Extended Right Hepatectomy for Hepatocellular Carcinoma

Annals of Surgical Oncology -     

活体肝移植供体及有或无肝硬变肝病患者右半肝切除术后预后的比较分析

目的探讨活体肝移植供体和肝病患者行右半肝切除术后的预后是否相似。方法纳入笔者所在医院肝脏移植中心2009～2010年期间的连续病例,包括40例不含肝中静脉的活体右半肝供体（活体肝移植供体组,简称LDLT-D组）及80例因肝病行右半肝切除的患者,其中40例为无肝硬变的肝病患者（无肝硬变肝病组,简称LD-NC组）及40例伴肝硬变的肝病患者（肝硬变肝病组,简称LD-WC组）。分析3组患者术前肝功能和一般临床资料,术中失血量和输血量,以及术后肝功能情况和并发症发生情况。结果 3组患者术前特征相似。LDLT-D组患者术中出血量较LD-NC组多〔（765±411）mL比（584±242）mL,P=0.008〕,与LD-WC组〔（666±224）mL〕接近（P=0.136）,但3组患者术中平均输血量相近（P=0.108）。术后第1天和第3天,LDLT-D组患者的TB和INR水平高于LD-NC组和LD-WC组（P〈0.05）,LD-WC组患者的ALT和AST水平均高于LDLT-D组和LD-NC组（P〈0.05）。LDLT-D组、LD-NC组及LD-WC组患者术后总并发症发生率分别是30.0%（12/40）、27.5%（11/40）和37.5%（15/40）,3组间的差异均无统计学意义（P=0.606）,但LD-WC组的ClavienⅢ级并发症发生率〔27.5%（11/40）〕高于LDLT-D组〔7.5%（3/40）〕及LD-NC组〔10.0%（4/40）〕,P=0.024。结论在右半肝切除术后早期阶段,活体肝移植供体肝功能损害更重;活体肝移植供体、无肝硬变的肝病患者和伴肝硬变的肝病患者术后总并发症发生率相近,但伴肝硬变肝病患者的严重并发症发生率高于活体肝移植供体及无肝硬变肝病患者。     

Prognosis and Predictors of Surgical Complications in Hepatocellular Carcinoma Patients With or Without Cirrhosis after Hepatectomy

Background

Although poor liver function is associated with a high morbidity rate and poor prognosis in hepatocellular carcinoma (HCC) patients, the exact effects of liver pathology on the surgical outcomes of HCC patients are poorly understood. The purpose of this study was to assess how the liver pathology of HCC patients affects their prognosis and complications rate after liver resection.

Methods

Between January 2006 and November 2010, 149 consecutive hepatocellular carcinoma patients, including 79 noncirrhosis patients and 70 cirrhosis patients, were enrolled in this study.

Results

Among the noncirrhotic patients, operative time, fresh frozen plasma (FFP) transfusion requirement, tumor size, and serum retinol binding protein (RBP) levels were significantly higher in the complications group than in the complications-free groups. On the other hand, in the cirrhotic patients the prothrombin time (PT) and indocyanine green retention value at 15 min (ICGR₁₅) of the complications group were significantly lower and higher, respectively, than those of the complications-free group. In the noncirrhotic patients, recurrence-free survival and overall survival did not differ between the complications and complications-free groups. On the other hand, in the cirrhotic patients, the recurrence-free survival and overall survival of the complications-free group were significantly longer than those of the complications group.

Conclusions

In the noncirrhotic patients, surgical complications had no prognostic effect, whereas they had a significant survival impact in the cirrhotic patients. The surgical strategy for HCC should be based on the patient’s pathological background.     

ICG Clearance in Assessing Cirrhotic Patients with Hepatocellular Carcinoma for Major Hepatic Resection

Objective: To deWne the safety of major hepatectomy for hepatocellular carcinoma (HCC) associated with cirrhosis and the selection criteria for surgery in terms of hospital mortality. Design: Major hepatectomy for HCC in the presence of cirrhosis is considered to be contraindicated by many surgeons because the reported mortality rate is high (26% to 50%). Previous workers recommended that only selected patients with Child''s A status or indocyanine green (ICG) retention at 15 minutes of less than 10% undergo major hepatectomy. A survery was made, therefore, of our patients with HCC and cirrhosis undergoing major hepatectomy between 1989 and 1994. Setting: A tertiary referral center. Patients: The preoperative, intraoperative, and post-operative data of 54 patients with cirrhosis who had major hepatectomy were compared with those of 25 patients with underlying chronic active hepatitis and 22 patients with normal livers undergoing major hepatectomy for HCC. The data had been prospectively collected. Intervention: Major hepatectomy, defined as resection of two or more liver segments by Goldsmith and Woodburn nomenclature, was performed on all the patients. Main Outcome Measure: Hospital mortality, which was defined as death within the same hospital admission for the hepatectomy. Results: Preoperative liver function in patients with cirrhosis was worse than in those with normal livers. The intraoperative blood loss was also higher (P=.01), but for patients with cirrhosis, chronic active hepatitis, and normal livers, the hospital mortality rates (13%, 16%, and 14%, respectively) were similar. The hospital mortality rate for patients with cirrhosis in the last 2 years of the study was only 5%. Patients with cirrhosis could tolerate up to 10 L of blood loss and survive the major hepatectomy. By discriminant analysis, an ICG retention of 14% at 15 minutes was cutoff level that could maximally separate the patients with cirrhosis with and without mortality. Conclusion: Major hepatectomy for HCC in the presence of cirrhosis is associated with a mortality rate that is not different from the rate for patients with normal livers. An ICG retention of 14% at 15 minutes would serve as a better selection criterion than the 10% previously used.     

Hepatectomy for Hepatocellular Carcinoma in Elderly Patients Aged 75 Years or More

Background  The aim of this study was to clarify the characteristics of elderly hepatocellular carcinoma (HCC) patients aged 75 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Methods  Between January 1990 and December 2006, 570 patients underwent curative hepatectomy for HCC. Elderly patients were defined as those aged 75 years or more. Clinicopathological data and outcomes after hepatectomy for 64 elderly and 502 younger patients were prospectively collected and compared. Results  The proportion of elderly patients with chronic viral infection was less than that of younger patients (p < 0.001). Cirrhotic patients in the elderly group were less than those in the younger group (p = 0.03). The elderly patients had better liver function than did the younger patients (p = 0.007) but had more advanced HCC with microscopic vascular invasion than did the younger patients (p = 0.04). There was no operative mortality in the elderly patients and there was no significant difference in postoperative complication rates and long-term survival after hepatectomy between the two groups. Conclusions  Hepatectomy for elderly patients with resectable HCC is safe and feasible. Selected elderly patients with HCC might benefit from hepatectomy. This work originated from the Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.     

Significant Long-Term Survival After Radiofrequency Ablation of Unresectable Hepatocellular Carcinoma in Patients with Cirrhosis

Background Radiofrequency ablation (RFA) offers an alternative treatment in some unresectable hepatocellular carcinoma (HCC) patients with disease confined to the liver. We prospectively evaluated survival rates in patients with early-stage, unresectable HCC treated with RFA.Methods All patients with HCC treated with RFA between September 1, 1997, and July 31, 2002, were prospectively evaluated. Patients were treated with RFA by using a percutaneous or open intraoperative approach with ultrasound guidance and were evaluated at regular intervals to determine disease recurrence and survival.Results A total of 194 patients (153 men [79%] and 41 women [21%]) with a median age of 66 years (range, 39–86 years) underwent RFA of 289 sonographically detectable HCC tumors. All patients were followed up for at least 12 months (median follow-up, 34.8 months). Percutaneous and open intraoperative RFA was performed in 140 (72%) and 54 (28%) patients, respectively. The median diameter of tumors treated with RFA was 3.3 cm. Disease recurred in 103 (53%) of 194 patients, including 69 (49%) of 140 patients treated percutaneously and 34 (63%) of 54 treated with open RFA (not significant). Local recurrence developed in nine patients (4.6%). Most recurrence was intrahepatic. The overall complication rate was 12%. Overall survival rates at 1, 3, and 5 years for all 194 patients were 84.5%, 68.1%, and 55.4%, respectively.Conclusions Treatment with RFA can produce significant long-term survival rates for cirrhotic patients with early-stage, unresectable HCC. RFA can be performed in these patients with relatively low complication rates. Confirmation of these results in randomized trials should be considered.Presented at the 57th Annual Cancer Symposium of the Society of Surgical Oncology, New York, New York, March 18–21, 2004.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Outcome Comparison of Right Hepatectomy for Living Liver Donation Versus for Hepatic Patients Without Cirrhosis

Background  

Hepatectomy is one of the primary methods used in the treatment of hepatic lesions and liver graft harvesting. However, few studies have evaluated the postoperative recovery process of donor patients and that of normal liver hepatic patients following a right hepatectomy procedure.     

Hepatic Resection for Hepatocellular Carcinoma Meeting Milan Criteria in Child-Turcotte-Pugh Class A Patients With Cirrhosis

This study evaluated whether hepatic resection is a reasonable strategy as an initial treatment for hepatocellular carcinoma (HCC) meeting Milan criteria in patients with compensated cirrhosis. From the database of 435 consecutive patients with resection of HCC between July 1994 and May 2007, 213 patients were found to have Child-Turcotte-Pugh class A cirrhosis and HCC meeting Milan criteria, as shown by preoperative image studies. We examined long-term survivals and patterns of recurrence after hepatic resection among those patients. Overall survival rates at 1, 3, 5, and 10 years were 92%, 78%, 69%, and 52%, respectively, and 1-, 3-, 5-, and 10-year disease-free survival rates were 79%, 57%, 44%, and 19%, respectively. Pathological review indicated that 36/213 patients (16.9%) had another nodule and/or gross vascular invasion. Microvascular invasion, tumor size, and histological grade of cirrhosis were independent risk factors for recurrence. Sixty percent of recurrent cases met the Milan criteria. The six patients who underwent living donor salvage liver transplantation (OLT) for intrahepatic recurrence were alive without recurrence at a median of 24 (range = 8-31) months. These favorable data suggest that hepatic resection is a good option for small HCCs in patients with compensated cirrhosis; and salvage OLT may be reserved for patients with recurrences.     

肝癌切除联合脾切除治疗肝细胞癌合并脾功能亢进的体会

目的探讨肝细胞癌合并脾功能亢进患者同期行肝癌切除和脾切除的安全性及可行性。方法回顾性分析2001年11月至2012年4月期间笔者所在医院收治的52例肝细胞癌合并脾功能亢进同期施行肝癌切除和脾切除患者的临床资料。结果肝癌切除联合脾切除19例,肝癌切除联合脾切除加贲门周围血管离断术33例。手术时间（249．63±40．90）min（182～340min）,术中出血量（580．77±260．31）mL（200～1700）mL。全组无死亡病例,术后并发症包括：胸腔积液11例,肺内感染3例,肝断面感染3例,胆汁漏1例,切口感染2例,高胆红素血症3例,门静脉系统血栓形成22例,均经保守治疗后好转。术后第14天,患者的白细胞和血小板计数分别由术前的（3．19±1．59）×10^9／L和（53．96±18．94）×109／L升至（8．86±5．06）×10^9／L和（464．90±189．27）×10^9／L（｜P〈0．05）;术后红细胞计数变化不明显,甚至有轻度下降。结论对于肝细胞癌合并脾功能亢进患者,选择合适的病例同期行肝癌切除和脾切除是安全可行的,而且脾切除有助于缓解脾功能亢进。     

Short- and Long-Term Outcomes after Hepatic Resection for Hepatocellular Carcinoma with Concomitant Esophageal Varices in Patients with Cirrhosis

Background Hepatic resection for hepatocellular carcinoma (HCC) in cirrhotic patients with esophageal varices (EV) is often avoided because of poor liver function reserve. Outcomes of resection in such cases have not been fully investigated. Methods We conducted a retrospective study of 134 cirrhotic patients (Child–Pugh class A or B) who underwent hepatic resection for HCC, comparing short- and long-term outcomes in patients with EV (n = 31) to those in patients without EV (n = 103). Results Patients with EV had higher tumor differentiation, fewer instances of portal invasion, lower liver function reserve, and more limited resections than did patients without EV. Of 31 patients with EV, four died of postoperative complication, and nine of liver failure, seven of HCC, two of ruptured EV, and two of other causes. Median survival time for patients who died of liver failure was 59 months. Mortality and morbidity rates after hepatic resection did not differ between patients with and without EV. The 5-year overall survival rate was significantly higher in patients with EV (70.1%) than in those without EV (47.5%, P = 0.045) but did not differ between patients without portal invasion with and without EV (P = 0.55). Presence of EV was not an independent predictor for survival. Conclusions Short- and long-term outcomes of hepatic resection in HCC patients with and without EV are similar. Limited hepatic resection for early-stage tumor is an option for Child–Pugh class A or B patients with EV.     

影响中晚期肝细胞肝癌手术切除预后的多因素分析

目的：探讨影响中晚期肝细胞肝癌手术切除预后的因素。方法：对130例中晚期大肝癌随访1-7年，采用单因素、多因素分析统计不同预后因素对患生存率的影响。结果：手术后1，3，5年生存率分别为81．7％，24．3％，18．4％。单因素分析提示影响预后的因素为肝癌大小、是否早期复发、肝硬化情况、输血量；多因素分析提示肝癌大小、肿瘤早期复发是影响肝癌术后的预后因素。结论：中晚期肝癌手术切除预后仍不理想，重视围手术期处理，预防术后早期复发有望提高手术疗效。     

Clinicopathologic Features of Hepatocellular Carcinoma Patients with Compensated Cirrhosis Surviving More than 10 Years after Curative Hepatectomy

BACKGROUND: The aim of this study was to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients with compensated cirrhosis surviving more than 10 years after initial hepatectomy. STUDY DESIGN: Among 250 patients who underwent hepatectomy for HCC between 1987 and 1994 at our institute, 145 patients who had Child-Pugh class A liver function and who underwent curative resection were included in this study. Clinicopathologic factors in 10-year survivors and patients who died within 10 years (nonsurvivors) were compared, and the prognostic factors affecting survival were identified. RESULTS: There were 29 patients who survived for more than 10 years after initial hepatectomy, and 9 of those patients survived without cancer recurrence. The 3-, 5-, and 10-year survival rates were 76.2%, 53.0%, and 26.9% respectively. The corresponding disease-free survival rates were 43.1%, 25.7%, and 9.9% respectively. In multivariate analysis, liver fibrosis grade F0-2, female gender, ICG-R15 value of less than 15%, and absence of microscopic vascular invasion were favorable independent factors associated with 10-year survival. Disease-free interval after initial hepatectomy in 10-year survivors with recurrence was significantly longer than that in nonsurvivors with recurrence, 5.1 and 1.9 years respectively (P = 0.0004). The number of intrahepatic recurrent nodules in 10-year survivors tended to be fewer than that in nonsurvivors. CONCLUSIONS: Based on the results of our study, liver fibrosis grade F0-2, female gender, ICG-R15 value of less than 15% and absence of microscopic vascular invasion at initial hepatectomy might be biologically favorable conditions for long-term survival. Close follow-up as well as multimodal treatment could contribute to prolongation of survival in such patients, even if HCC recurrence develops.     

Prognosis of Hepatocellular Carcinoma after Hepatectomy in Patients with Renal Dysfunction

We evaluated the effect of renal dysfunction on the prognosis of hepatocellular carcinoma in 224 patients who underwent hepatic resection. Survival was compared between patients with (57 patients) and without renal dysfunction (116 patients), using a creatinine clearance 70 ml/min as the cut-off value. There were no significant differences with respect to other preoperative characteristics, operative findings, or histology between the two groups. There was also no difference in survival between the two groups after hepatic resection. However, among 132 patients with a solitary tumor measuring 5 cm in greatest dimension, the disease-free and overall survival rates of 36 patients with renal dysfunction were significantly worse after resection than those of the patients without renal dysfunction (p = 0.04 and p = 0.0003, respectively). By multivariate analysis, renal dysfunction was an independent factor indicating a poor prognosis for disease-free and overall survival after resection of small solitary tumors (p = 0.0401 and p = 0.0031, respectively). Renal dysfunction did not affect the overall prognosis after resection of hepatocellular carcinoma, but it worsened the prognosis of patients with small solitary lesions.     

Hepatic Resection is Justified for Elderly Patients with Hepatocellular Carcinoma

BACKGROUND: Hepatic resection is one of the main treatment modalities for patients with hepatocellular carcinoma (HCC); however, surgery is generally stressful and often is avoided for elderly patients. This retrospective study was designed to determine whether the indications for hepatic resection in younger patients with HCC are applicable to elderly patients. METHODS: Subjects were 294 patients in whom 319 hepatic resections were performed for HCC (male/female ratio, 238/81; age range, 18-83 years). The patients were divided into two groups according to age at the time of surgery: 70 years or older (n = 109) and 69 years or younger (n = 210). Surgical strategy and postoperative follow-up methods did not differ between groups. The incidence and severity of postoperative complications classified by the Clavien system were compared between the two groups. Postoperative survival was compared between the two groups and between subgroups based on Japan Integrated Staging (JIS) scores. HCC-related death rates also were compared. RESULTS: No significant between-group difference was found in background liver function or type of hepatic resection. Differences were found in performance status and type of hepatitis virus infection. No difference was observed in the incidence or severity of postoperative complications. Postoperative survival was similar between the two age-based study groups and between the JIS-based subgroups. HCC-related death rates did not differ between groups. CONCLUSIONS: The absence of differences in postoperative outcomes between groups suggests that hepatic resection is justified for HCC in selected patients aged 70 years or older.     

Hepatectomy as Treatment of Choice for Hepatocellular Carcinoma in Elderly Cirrhotic Patients

In recent decades liver resection has become a safe procedure; however, the outcome of hepatectomies in aged cirrhotic patients is often uncertain. To elucidate early and long-term outcomes of hepatectomy for HCC in the elderly, we studied 241 cirrhotic patients who underwent liver resection for HCC between 1985 and 2003. According to their age at the time of surgery, patients were divided into two groups: aged > 70 years (64 patients) and aged ≤ 70 years (177 patients). Operative mortality was 3.1% in the elderly and 9.6% in the younger group (p = 0.113). Postoperative morbidity and liver failure rates were higher in the younger group (42.4% versus 23.4%, p = 0.0073; 12.9% versus l.6%, p = 0.0065). Five-year survival rates are 48.6% in the elderly group and 32.3% in the younger group (p = 0.081). Considering only radical resections in Child-Pugh A patients, survival remains similar in the two groups (p = 0.072). Disease-free survival is not different in the two groups. A survival analysis performed according to the tumor diameter shows a better survival for elderly Child-Pugh A patients with HCC larger than 5 cm radically resected (50.8% versus 16.1% 5-year survival, p = 0.034). In univariate analysis, tumor size is not a prognostic factor in the elderly, whereas younger patients with large tumors have a worse outcome. Age by itself is not a contraindication for surgery, and selected cirrhotic patients with HCC who are 70 years of age or older could benefit from resection, even in the presence of large tumors. Long-term results of liver resections for HCC in the elderly may be even better than in younger patients.     

Selection Criteria for Hepatectomy in Patients with Hepatocellular Carcinoma Classified as Child-Pugh Class B

Background  

The appropriate surgical approach for hepatocellular carcinoma (HCC) patients of Child-Pugh class B is unclear. The aim of this study was to clarify the prognostic factors after hepatectomy in Child-Pugh class B patients and to delineate the selection criteria for hepatectomy.     

Outcome of Hepatectomy for Hepatocellular Carcinoma in Elderly Patients With Portal Hypertension

The outcome of liver resection (LR) for elderly hepatocellular carcinoma (HCC) patients with portal hypertension (PHT) who may be excluded as liver transplantation candidates has not been fully evaluated. One hundred ninety-five patients who underwent initial curative LR for HCC with PHT were divided into 2 groups: age <70 years (n = 131) and age ≥70 years (n = 64). Clinicopathologic data and postoperative complications were compared. Preoperative characteristics and postoperative complications were similar in both groups. However, in-hospital mortality was significantly more frequent in elderly than in younger patients (11% versus 1%, P = 0.002). No significant intergroup differences were observed in the 5-year disease-free survival rate or recurrence rate (19.7% versus 17.2%; P = 0.338, 63% versus 56%; P = 0.339). Although LR for elderly HCC patients with PHT can be performed with curative intent and gives results comparable with those in younger patients, it is associated with higher in-hospital mortality.Key words: Liver resection, Recurrence, Portal hypertension, Liver transplantation, Liver failureRecently, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing with the increased proportion of the geriatric population in Japan.^1,2 Thanks to recent advances in surgical techniques, perioperative management, and anesthesia, the indications for surgical treatment modalities such as liver resection (LR) or liver transplantation (LT) in elderly patients have expanded.^3,4 Thus, age itself is no longer a contraindication for liver surgery.When considering the treatment of HCC, most patients already have existing liver dysfunction due to chronic hepatitis or liver cirrhosis, and portal hypertension (PHT) may be present at the time of diagnosis.^5,6 The American Association for the Study of Liver Diseases (AASLD)/Barcelona Clinic for Liver Cancer (BCLC) Guidelines have been widely utilized for the management of HCC in Western countries.^7,8 They recommend that only LT can be regarded as curative treatment for early-stage HCC (single nodule or up to 3 nodules measuring ≤3 cm) with PHT. However, LT for all HCC patients with PHT is impossible because of donor organ shortage, especially in Asian counties.⁹ In addition, expanding the indications of LT for elderly patients is still controversial. A previous study suggested that patients with PHT who underwent LR showed the same incidence of postoperative complications and survival rate as patients without PHT.¹⁰ In other words, LR still plays an important role as the mainstay of curative treatment for HCC patients with PHT, even if they are elderly. There have been several reports on the safety and feasibility of LR for elderly HCC patients, but there is little information on the outcome of elderly patients with PHT, who are considered to be at extremely high risk.^11–16 Against this background, the aim of the present study was to examine the short- and long-term outcomes of LR in both elderly (age ≥70 years) and younger (age <70 years) HCC patients with PHT at a single center over a 12-year period.     

Extended Left Hepatectomy by Severing All Major Hepatic Veins with Reconstruction of the Right Hepatic Vein

Curative liver resection is technically challenging when multiple liver metastases from colon cancer involve the confluence of the three major hepatic veins. We report two cases of successful extended left hemihepatectomy achieved by severing all of the major hepatic veins together with the wall of the inferior vena cava, to resect liver metastases from colon cancer. Reconstruction of the right hepatic vein was done after unroofing the right anterior area of the liver with a direct anastomosis of the right hepatic vein. We did not need to perform total vascular exclusion or portovenous shunting during the liver transection. This simple and safe method can increase the surgical indications for previously unresectable tumors.