Wide versus narrow margins after partial hepatectomy for hepatocellular carcinoma: Balancing recurrence risk and liver function

doi:10.1016/j.amjsurg.2017.06.002

The American Journal of Surgery

Volume 214, Issue 2, August 2017, Pages 273-277

https://doi.org/10.1016/j.amjsurg.2017.06.002 Get rights and content

Abstract

Background

The goal of this study was to compare the outcome after partial hepatectomy for hepatocellular carcinoma (HCC) in which a margin less than or equal to 5 mm or greater than 5 mm was achieved.

Methods

A review of our 3300-patient prospective HPB database was performed from 12/2002 to 4/2015. Patients were stratified into two groups: resection margins ≤5 (“narrow”) and >5 mm (“wide”) as measured on final pathologic assessment.

Results

One-hundred thirty patients were included in the analysis (margin ≤5 mm, n = 41 and margin >5 mm, n = 89). At the time of analysis 54 patients had developed 56 recurrences, 15 (37%) in the narrow margin group and 41 (46%) in the wide margin group, p = 0.45. The pattern of recurrence was similar in the two groups: intrahepatic 11 (79%) versus 30 (75%), p = 1, and extra-hepatic 6 (43%) versus 17 (43%), p = 1. Median disease-free survival was similar in both groups, 18.1 versus 19.5 months (p = 0.85).

Conclusions

A narrow resection margin (5 mm or less) does not detract from oncologic outcomes after partial hepatectomy for HCC. Tailoring resection margins may lead to greater preservation of hepatic parenchyma. Factors other than margin status represent the driving forces for local and systemic recurrence.

Introduction

Multiple factors that relate to the recurrence of hepatocellular carcinoma (HCC) after resection are being studied.1, 2, 3 These factors include, among others, resection margin width. While studies show a positive margin status adversely affects long-term recurrence, the specifics regarding surgical margin size are debated.4, 5 Quantitatively, studies have shown a spectrum of values decreased postoperative recurrence.2, 6, 7 The obvious concern for a narrow-margin resection is recurrence, while a wide-margin resection could affect overall survival.5, 8 The precise balance of these two factors has not been evaluated.

The effect of surgical margin resection on long-term survival and recurrence-free survival is still controversial because recurrence after primary resection is multifactorial. Some predictors of recurrence include the need for a blood transfusion,⁹ underlying liver disease, and tumor characteristics. A prospectively collected database was utilized to examine some of these predictors of recurrence in relation to resection margin. The goal of our study was to examine the effects of surgical margin ≤5 mm versus margin >5 mm on postoperative recurrence and survival after primary resection of HCC.

Section snippets

Patient selection & categorization

Institutional review board approval was obtained from the University of Louisville. Signed consent forms were obtained prior to collection of any data. All study conduct followed appropriate good clinical and research practices. A single-center retrospective study was performed utilizing the University of Louisville Department of Surgical Oncology Hepato-pancreatico-biliary database. Patients diagnosed with HCC by pathology reports between December 2002 and April 2016 were considered for

Discussion

At present, surgical resection is considered one of the best options that can provide long-term cure to patients diagnosed with HCC.¹⁴ Surgical resection, however, has been known to cause recurrence.7, 14 The reason for recurrence development is not fully understood. Therefore, the goal of this study was to evaluate the outcomes for patients undergoing partial hepatectomy with margins of either “narrow” or “wide”. No major differences were seen across most of the metrics used to evaluate

Disclosure

The authors have nothing to disclose regarding conflict of interest that could interfere with the content of this article.

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Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma
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Citation Excerpt :
The RM width reported by pathologists was defined as the shortest distance from the tumor edge to the RM of the parenchyma. A cutoff value of 5 mm for the RM width was set to subdivide patients into two groups, including the narrow RM group (< 5 mm) and the wide RM group (≥ 5 mm), as suggested by previous reports [2,8,9,21]. Patients were followed up at the outpatient clinic after discharge according to the standard protocol of our center.
The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC.
Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed.
A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively).
As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.
Adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis
2020, Clinics and Research in Hepatology and Gastroenterology
Microvascular invasion (MVI) has been associated with a poor prognosis for hepatocellular carcinoma (HCC) patients. This study aimed to evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy for HCC with MVI.
An online search on Embase and Ovid MEDLINE(R) was conducted to identify the appropriate articles published prior to March 11, 2019. The primary endpoint was the overall survival (OS) of patients treated using adjuvant TACE after hepatectomy (HTAT) versus hepatectomy (HT) alone for HCC with MVI. The secondary endpoints were disease-free survival (DFS) and safety.
Seven studies with 1869 patients were included in this analysis. Meta-analyses demonstrated that HTAT was superior to HT in OS (Hazard Ratio [HR]: 0.67, 95%CI: 0.58–0.77, P < 0.001) and DFS (HR: 0.71, 95%CI: 0.62–0.81, P < 0.001) for treating HCC with MVI. Subgroup analysis revealed that for early-stage HCC, HTAT was associated with longer OS (P = 0.009) and DFS (P = 0.066) as compared with HT. For HCC larger than 5 cm, HTAT also prolonged the DFS (P = 0.008) of patients, but the difference in OS was not statistically significant (P = 0.266). Adjuvant TACE commonly caused nausea and vomiting, liver dysfunction, leucopenia, pain, and fever.
Adjuvant TACE after hepatectomy is effective and safe for patients with HCC accompanied by MVI. However, the benefit of adjuvant TACE in patients who have HCC with a diameter >5 cm is not clear. Further randomized controlled studies are warranted to test these conclusions.
Impact of narrow margin and R1 resection for hepatocellular carcinoma on the salvage liver transplantation strategy. An intention-to-treat analysis
2019, HPB
Citation Excerpt :
R1 resection has been shown to be associated with a higher recurrence risk17 and to be a poor prognostic factor for survival.17 Various definitions of R1 resection have been proposed including microscopic exposure of the tumor and vascular surface,24 microscopic involvement of the line of transection by the main tumor,9,17,18,20 or venous tumor or satellite nodules.17 According to the results of our study, R1 resection cannot be considered as a contraindication to further transplantation, and more importantly, R1 resection might not be an indication i) to enlarge the resection upon intraoperative diagnosis of narrow or R1 margins, ii) for adjuvant treatment or iii) to shift from a salvage to a bridge transplantation strategy.
No studies have investigated whether narrow margin is a risk factor for hepatocellular carcinoma recurrence outside transplantability criteria. The objective was to assess on an intent-to-treat (ITT) basis whether hepatectomy with narrow margin affects the outcomes in patients enrolled in the salvage liver transplantation (LT) strategy.
From 2007 to 2016, patients enrolled in the salvage LT strategy were divided into 2 groups: narrow (<10 mm) vs. wide (≥10 mm) margin groups. R1 resection was defined as positive histologic margin involvement. Recurrence rate, transplantability rate of recurrence and ITT overall survival (ITT-OS) were evaluated.
A total of 81 patients were studied: 43 patients with narrow margin and 38 with wide margin. The recurrence rates, pattern and delay of recurrence, transplantability following recurrence, and ITT-OS were similar between the two groups. These results were maintained when comparing patients with R1 resection to those with R0 resection.
On an ITT basis, hepatectomy with narrow margin or R1 resection did not impair the transplantability of recurrence and survival of patients enrolled in the salvage LT strategy. Narrow margin and even R1 resection following hepatectomy in the setting of salvage LT strategy should not be the basis for altering the strategy.
Is R1 vascular hepatectomy for hepatocellular carcinoma oncologically adequate? Analysis of 327 consecutive patients
2019, Surgery (United States)
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The adequate surgical margin for HCC has been investigated in many studies. Some reported that narrow and positive margins were associated with worse survival, and other studies demonstrated conflicting results.5–14 These contradictory findings have resulted in a variable set of resectability criteria among surgical centers.
R1 vascular resection for liver tumors was introduced in the early twenty-first century. However, its oncologic adequacy remains controversial. The aim of this study was to determine the oncologic adequacy of R1 vascular hepatectomy in hepatocellular carcinoma patients.
A prospective cohort of patients with hepatocellular carcinoma resected between the years 2005 and 2015 was reviewed. R0 was any resection with a minimum 1 mm of negative margin. R1 vascular was any resection with tumor exposure attributable to the detachment from major intrahepatic vessel. R1 parenchymal was any resection with tumor exposure at parenchymal margin. The end points were the calculation of the local recurrence of R0, R1 parenchymal, and R1 vascular hepatectomy and their prognostic significances.
We analyzed 327 consecutive patients with 532 hepatocellular carcinoma and 448 resection areas. We found that 205 (63%) resulted R0, 56 (17%) resulted R1 parenchymal, 50 (15%) resulted R1 vascular, and 16 (5%) resulted both R1 parenchymal and R1 vascular. After a median follow-up of 33.5 months (range 6.1–107.6), the 5-year overall survival rates were 54%, 30%, 65%, and 36%, respectively for R0, R1 parenchymal, R1 vascular, and R1 parenchymal + R1 vascular (P = .031). Local recurrence rates were 3%, 14%, 4%, and 19%, respectively for R0, R1 parenchymal, R1 vascular, and R1 parenchymal + R1 vascular (P = .001) per patient, and 4%, 4%, 12%, and 18%, respectively for R0, R1 vascular, R1 parenchymal, and R1 parenchymal + R1 vascular (P = .001) per resection area. At multivariate analysis R1 parenchymal and R1 vascular + R1 parenchymal were independent detrimental factors.
R1 vascular hepatectomy for hepatocellular carcinoma is not associated with increased local recurrence or decreased survival. Thus, detachment of hepatocellular carcinoma from intrahepatic vessels should be considered oncologically adequate.
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Impact of Surgical Margin Width on Prognosis Following Resection of Hepatocellular Carcinoma Varies on the Basis of Preoperative Alpha-Feto Protein and Tumor Burden Score
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Wide versus narrow margins after partial hepatectomy for hepatocellular carcinoma: Balancing recurrence risk and liver function

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patient selection & categorization

Discussion

Disclosure

J Gastrointest Surg Off J Soc Surg Aliment Tract

J Am Coll Surg

Am J Surg

Am J Surg

Eur J Cancer

HPB Off J Int Hepato Pancreato Biliary Assoc

Formos J Surg

J Am Coll Surg

Lesson from 610 liver resections of hepatocellular carcinoma in a single center over 10 years

World J Surg Oncol

Significance of resection margin in hepatectomy for hepatocellular carcinoma: a critical reappraisal

Ann Surg