E. Simoneau

Surgical Resection for Recurrence After Two-Stage Hepatectomy for Colorectal Liver Metastases Is Feasible, Is Safe, and Improves Survival

BackgroundRecurrence rates are high for patients who have undergone two-stage hepatectomy (TSH) for bilateral colorectal liver metastases, and there is no established treatment approach for recurrent disease. This study aimed to determine the feasibility, safety, and prognostic impact of surgical resection for recurrence after TSH and the prognostic role of RAS mutation in this cohort.MethodsThe study included 137 patients intended to undergo TSH for bilateral colorectal metastases during 2003–2016. Clinicopathologic factors were compared using univariate and multivariate analyses.ResultsOne hundred eleven patients (81%) completed TSH. The median recurrence-free survival in these patients was 12xa0months. Of the 83 patients with subsequent recurrence, 31 (37%) underwent resection for recurrence, and 11 underwent multiple resections for recurrence. Forty-eight operations were performed for recurrence: 23 repeat hepatectomies, 14 pulmonary resections, 5 locoregional resections, and 6 concurrent resections in multiple organ sites. The median overall survival (OS) among patients with recurrence was 143xa0months for patients who underwent resection and 49xa0months for those who did not (Pu2009<u20090.001). On multivariate analysis, resection for recurrence (hazard ratio [HR] 0.25; 95% CI 0.10–0.54, Pu2009<u20090.001) was associated with better OS, whereas RAS mutation (HR 2.25; 95% CI 1.16–4.50, Pu2009=u20090.016) and first recurrence in multiple sites (HR 2.28; 95% CI 1.17–4.37, Pu2009=u20090.016) were independent predictors of worse overall survival.ConclusionsIn patients who have undergone TSH for bilateral colorectal liver metastases, recurrence is frequent and should be treated with resection whenever possible. Patients with wild-type RAS fare particularly well with resection for recurrence.

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.

Minimally invasive management of the entire treatment sequence in patients with stage IV colorectal cancer: a propensity-score weighting analysis

BACKGROUNDnIn patients with stage IV colorectal cancer (CRC), minimally invasive surgery (MIS) may offer optimal oncologic outcome with low morbidity. However, the relative benefit of MIS compared to open surgery in patients requiring multistage resections has not been evaluated.nnnMETHODSnPatients who underwent totally minimally invasive (TMI) or totally open (TO) resections of CRC primary and liver metastases (CLM) in 2009-2016 were analyzed. Inverse probability of weighted adjustment by propensity score was performed before analyzing risk factors for complications and survival.nnnRESULTSnThe study included 43 TMI and 121 TO patients. Before and after adjustment, TMI patients had significantly less cumulated postoperative complications (41% vs. 59%, p = 0.001), blood loss (median 100 vs. 200 ml, p = 0.001) and shorter length of hospital stay (median 4.5 vs. 6.0 days, p < 0.001). Multivariate analysis identified TO approach vs. MIS (OR = 2.4, p < 0.001), major liver resection (OR = 4.4, p < 0.001), and multiple CLM (OR = 2.3, p = 0.001) as independent risk factors for complications. 5-year overall survival was comparable (81% vs 68%, p = 0.59).nnnCONCLUSIONnIn patients with CRC undergoing multistage surgical treatment, MIS resection contributes to optimal perioperative outcomes without compromise in oncologic outcomes.

Progression of Colorectal Cancer Liver Metastasis After Chemotherapy: A New Test of Time?

With the increasing use of chemotherapy prior to resection for colorectal liver metastases (CLM), progression on treatment has been used at some hepatobiliary centers as a criterion to determine whether resection was justified. In 2004, Adam et al. reported the outcomes of patients exhibiting disease progression during preoperative chemotherapy in a series of 131 resected patients with C 4 metastases and showed 5-year survival of only 8% for this subgroup. This led to the conclusion that disease progression during preoperative chemotherapy may represent a contraindication to resection due to lack of survival benefit. Subsequently, the same authors later softened their recommendations and showed in a series using LiverMetSurvey data that disease progression only, although a negative prognostic factor, was associated with 5-year survival of 53%. In that study of 2146 patients of whom 8% (n = 176) progressed during preoperative chemotherapy, presence of additional prognostic factors [size[ 50 mm,[ 3 lesions, carcinoembryonic antigen (CEA)[ 200 ng/mL] contributed to adverse outcomes in that subset of patients, with high CEA being independently associated with worse outcome [relative risk (RR) 5.06 (1.72–14.95), p = 0.003] with 10% 3-year overall survival. In the current issue of Annals of Surgical Oncology, Vigano et al. further address the issue of tumor control in the preoperative period in a study focusing on the time interval off preoperative chemotherapy prior to resection. The authors report the outcomes of 128 patients who were resected after an initial (stable or partial) response to preoperative chemotherapy. All patients included were imaged three times, including before and after chemotherapy and prior to resection ([ 4 weeks after chemotherapy cessation). Using Response Evaluation Criteria in Solid Tumors (RECIST) measurement, Vigano et al. report that 25% (n = 32) had disease progression in the interval between chemotherapy and resection. After stratification by different time intervals off treatment, the group with worse outcome consisted of a small subset of patients (n = 8) who progressed within a short time interval off systemic therapy ( 8 weeks), with no survivors at 2 years, compared with 2-year overall survival (OS) of 52.4% for patients with stable disease. As the time interval increased, the survival gap between patients with progression versus stable disease became narrower (3-year OS 25.0% vs. 53.7%, p = 0.009), until no differences in outcomes were found for longer ([ 16 weeks) time intervals off chemotherapy (3-year OS 37.5% vs. 48.5%, p = 0.288, progression versus stable disease, respectively). The authors concluded that disease progression upon cessation of preoperative chemotherapy may be a contraindication to surgery given the markedly poor outcomes. The authors rightly focused on short time intervals off treatment, and their study emphasizes the need to perform preresection imaging to risk-stratify patients and reevaluate the disease after cessation of preoperative therapy. A shortcoming of the study is the lack of denominator, as patients who progressed to the point of unresectability were not included in the study. Additionally, the authors focus on liver progression, whereas we feel that new intraand extrahepatic disease is as equally if not more concerning than hepatic progression of known hepatic disease. In addition to the relatively small number of patients in the series, an issue with the study of Vigano et al. is the disease assessment by RECIST, which is known to have some limitations and no association with survival especially in Society of Surgical Oncology 2018With the increasing use of chemotherapy prior to resection for colorectal liver metastases (CLM), progression on treatment has been used at some hepatobiliary centers as a criterion to determine whether resection was justified. In 2004, Adam et al. reported the outcomes of patients exhibiting disease progression during preoperative chemotherapy in a series of 131 resected patients with C 4 metastases and showed 5-year survival of only 8% for this subgroup. This led to the conclusion that disease progression during preoperative chemotherapy may represent a contraindication to resection due to lack of survival benefit. Subsequently, the same authors later softened their recommendations and showed in a series using LiverMetSurvey data that disease progression only, although a negative prognostic factor, was associated with 5-year survival of 53%. In that study of 2146 patients of whom 8% (n = 176) progressed during preoperative chemotherapy, presence of additional prognostic factors [size[ 50 mm,[ 3 lesions, carcinoembryonic antigen (CEA)[ 200 ng/mL] contributed to adverse outcomes in that subset of patients, with high CEA being independently associated with worse outcome [relative risk (RR) 5.06 (1.72–14.95), p = 0.003] with 10% 3-year overall survival. In the current issue of Annals of Surgical Oncology, Vigano et al. further address the issue of tumor control in the preoperative period in a study focusing on the time interval off preoperative chemotherapy prior to resection. The authors report the outcomes of 128 patients who were resected after an initial (stable or partial) response to preoperative chemotherapy. All patients included were imaged three times, including before and after chemotherapy and prior to resection ([ 4 weeks after chemotherapy cessation). Using Response Evaluation Criteria in Solid Tumors (RECIST) measurement, Vigano et al. report that 25% (n = 32) had disease progression in the interval between chemotherapy and resection. After stratification by different time intervals off treatment, the group with worse outcome consisted of a small subset of patients (n = 8) who progressed within a short time interval off systemic therapy ( 8 weeks), with no survivors at 2 years, compared with 2-year overall survival (OS) of 52.4% for patients with stable disease. As the time interval increased, the survival gap between patients with progression versus stable disease became narrower (3-year OS 25.0% vs. 53.7%, p = 0.009), until no differences in outcomes were found for longer ([ 16 weeks) time intervals off chemotherapy (3-year OS 37.5% vs. 48.5%, p = 0.288, progression versus stable disease, respectively). The authors concluded that disease progression upon cessation of preoperative chemotherapy may be a contraindication to surgery given the markedly poor outcomes. The authors rightly focused on short time intervals off treatment, and their study emphasizes the need to perform preresection imaging to risk-stratify patients and reevaluate the disease after cessation of preoperative therapy. A shortcoming of the study is the lack of denominator, as patients who progressed to the point of unresectability were not included in the study. Additionally, the authors focus on liver progression, whereas we feel that new intraand extrahepatic disease is as equally if not more concerning than hepatic progression of known hepatic disease. In addition to the relatively small number of patients in the series, an issue with the study of Vigano et al. is the disease assessment by RECIST, which is known to have some limitations and no association with survival especially in Ann Surg Oncol (2018) 25:1469–1470 https://doi.org/10.1245/s10434-018-6439-0