Comparison of Combined Hepatocellular and Cholangiocarcinoma with Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

Purpose Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary hepatic neoplasm (PHN) with features of both hepatocellular and biliary differentiation. We compared the outcome of hepatic resection in patients with HCC-CC, those with hepatocelluar carcinoma (HCC), and those with cholangiocarcinoma (ICC). Methods Between November 1994 and December 2003, 952 patients underwent hepatic resection for a PHN. Results The incidence of HCC-CC was 3.5%. Hepatitis B surface antigen was positive in 51.2% of these patients and the HCV antibody was positive in 12.2%. Positive hepatitis serology was more common in the HCC group (66.7%). The prevalence of underlying liver cirrhosis was significantly lower in the ICC group (7.8%) than in the HCC (49%) and HCC-CC (41.5%) groups (P < 0.0001). The median overall survival periods after hepatic resection of HCC-CC, HCC, and ICC were 47.3, 71.7, and 21.5 months, respectively (P < 0.0001). The median disease-free survival (DFS) periods after hepatic resection for HCC-CC, HCC, and ICC were 23.4, 68.2, and 15.5 months, respectively (P < 0.0001). Conclusion Patients with transitional type HCC-CC had significantly poorer survival rates than those with HCC, after hepatic resection. Therefore, a more aggressive treatment modality should be explored to improve the survival rate of these patients.     

Long-Term Outcome of Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma

Purpose

Combined hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) is a rare pair of intrahepatic malignancies. Differential diagnosis among combined HCC-CCC, HCC, or CCC can be difficult; thus malignancies other than ordinary HCC are occasionally encountered unexpectedly in explanted liver specimens. The present study analyzed the long-term outcomes of liver transplantation (OLT) among patients with HCC-CCC.

Methods

Between January 1999 and December 2009, we performed 2137 adult OLT at our institution including 15 cases of pathologically confirmed HCC-CCC, who all underwent OLT with a pretransplant diagnosis of HCC. We reviewed retrospectively the medical records of these 15 patients.

Results

Their mean age was 58.9 ± 7.2 years. The median preoperative alpha-fetoprotein level was 32.6 ng/mL. Fourteen patients underwent living donor and one deceased donor OLT. The Milan criteria were met in 12 cases. A single tumor was identified in 8 and multiple lesions in 7 patients. The maximal tumor diameter was 2.9 ± 1.7 cm. Seven patients experienced tumor recurrences: including 6 within the first 12 months. All of the patients who experienced recurrences died at a median 4 months after that diagnosis. The overall patient survival rates were 66.7% at 1 year and 60.0% at 3 and 5 years. Disease-free patient survival rates were 60.0% at 1 year and 53.3% at 3 and 5 years.

Conclusions

Patients with combined HCC-CCC showed a high rate of early recurrences, particularly within the first year.     

Hepatocellular Carcinoma: Resection or Transplantation

  This paper was originally presented as part of an SSAT Controversies in GI Surgery debate entitled, “Hepatocellular Carcinoma in the Mild Cirrhotic: Transplant or Resect?”, at the SSAT 49th Annual Meeting, May 2008, in San Diego, CA, USA. The other article presented in the debate was Pawlik TM, Resection for Early Hepatocellular Carcinoma.     

Comparison Between Salvage Liver Transplantation and Repeat Liver Resection for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-analysis

Introduction

Repeat liver resection (RLR) has been adopted by surgeons as the first-line treatment in the case of intrahepatic recurrence of hepatocellular carcinoma (HCC), whereas salvage liver transplantation (SLT) is considered a second-line option. The aim of our study was to evaluate the results of SLT and RLR for HCC.

联合血管切除及重建在进展期肝门部胆管癌切除中的应用

对肝胆外科医生而言,肝门部胆管癌仍然是目前最困难的挑战:肝十二指肠韧带处解剖复杂,胆管分叉与入肝血管过于接近,往往难以获得阴性的外科切缘.我们在临床中对肝门部胆管癌进行切除时发现,有近80%的患者存在血管侵犯,以门静脉侵犯多见,且有些同时伴有肝动脉侵犯.     

Liver Transplantation and Liver Resection for Cirrhotic Patients with Hepatocellular Carcinoma: Comparison of Long-Term Survivals

Background

Both liver transplantation (LT) and liver resection (LR) represent curative treatment options for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. In this study, we have compared outcomes between historical and more recent patient cohorts scheduled either for LT or LR, respectively.

Methods

Clinicopathological data of all patients with HCC and cirrhosis who underwent LT or LR between 1989 and 2011 were evaluated. Overall survival of patients with HCC within the Milan criteria (MC) was analyzed focusing on changes between different time periods.

Results

In total, 364 and 141 patients underwent LT and LR for HCC in cirrhosis, respectively. Among patients with HCC within MC, 214 and 59 underwent LT and LR, respectively. Postoperative morbidity (37 vs. 11%, P?<?.0001), but not mortality (3 vs. 1%, P?=?.165), was higher after LR than after LT for HCC within MC. In the period 1989–2004, overall survival (OS) was significantly higher in patients who underwent LT compared to LR for HCC within MC (5-year OS: 77 vs. 36%, P?<?.0001). Interestingly, in the more recent period 2005–2011, OS was comparable between LT and LR for HCC within MC (5-year OS: 73 vs. 61%, P?=?.07).

Conclusion

We have noted an improvement of outcomes among patients selected for partial hepatectomy in recent years that were comparable to stable results after LT in cirrhotic patients with HCC. Whether those improvements are due to advances in liver surgery, optimized perioperative managament for patients with liver cirrhosis, and the development of modern multimodal treatment strategies for the recurrent lesions appears plausible.

     

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.

Surgical Treatments and Prognoses of Patients with Combined Hepatocellular Carcinoma and Cholangiocarcinoma

Background  Combined hepatocellular carcinoma and cholangiocarcinoma is a very rare form of primary liver cancer containing components of both tumor types. We evaluated the effectiveness of surgical treatment and factors related to survival and recurrence. Patients and Methods  Of the 2427 patients who underwent hepatectomy or liver transplantation because of a primary hepatic malignancy from January 1989 to July 2006 at the Asan Medical Center, Seoul, Korea, 29 had hepatocellular carcinoma and cholangiocarcinoma as a single mixed or transitional tumor. Their medical records were retrospectively reviewed. Results  Disease-free survival rates at 6 months, 1 year, and 3 years were 51.1%, 38.3%, and 25.6%, respectively. Univariate analysis showed that CA 19–9 above 37 U/ml was predictive of low overall survival (P = .03) and that TNM stage was significantly associated with disease-free survival (P = .04). Conclusions  Patients with combined hepatocellular carcinoma and cholangiocarcinoma had poor postoperative survival rates. High CA 19–9 level was associated with poorer survival, suggesting that the cholangiocarcinoma portion may be a major determining factor for patient prognosis. Aggressive surgical treatment, including lymph node dissection, may improve survival in patients suspected of or diagnosed with these tumors.     

Resection of Pulmonary Metastases from Hepatocellular Carcinoma following Liver Transplantation

Background

This study was intended to assess the effect of resection of pulmonary metastasis (PM) of hepatocellular carcinoma (HCC) after liver transplantation (LT). No effective treatment modality exists for PM-HCC, and little is known about the posttransplant outcomes of pulmonary metastasectomy (PMT).

Methods

Of 587 adult LT recipients diagnosed with HCC, 43 had PM-HCC. We retrospectively compared outcomes in 23 patients who underwent PMT and 20 who did not. PMT was precluded in ten patients in the non-PMT group by multiple (usually ≥5) lung nodules, in nine by lung nodules with concurrent or residual extrapulmonary metastasis, and in one by comorbidity.

Results

Of the 23 patients in the PMT group, 14 underwent a single session of PMT, 7 underwent 2 sessions each, and 2 underwent 3 sessions each, for a total of 34 sessions. There were no surgery-related deaths or complications. After first PMT, 41 nodules, each 0.2–2.5 cm in diameter, were observed: 1–5 nodules per patient. Every available treatment was provided to patients with post-PMT recurrence and those in the non-PMT group to control pulmonary and extrapulmonary metastases. Patient survival rates before PM diagnosis did not differ between the two groups (p?=?0.141). However, 2?year post-PM survival rate was significantly greater in the PMT group (30.6% vs. 0%, p?=?0.007), resulting in a significantly greater overall 5?year survival rate (44.7% vs. 12.8%, p?=?0.017). Univariate analysis showed no risk factor significantly associated with patient survival after PMT.

Conclusions

PMT should be performed for resectable PM-HCC because it may provide a chance of long-term survival.     

The Predictive Value of Staging Systems and Inflammation Scores for Patients with Combined Hepatocellular Cholangiocarcinoma After Surgical Resection: a Retrospective Study

Background

Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare form of primary liver tumor. A specific staging system for predicting survival in patients with cHCC-CC is not available. The aim of the present study was to evaluate the ability of staging systems and inflammation-based scores to predict overall survival (OS) and progression-free survival (PFS) of patients with cHCC-CC after surgical resection.

Methods

The data from 99 patients with cHCC-CC after surgical resection from June 2000 and January 2017 were retrospectively collected. Patients were allocated into HCC (hepatocellular carcinoma)—dominant (IHD) group and ICC (intrahepatic cholangiocarcinoma)—dominant (IID) group based on radiological characteristics. Similarly, patients were also divided into HCC-dominant (PHD) group and ICC-dominant (PID) group based on pathological characteristics. Univariate and multivariate analyses were performed to identify variables associated with OS and PFS. The prognostic value of staging systems and inflammation-based scores were analyzed and compared using receiver operating characteristic (ROC) curves.

Results

The 1-, 2-, and 3-year OS rates were 82.6, 66.3, and 59.6%, respectively. The 1-, 2-, and 3-year PFS rates were 52.2, 38.1, and 31.5%, respectively. Independent prognostic factors identified by multivariate analyses included HCC-TNM staging system and tumor diameter both for OS and PFS analyses. HCC-TNM staging system displayed higher area under ROC curve (AUC) values than the other staging systems or inflammation-based scores.

Conclusions

HCC-TNM staging system was able to adequately predict prognosis of patients with cHCC-CC after surgical resection, especially for patients with HCC-dominant characteristics in clinical practice.

     

Resection of Hilar Cholangiocarcinoma

Objective: Morbidity and mortality involved in the resection of hilar cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and laboratory parameters that might influence the patient''s survival also were re-evaluated.Summary Background Data: Although much progress has been made in the diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most patients remains poor. Surgical resection is usually prohibited because of its local invasiveness, and most patients can only be managed by palliative drainage. Recently, many surgeons have adopted a more aggressive resection with varying degrees of success. Several prognostic factors in bile duct carcinoma have been proposed; however, no reports have specifically focused on resected hilar cholangiocarcinoma and its prognostic survival factors using multivariate analysis.Methods: The clinical records and pathologic slides of 49 cases with resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical and laboratory parameters were evaluated for their correlation with postoperative morbidity and mortality, whereas 31 variables were evaluated for their significance with postoperative survival. Variables showing statistical significance in the first univariate analysis were included in the following multivariate analysis using stepwise logistic regression test for factors affecting morbidity and mortality and Cox stepwise proportional hazard model for factors influencing survival.Results: There were 5 in-hospital deaths, and the cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a median survival of 14.0 months. Multivariate analysis disclosed that coexistent hepatolithiasis and lower serum asparate aminotransferase levels (90 U/L) had a significant low incidence of postoperative morbidity, whereas a serum albumin of less than 3 g/dL was the only significant factor affecting mortality. Regarding survival, univariate analysis identified eight significant factors: 1) total bilirubin 10 mg/dL, 2) curative resection, 3) histologic type, 4) perineural invasion, 5) liver invasion, 6) depth of cancer invasion, 7) positive proximal resected margin, and 8) positive surgical margin. However, multivariate analysis disclosed total bilirubin ≥ 10 mg/dL, curative resection, and histologic type as the three most significant independent variables.Conclusions: Surgical resection provides the best survival for bilar cholangiocarcinoma. An adequate nutritional support to increase serum albumin over 3g/dL is the most important factor to decrease postoperative mortality. Moreover, preoperative biliary drainage to decrease jaundice and a curative resection with adequate surgical margin are recommended if longer survival is anticipated. Patients with well differentiated adenocarcinoma seem to survive longer compared to those with moderately or poorly differentiated tumors.     

Surgical Management of Early-Stage Hepatocellular Carcinoma: Resection or Transplantation?

Background  The surgical management of hepatocellular carcinoma in patients with well-compensated cirrhosis is controversial. The purpose of the current study was to compare the outcome of patients with well-compensated cirrhosis and early stage hepatocellular carcinoma treated with initial hepatic resection versus transplantation. Methods  Between 1985 and 2008, 245 patients underwent hepatic resection, and 134 patients underwent liver transplantation for early stage hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic factors were evaluated using univariate and multivariate analyses; survival was calculated using the Kaplan–Meier method. Results  Compared with transplantation, patients undergoing resection had larger tumors and a higher incidence of microscopic vascular invasion. Transplantation was associated with better 5-year disease-free and overall survival compared with resection. Hepatitis status, presence of microscopic vascular invasion, and tumor size were predictors for recurrence, while the presence of microscopic vascular invasion and tumor size conferred an increased risk of death. The disease-free survival advantage with transplantation was more pronounced in hepatitis C patients compared with non-hepatitis and hepatitis B patients. The overall survival advantage with transplantation persisted in cases of solitary lesions ≤3 cm, but was attenuated in patients with a MELD score ≤ 8. Conclusion  In well-compensated cirrhotic patients with early stage hepatocellular carcinoma, transplantation was associated with longer disease-free and overall survival. Patients undergoing resection did, however, have tumors with more advanced pathologic features. Patients best suited for initial resection as the treatment of hepatocellular carcinoma were those with a MELD score ≤ 8 without evidence of hepatitis. Presented at the 49th Annual Meeting of The Society for Surgery of the Alimentary Tract, May 18, 2008, San Diego, CA, USA.     

Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma

BackgroundScarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT) for localized hepatocellular carcinoma (HCC) patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC.MethodBetween January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38) vs OLT (n = 28) for localized HCC were compared using a prospectively maintained database.ResultsA total of 66 patients (with a median age of 62) who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P = .45) and perioperative mortality rates (7.9% vs 10.7%, P = .2) were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P = .0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P = .0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P = .034).However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P = .63). Based on logistic regression analysis, number of tumors (P = .034, odds ratio: 2.1) and “resection”-type surgery (P = .008, odds ratio: 20.2) were independently associated with recurrence.ConclusionCompared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality.     

Management of Lymph Nodes During Resection of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: A Systematic Review

The role of lymph node dissection (LND) in the treatment of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to systematically review all available evidence to determine the role of LND in patients with HCC and ICC. Studies that reported on LND, lymph node metastasis (LNM), and short- and long-term outcomes for patients with HCC or ICC survival were identified from PubMed, Cochrane, Embase, Scopus, and Web of Science databases. Data were extracted, synthesized, and analyzed using standard techniques. A total of 603 and 434 references were identified for HCC and ICC, respectively. Among HCC patients, the overall prevalence of LND was 51.6 % (95 % confidence interval (CI) 19.7-83.5) with an associated LNM incidence of 44.5 % (95 % CI 27.4–61.7). LNM was associated with a 3- and 5-year survival of 27.5 and 20.8 %, respectively. Among ICC patients, most patients 78.5 % (95 % CI 76.2–80.7) underwent LND; 45.2 % (95 % CI 39.2–51.2) had LNM. Three and 5-year survival among ICC patients with LNM was 0.2 % (95 % CI 0–0.7) and 0 %, respectively. While there are insufficient data to recommend a routine LND in all patients with HCC or ICC, the potential prognostic value of LND suggests that LND should at least be considered at the time of surgery.     

Harm and Benefits of Primary Liver Resection and Salvage Transplantation for Hepatocellular Carcinoma

Primary transplantation offers longer life‐expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting‐list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life‐expectancy in comparison to HR and salvage transplantation if 5‐year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time‐to‐transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting‐list population from re‐allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time‐to‐transplant could lead to a benefit for waiting‐list patients that outweighs this harm.     

Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Clinical Features, Treatment Modalities, and Prognosis

Background

Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary liver cancer that has rarely been reported in large-scale clinical studies. The aim of this study was to clarify the clinical features, treatment modalities, and prognosis of cHCC-CC.

Methods

Included in this study were 113 patients who were histologically diagnosed as having Allen type C cHCC-CC, 103 of whom received liver resection, 6 transarterial chemoembolization treatment, 3 radiofrequency ablation, and 1 palliative supportive treatment. Clinicopathologic features and prognosis of 103 cHCC-CC patients after liver resection were compared with those of 6,679 patients with hepatocellular carcinoma (HCC) and 386 patients with intrahepatic cholangiocarcinoma (ICC) who underwent liver resection during the same period.

Results

The proportion of cHCC-CC in primary liver cancers was 1.5?%. The 103 cases of cHCC-CC were characterized by male predominance, infection with hepatitis virus or presence of liver cirrhosis, and elevated alfa-fetoprotein??findings similar to HCC. However, serum CA19-9 elevation, incomplete capsules, and lymph node involvement were similar to ICC. The 1-, 3-, and 5-year overall survival rates after liver resection were 73.9, 41.4, and 36.4?%, respectively, for patients with cHCC-CC versus 77.5, 53.3, and 41.4?% for HCC patients, and 58.0, 29.1, and 22.3?% for ICC patients (??²?=?137.5, P?P?=?0.003) and radical liver resection (hazard ratio 0.31, 95?% confidence interval 0.14?C0.68, P?=?0.004) were independent prognostic factors for overall survival.

Conclusions

cHCC-CC has biological behavior and prognosis that are intermediate between HCC and ICC. Radical liver resection can provide a better outcome for this uncommon malignancy.     

Survival Benefit of Transplantation for Recurrence of Hepatocellular Carcinoma After Liver Resection

Background

Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non–transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies.

Methods

We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list.

Results

The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P = .84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P = .3), whereas 5-year ITT survival of DW patients was significantly higher (P < .01) than that of 105 beyond-Milan HCC patients resected only.

Conclusions

LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group.     

Long-Term Outcomes After Resection Versus Transplantation for Hepatocellular Carcinoma Within UCSF Criteria

Purpose  

We compared the long-term outcomes of resection and transplantation for hepatocellular carcinoma (HCC) while satisfying the University of California at San Francisco criteria.     

The Diagnostic Conundrum and Liver Transplantation Outcome for Combined Hepatocellular‐Cholangiocarcinoma

Combined hepatocellular‐cholangiocarcinoma (cHCC‐CC) is a rare primary liver malignancy with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) histological features. It is almost impossible to obtain an accurate, preoperative noninvasive diagnosis of cHCC‐CC with tumor markers or cross‐sectional abdominal imaging due to the mixed histological features. Despite these difficulties, accurate cHCC‐CC diagnosis remains an important goal with prognostic significance. In our study, we retrospectively reviewed the tumor markers: AFP and CA 19‐9, and cross‐sectional liver imaging, in light of liver explant findings, to identify and characterize cHCC‐CC features followed by liver transplantation (LT) outcome analysis. The results from this 12 patient cohort failed to identify characteristic features for cHCC‐CC. None of the imaging features helped to identify the cHCC‐CC tumor and they mimicked either HCC or CC, depending on the degree of glandular differentiation expressed histologically. In our cHCC‐CC LT recipients, the 1‐, 3‐ and 5‐year cumulative survival probabilities were 79%, 66% and 16%, respectively with a 5‐year survival comparable to or better than LT for intrahepatic CC but poorer than LT for HCC following the Milan criteria. Conceivably explained by its cholangiocarcinoma component the LT outcome for this rare and hard to diagnose tumor appears poor.