died 21 months post-transplant. Although the tumor was a well-differentiated HCC without vascular invasion, radiofrequency ablation resulted G. C. Sotiropoulos (&) S. Beckebaum E. P. Molmenti C. G. Klein V. R. Cicinnati C. E. Broelsch M. Malago Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany e-mail: georgios.sotiropoulos@uni-essen.de

Sectionectomy Is Suitable for Patients with T2 Hepatocellular Carcinoma according to the Modified International Union against Cancer TNM Classification

Background/Aims: The effectiveness of systematized hepatectomy in the modified International Union Against Cancer (UICC) staging classification for hepatocellular carcinoma (HCC) has not been clarified in detail. Methods: We retrospectively studied 406 patients with UICC T1 HCC and 124 patients with T2 HCC who underwent initial curative hepatectomy from 1994 through 2003. Outcomes after sectionectomy or larger resection and segmentectomy or smaller resection for patients with T1 HCC and T2 HCC were examined. Results: The overall recurrence-free survival rate and survival rate of sectionectomy or larger resection at 5 years (45 and 79%, respectively) did not significantly differ from those of segmentectomy or smaller resection (38 and 81%, respectively) in patients with T1 HCC. However, in patients with T2 HCC, the 5-year recurrence-free survival rate and survival rate after sectionectomy or larger resection (37 and 71%, respectively) were significantly different from those after segmentectomy or smaller resection (6%: p < 0.0001, and 35%: p = 0.0027, respectively). Multivariate analysis showed sectionectomy or larger resection to be a significant independent prognostic factor for recurrence-free survival and survival in patients with T2 HCC. Conclusions: Sectionectomy or larger resection prevents intrahepatic recurrence of HCC and prolongs survival in patients with T2 HCC.

Percutaneous Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma After Hepatectomy: Long-term Results and Prognostic Factors

We evaluated the long-term survival results and safety of percutaneous radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) after hepatectomy, and assessed the prognostic factors that can influence its long-term therapeutic results. One hundred and two patients, who had 119 recurrent HCC in their livers, underwent ultrasound-guided percutaneous RFA. All the patients had a history of hepatic resection as a first-line treatment modality for HCC. The mean diameter of the recurrent tumors was 2.0 cm (range, 0.8-5.0 cm). We evaluated the effectiveness rates, local tumor progression rates, survival rates, and complications. We also assessed the prognostic factors of the survival rates by using Cox proportional hazard models. The primary effectiveness rate was 93.3% (111 of 119). The cumulative rates of local tumor progression at 1, 3, and 5 years were 6.0, 8.6, and 11.9%, respectively. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 93.9, 83.7, 65.7, 56.6, and 51.6%, respectively. Patients with a lower serum alpha-fetoprotein (AFP) level (<or=100 microg/L) before RFA or with small resected tumors (<or=5 cm) demonstrated better survival results (P < .05). There was only one major complication (liver abscess, 1.0% per treatment) during the follow-up period. There were no procedure-related deaths. Percutaneous RFA is an effective and safe treatment modality for intrahepatic recurrent HCC after hepatectomy. Serum AFP level before RFA and resected tumor size were significant prognostic predictors of long-term survival.