The Role of Liver-Directed Surgery in Patients With Hepatic Metastasis From Primary Breast Cancer: a Multi-Institutional Analysis

BACKGROUND: Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM). METHODS: Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed. RESULTS: Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS. DISCUSSION: In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection.info:eu-repo/semantics/publishedVersio

Intraoperative Surgical Margin Re-resection for Colorectal Liver Metastasis: Is It Worth the Effort?

This study was conducted to evaluate recurrence and survival among patients who underwent intraoperative margin re-resection for colorectal cancer liver metastases (CRLM). Among patients who receive intraoperative margin re-resection, the relation between final margin status, pattern of recurrence, and survival is largely unknown. Three hundred thirty-two patients who underwent hepatic resection for CRLM between 2000 and 2013 were identified. Demographics, operative data, pathologic margin status, site of recurrence, and long-term survival data were collected and analyzed. Patients were stratified in three groups based on their margin status: R0, R1, and R1 -> aEuro parts per thousand R0. R0 resections were achieved in 247 (74.4 %) patients, 61 (18.4 %) patients had an R1 resection, whereas 24 (7.2 %) had an R1 -> aEuro parts per thousand R0. Median survival for patients undergoing R0 resections was 50.2 (95 % confidence interval (CI) 49.2-66.2) months versus 63.0 (95 % CI 50.3-70.5) months for patients undergoing R1 resections versus 49.2 (95 % CI 29.9-NA) months for patients undergoing intraoperative margin re-resection (P > 0.05). Differences in recurrence rate and pattern were not significant between the three groups (P > 0.05). In the era of modern systemic chemotherapy, it seems that the impact of margin status on outcomes may be minimal compared to that of patient and tumor factors. In this scenario, margin re-resection to achieve R0 status does not improve long-term outcomes

Effect of KRAS mutation on long-term outcomes of patients undergoing hepatic resection for colorectal liver metastases

282 Background: The impact of KRAS mutation on overall (OS) and recurrence-free (RFS) survival of patients with colorectal liver metastases (CLM) remains poorly defined. We sought to investigate the prognostic value of KRAS in a large cohort of patients undergoing liver resection for CLM. Methods: Between 2003 and 2013, 334 patients underwent hepatic resection for CLM at Johns Hopkins Hospital and met the inclusion criteria. Somatic mutations at codons 12/13 were evaluated through a sequencing analysis of the tumor samples. Clinicopathological characteristics, perioperative details, and outcomes were stratified by KRAS status (mtKRAS vs. wtKRAS) and analyzed. Results: Among 334 patients undergoing liver resection for CLM, mtKRAS was identified in 115 (34.4%) patients. Median CEA was 7.3 ng/dL; 40.4% of patients had a solitary tumor and median tumor size was 2.5 cm. At a median follow-up of 28.2 months, recurrence was observed in 59 (51.3%) patients with mtKRAS and 117 (53.4%) patients with wtKRAS (P=0.71); there was no difference in the pattern of recurrence (liver: mtKRAS, 39.0% vs. wtKRAS, 52.1%; lung: mtKRAS, 55.6% vs. wtKRAS, 64.3%; both P>0.05). While 5-year log-rank OS was comparable among mtKRAS (41.6%) vs. wtKRAS (48.5%), on multivariable Cox survival analysis mtKRAS was associated with worse OS(HR, 1.65; 95%CI, 1.07-2.54). Moreover, among patients who experienced a recurrence, 5-year OS was worse among those patients who had mtKRAS (mtKRAS, 28.1% vs. wtKRAS, 44.5%; P=0.004). After controlling for tumor factors, as well as receipt of chemotherapy, mtKRAS status remained independently associated with a worse outcome among patients who recurred(HR 2.07, 95% CI 1.31-3.27; P=0.002). Conclusions: mtKRAS was noted in one-third of patients with CLM. While KRAS status did not impact pattern of recurrence, mtKRAS was an independent predictor of worse OS among patients who experienced a recurrence following resection of CLM. mtKRAS was identified in 115 (34.4 %) patients. At a median follow-up of 28.2 months, recurrence was observed in 59 (51.3 %) patients with mtKRAS and 117 (53.4 %) patients with wtKRAS (P = 0.79); there was no difference in the pattern of recurrence (liver: mtKRAS 39.0 % vs. wtKRAS 52.1 %; lung: mtKRAS 55.6 % vs. wtKRAS 64.3 %; both P > 0.05). Although 5-year log-rank overall survival (OS) was comparable among mtKRAS (41.6 %) vs. wtKRAS (48.5 %), on multivariable Cox survival analysis and after adjusting for known predictors of OS mtKRAS was associated with worse OS (hazard ratio 1.65; 95 % confidence interval 1.07-2.54; P = 0.02). Among patients who experienced a recurrence, 5-year OS was worse among those patients who had mtKRAS (mtKRAS 28.1 % vs. wtKRAS 44.5 %; P = 0.004). After controlling for tumor factors and receipt of chemotherapy, mtKRAS status remained independently associated with a worse outcome among patients who experienced recurrence (hazard ratio 2.07; 95 % confidence interval 1.31-3.27; P = 0.002). mtKRAS was noted in one-third of patients with CRLM. Although KRAS status did not affect the pattern of recurrence and recurrence-free survival, mtKRAS was an independent predictor of worse OS. The effect was more pronounced among patients who experienced a recurrence after resection of CRLM

Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio in Patients After Resection for Hepato-Pancreatico-Biliary Malignancies

Background and ObjectivesWe sought to determine whether Neutrophil-lymphocyte ratio (NLR) or platelet-lymphocyte ratio (PLR) were associated with outcomes of patients undergoing surgery for a hepatopancreatico-biliary (HPB) malignancy. MethodBetween 2000 and 2013, 452 patients who underwent an HPB procedure for a malignant indication were identified. Clinicopathological characteristics, NLR, and PLR, as well as short- and long-term outcomes were analyzed. High NLR and PLR were classified using a cut-off value of 5 and 190, respectively, based on ROC curve analysis. ResultsPatients with low versus high NLR and PLR had similar baseline characteristics with regard to performance status and tumor stage (all P>0.05). Elevated PLR (HR=1.40) tends to be association with shorter recurrence-free survival (RFS) (P=0.05), whereas NLR was not a predictor of shorter RFS. Differently, both elevated NLR (HR=1.94) and PLR (HR=1.79) were associated with worse overall survival (OS) (both P<0.05). Patients with NLR 5 and those with PLR 190 had a significantly shorter OS compared to patients with NLR <5 and PLR <190, respectively (log-rank test, both P<0.05). Moreover, patients who had both NLR and PLR elevated had worse OS compared to patients with either one or none inflammatory markers elevated (log-rank P=0.02). ConclusionElevated NLR and PLR were predictors of worse long-term outcome among patients with HPB malignancy undergoing resection. J. Surg. Oncol. 2015 111:868-874. (c) 2014 Wiley Periodicals, Inc

Lymph Node Status After Resection for Gallbladder Adenocarcinoma: Prognostic Implications of Different Nodal Staging/Scoring Systems

Background and ObjectivesSeveral lymph node (LN) staging/scoring systems have been proposed to stratify the prognosis of patients with gallbladder adenocarcinoma (GBA). We sought to define the prognostic performance of the most commonly utilized LN staging/scoring systems including AJCC/UICC N stage, lymph node ratio (LNR), log odds (LODDS), and N score, among patients with GBA. MethodBetween 2004 and 2010, 1,124 patients with GBA were identified from the Surveillance Epidemiology and End Results (SEER) database. The discriminative ability of each LN staging/scoring system was assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index. ResultsWhen assessed using categorical values, LNR had a modest, improved ability to discriminate patients with regard to prognosis (C-index: 0.615; AIC: 2118.2) compared with AJCC/UICC N stage or N score and a prognostic discrimination comparable to LODDS. Among patients who had a total number of LN examined (TNLE) of 1 or 2, all the staging/scoring systems performed comparably. In contrast, among patients who had 4 TNLE, LODDS performed the best (C-index: 0.613; AIC: 303.2). ConclusionThe performance of the different LN staging/scoring systems varied based on the TNLE. In particular, for patients who had 4 TNLE, LODDS out-performed the other staging/scoring systems. J. Surg. Oncol. 2015 111:299-305. (c) 2014 Wiley Periodicals, Inc

Benign Solid Tumors of the Liver: Management in the Modern Era

Recently, there has been a growing interest in solid benign liver tumors as the understanding of the pathogenesis and molecular underpinning of these lesions continues to evolve. We herein provide an evidence-based review of benign solid liver tumors with particular emphasis on the diagnosis and management of such tumors. A search of all available literature on benign hepatic tumors through a search of the MEDLINE/PubMed electronic database was conducted. New diagnostic and management protocols for benign liver tumors have emerged, as well as new insights into the molecular pathogenesis. In turn, these data have spawned a number of new studies seeking to correlate molecular, clinicopathological, and clinical outcomes for benign liver tumors. In addition, significant advances in surgical techniques and perioperative care have reduced the morbidity and mortality of liver surgery. Despite current data that supports conservative management for many patients with benign liver tumors, patients with severe preoperative symptomatic disease seem to benefit substantially from surgical treatment based on quality of life data. Future studies should seek to further advance our understanding of the underlying pathogenesis and natural history of benign liver tumors in order to provide clinicians with evidence-based guidelines to optimize treatment of patients with these lesions

Surgical Management of Intrahepatic Cholangiocarcinoma: Defining an Optimal Prognostic Lymph Node Stratification Schema

Metastatic disease to the regional lymph node (LN) is a strong predictor of worse long-term outcome after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). The objectives of this study were to assess the prognostic performance of American Joint Committee on Cancer (AJCC)/International Union Against Cancer, 7th edition, N stage, LN ratio (LNR), and log odds of metastatic LN (LODDS) staging criteria in patients with ICC. The surveillance, epidemiology, and end results cancer registry was queried to identify 749 patients who underwent surgical resection of ICC during 1988-2011. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze survival. The relative discriminative abilities of the different LN staging systems were assessed by the Harrell concordance index (c statistic). Of the 749 patients, 477 (63.7 %) had no LN metastasis, while 272 (36.3 %) had LN metastasis. Patients with LN metastasis had an increased risk of death (hazard ratio 2.42, 95 % confidence interval 1.98-2.95; P < 0.001). When assessed using categorical values, LNR (C index 0.620) and LODDS (C index = 0.630) showed a better prognostic performance than the AJCC 7th edition staging system (C index = 0.607). When assessed using continuous values, the LODDS staging system (C index = 0.626) slightly outperformed LNR (C index = 0.621). There was heterogeneity of outcomes among patients with no LN involved (LNR = 0) or all LN involved (LNR = 1), indicating that LODDS may better characterize and stratify outcomes among these groups. LODDS and LNR showed better prognostic performance than the AJCC 7th edition staging system. When assessed as categorical and continuous variables, LODDS outperformed LNR, especially among those patients with either very low or high LNR