Takashi Mizuno

Hepatic atrophy following preoperative chemotherapy predicts hepatic insufficiency after resection of colorectal liver metastases

BACKGROUND & AIMS For patients with colorectal liver metastases (CLM) undergoing major hepatectomy, extensive preoperative chemotherapy has been associated with increased morbidity and mortality. The impact of extensive chemotherapy on total liver volume (TLV) change is unclear. The aims of the current study were twofold: (1) to determine the change of TLV following preoperative chemotherapy in patients undergoing resection for CLM and (2) to investigate the correlations among TLV change, postoperative hepatic insufficiency (PHI), and death from liver failure. METHODS Clinicopathological features of patients with CLM who underwent preoperative chemotherapy and curative resection were reviewed (2008-2015). TLV change (degree of atrophy) was defined as the percentage difference of TLV (estimated by manual volumetry)/standardized liver volume (SLV) ratio: ([Pre-chemotherapy TLV]-[Post-chemotherapy TLV])×100÷SLV (%). Receiver operating characteristic (ROC) analysis was performed to decide the accurate cut-off value of degree of atrophy to predict PHI. The Cox proportional hazard model was performed to identify the predictors of severe degree of atrophy and PHI. RESULTS The study cohort consisted of 459 patients, of which 154 patients (34%) underwent extensive preoperative chemotherapy (≥7 cycles). ROC analysis identified the degree of atrophy ≥10% as an accurate cut-off to predict PHI, which was significantly correlated with ≥7 cycles of preoperative chemotherapy. Four factors independently predicted PHI: standardized future liver remnant ≤30% (odds ratio [OR] 4.03, p=0.019), high aspartate aminotransferase-to-platelet ratio index (OR 5.27, p=0.028), degree of atrophy ≥10% (OR 43.5, p<0.001), and major hepatic resection (OR 5.78, p=0.005). Degree of atrophy ≥10% was associated with increased mortality from liver failure (0% [0/374] vs. 15% [13/85], p<0.001). CONCLUSION Extensive preoperative chemotherapy induced significant atrophic change of TLV. Degree of atrophy ≥10% is an independent predictor of PHI and death in patients with CLM undergoing preoperative chemotherapy and resection. LAY SUMMARY Extensive preoperative chemotherapy for patients with colorectal liver metastases (CLM) could induce hepatic atrophy. A higher degree of atrophy is an independent predictor of postoperative hepatic insufficiency and death in patients with CLM undergoing preoperative chemotherapy and resection.

Portal Vein Embolization: Tailoring, Optimizing, and Quantifying an Invaluable Procedure in Hepatic Surgery

In this issue, Yamashita et al. present the experience of the University of Tokyo with portal vein embolization (PVE) in 338 patients from 1995 to 2013. The authors should be congratulated for presenting an extensive review of their indication, technique, and outcome of PVE. Over the past two decades, PVE has become an invaluable procedure in hepatic surgery. This editorial is an opportunity to revisit the indications for the procedure, the techniques to optimize the hypertrophy, and the methods to quantify its effects on regeneration. In the study, Yamashita et al. used as indication for PVE a cut-off future liver remnant (FLR) volume of \40% in patients with normal liver function based on an indocyanine green retention rate at 15 min (ICGR15) of \10%. This cautious approach was associated with an excellent outcome following resection, with an hepatic insufficiency rate of 2% and 90-day mortality of 0.8%. Anatomically, the left liver, on average, accounts for 33% of the total liver volume (TLV), and a 40% cut-off implies that the majority of patients undergoing right hepatectomy should receive PVE, which seems unnecessary. As such, the 40% cut-off value for PVE is higher than the 20–30% used in the West, and the study may include more PVEs than clinically indicated. In our own experience with 301 extended right hepatectomies in patients with normal liver function, we demonstrated that patients with 20–30% FLR had similar postoperative outcomes compared with patients with 30–40% FLR, and only the subset of patients with B20% FLR had increased hepatic insufficiency and perioperative mortality. At MD Anderson Cancer Center, we recommend PVE for FLR of B20% in normal liver, B30% in injured liver, and B40% in fibrosis/cirrhosis. Using appropriate indications for PVE, tailoring the procedure based on accurate volumetry and avoiding overutilization are important because PVE remains a procedure with a 7.8% risk of associated complications, as reported in the series of the University of Tokyo. Yamashita et al. report an excellent degree of hypertrophy (median 10%) and kinetic growth rate (3.9–4.5% per week). In contrast, they report a median regeneration rate of 25% following PVE, which was lower than the regeneration rate of 62% following PVE in a recent series of 103 patients undergoing resection of colorectal liver metastases with small liver remnants. The lower regeneration rate in the series from the University of Tokyo may be attributed to generous indications for PVE and the performance of PVE in patients with an already large FLR unlikely to undergo significant regeneration. The technique recently used at the University of Tokyo is alcohol injection, which has led to less recanalization of the portal vein. It would have been interesting for the authors to compare the hypertrophy rates between alcohol injection and Gelfoam plus coil particle previously used by the authors. An important aspect of the technique at the University of Tokyo is the minimal use of segment 4 embolization (6/ 319, 1.9%) in spite of a large number of extended right hepatectomies (116/256, 45.3%). A major issue of right PVE without segment 4 embolization prior to extended right hepatectomy is the undesirable segment 4 regeneration at the expense of lesser regeneration of the left lateral bisegment. To counter this undesirable effect, at Nagoya University and MD Anderson Cancer Center, right PVE with segment 4 embolization has been used with a significant increase in the hypertrophy of the left lateral bisegment, compared with right PVE without segment 4 embolization. Society of Surgical Oncology 2017

Remnant Liver Ischemia as a Prognostic Factor for Cancer-Specific Survival After Resection of Colorectal Liver Metastases

Importance Ischemia-reperfusion injury during hepatic resection has been shown to accelerate progression of liver cancer. However, the prognostic relevance of remnant liver ischemia (RLI) after resection of colorectal liver metastases (CLMs) is unknown to date. Objectives To assess the prognostic influence of RLI after resection of CLMs and to identify correlates of greater extent of RLI. Design, Setting, and Participants This study was a retrospective analysis at The University of Texas MD Anderson Cancer Center based on prospectively collected data. The study identified 202 patients who underwent curative resection of CLMs between January 1, 2008, and December 31, 2014, and had enhanced computed tomographic images obtained within 30 days after surgery. Main Outcomes and Measures Remnant liver ischemia was defined as reduced or absent contrast enhancement during the portal phase. Postoperative RLI was classified as grade 0 (none), 1 (marginal), 2 (partial), 3 (segmental), or 4 (necrotic) as previously defined. Experienced members of the surgical team retrospectively performed imaging assessments. Team members were masked to the postoperative outcomes. Survival after resection was stratified by RLI grade. Predictors of RLI grade 2 or higher and survival were identified. Results Among 202 patients (median [range] age, 56 [27-87] years; 84 female), the RLI grades were as follows: grade 0 (105 patients), grade 1 (47 patients), grade 2 (45 patients), grade 3 (5 patients), and grade 4 (0 patients). Recurrence-free survival (RFS) and cancer-specific survival (CSS) rates after hepatic resection were worse in patients with RLI grade 2 or higher vs grade 1 or lower (RFS at 3 years, 6.4% [3 of 50] vs 39.2% [60 of 152]; P < .001 and CSS at 5 years, 20.7% [10 of 50] vs 63.7% [97 of 152]; P < .001). A largest metastasis at least 3 cm (OR, 2.74; 95% CI, 1.35-5.70; P = .005), multiple CLMs (OR, 2.51; 95% CI, 1.25-5.24; P = .009), and nonanatomic resection (odds ratio [OR], 3.29; 95% CI, 1.52-7.63; P = .002) were associated with RLI grade 2 or higher. A largest metastasis at least 3 cm (hazard ratio [HR], 1.70; 95% CI, 1.01-2.88; P = .045), mutant RAS (HR, 2.15; 95% CI, 1.27-3.64; P = .005), and RLI grade 2 or higher (HR, 2.90; 95% CI, 1.69-4.84; P < .001) were associated with worse CSS. Conclusions and Relevance In this study, remnant liver ischemia grade 2 or higher was associated with worse CSS after resection of CLMs. High-quality anatomic surgery to minimize RLI after resection is essential.

Loss of muscle mass during preoperative chemotherapy as a prognosticator for poor survival in patients with colorectal liver metastases

Background: The survival impact of specific body composition changes during preoperative chemotherapy in patients with colorectal liver metastases undergoing curative‐intent surgery remains unclear. This study aimed to determine the impact of changes in body weight and muscle mass during preoperative chemotherapy on survival after hepatectomy in patients with colorectal liver metastases. Methods: Consecutive patients with colorectal liver metastases undergoing preoperative chemotherapy and curative hepatectomy during 2009–2013 were retrospectively analyzed. Recurrence‐free and overall survival were examined according to body compositions, including muscle mass, as measured by skeletal muscle index (area of muscle [cm2]/square of height [m2]), and body weight before and after preoperative chemotherapy. Results: The median follow‐up duration in overall 169 patients was 47 months. Skeletal muscle index and body weight changed significantly during chemotherapy (skeletal muscle index: –0.52 cm2/m2, P = .03; body weight: +1.1 kg, P = .002). Patients with major muscle mass loss (≥7%) had significantly shorter median RFS than patients with no or minor muscle mass loss (<7%) (9.6 months vs 15.9 months; P = .02). Although major muscle mass loss was associated with poor outcome, skeletal muscle index before or after preoperative chemotherapy was not associated with recurrence‐free or overall survival. On multivariate analysis, major muscle mass loss was independently associated with poorer recurrence‐free survival (hazard ratio, 1.76; P = .045). Conclusion: Major loss of muscle mass but not body weight loss during preoperative chemotherapy is significantly associated with poor recurrence‐free survival after hepatectomy in patients with colorectal liver metastases. The mechanisms mediating this association may inform future trials on maintaining muscle mass with dedicated nutrition and exercise programs to improve outcomes.

Loss of muscle mass during preoperative chemotherapy predicts worse recurrence-free survival in patients with resectable colorectal liver metastases

MTA and 9.7% in the RFA group (p = 0.85). There was no mortality. Median hospital stay was 1 day for both groups. For the RFA vs MTA groups, local recurrence (LR) rate per lesion was 20.3% and 8.5%, respectively (p = 0.01). On Cox Proportion Hazards model, ablation modality was an independent predictor of LR following risk adjustment. Conclusion: To our knowledge, this is the first comparison of RFA and MTA in the treatment of CRLM. Our results demonstrates MTA achieves better local tumor control with shorter operative and ablation time.

Prognostic impact of perihepatic lymph node metastases in patients with resectable colorectal liver metastases

Although perihepatic lymph node metastases (PLNMs) are known to be a poor prognosticator for patients with colorectal liver metastases (CRLMs), optimal management remains unclear. This study aimed to determine the risk factors for PLNMs, and the survival impact of their number and location in patients with resectable CRLMs.

Oligometastases of Gastrointestinal Cancer Origin

a Department of General, Thoracic, Vascular and Transplantation Surgery, University of Rostock, Rostock, Germany; b Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany; c Department of General, Visceral and Transplant Surgery, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany; d University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany; e Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; f Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Humanitas Research Hospital, Rozzano (Milan), Italy

Long term outcome after resection of liver metastases from squamous cell carcinoma

BACKGROUND Squamous cell carcinoma (SCC) liver metastases still remains a difficult challenge and the effectiveness of resection for SCC liver metastases is unclear. The aim of this study was to analyze long-term outcomes of surgically treated patients with SCC liver metastases. METHODS The clinicopathological characteristics, overall survival (OS), and recurrence free survival (RFS) of all patients with SCC liver metastases resected between 1998 and 2015, were analyzed. RESULTS Among 28 patients who met inclusion criteria, there were 19 patients with anal cancer metastases (68%), 2 (7%) with cervix cancer metastases, 2 (7%) with tonsil cancer metastases, 2 (7%) with lung cancer metastases, 2 (7%) with primary unknown cancer metastases and 1 (4%) with vulvar cancer metastases. Four (14%) patients underwent major hepatectomy. There were no liver insufficiency cases or 90-day mortality. Cumulative 3- and 5-year OS rates were 52% and 47%. Cumulative 1- and 3-year RFS rates were 50% and 25%. CONCLUSIONS Long-term outcomes after resection of SCC liver metastases compare favorably with those of colorectal or neuroendocrine liver metastases. Liver resection can be an effective treatment option for SCC liver metastases in appropriately selected patients after systemic therapy.