Oriana Ciacio

PURPOSE: Although oncosurgical strategies have demonstrated increased survival in patients with unresectable colorectal liver metastases (CLM), their potential for cure is still questioned. The aim of this study was to evaluate long-term outcome after combining downsizing chemotherapy and rescue surgery and to define prognostic factors of cure. PATIENTS AND METHODS: All patients with initially unresectable CLM who underwent rescue surgery and had a minimum follow-up of 5 years were included. Cure was defined as a disease-free interval > or = 5 years from last hepatic or extrahepatic resection until last follow-up. RESULTS: Mean age of 184 patients who underwent resection (April 1988 through July 2002) was 56.9 years. Patients had a mean number of 5.3 metastases (bilobar in 76%), associated to extrahepatic disease in 27%. Surgery was possible after one (74%) or more (26%) lines of chemotherapy. Five- and 10-year overall survival rates were 33% and 27%, respectively. Of 148 patients with a follow-up > or = 5 years, 24 patients (16%) were considered cured (mean follow-up, 118.6 months), six (25%) of whom were considered cured after repeat resection of recurrence. Twelve "cured" patients (50%) had a disease-free interval more than 10 years. Cured patients more often had three or fewer metastases less than 30 mm (P = .03) responding to first-line chemotherapy (P = .05). Multivariate analysis identified maximum size of metastases less than 30 mm at diagnosis, number of metastases at hepatectomy three or fewer, and complete pathologic response as independent predictors of cure. CONCLUSION: Cure can be achieved overall in 16% of patients with initially unresectable CLM resected after downsizing chemotherapy. In addition to increased survival, this oncosurgical approach has real potential for disease eradication.

Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post‐LT 1‐year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm 2 (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm 2 (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One‐ and 5‐year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively ( P < 0.001). In conclusion, pre‐LT PMA is a simple tool to assess sarcopenia. We established sex‐specific cutoff values (1561 mm 2 in men, 1464 mm 2 in women) in a cirrhotic population and showed that 1‐year survival was significantly poorer in sarcopenic patients. Liver Transplantation 23 143–154 2017 AASLD

BACKGROUND: Data on recurrence patterns following hepatectomy for colorectal liver metastases (CRLMs) and their impact on long-term outcomes are limited in the setting of modern multimodal management. This study sought to characterize the patterns of, factors associated with, and survival impact of recurrence following initial hepatectomy for CRLMs. METHODS: A retrospective cohort study of patients undergoing initial hepatectomy for CRLMs at 39 institutions (2006-2013) was conducted. Kaplan-Meier methods were used for survival analyses. Overall survival landmark analysis at 12 months after hepatectomy was performed to compare groups based on recurrence. Multivariable Cox and regression models were used to determine factors associated with recurrence. RESULTS: Among 2320 patients, tumours recurred in 47·4 per cent at median of 10·1 (range 0-88) months; 89·1 per cent of recurrences developed within 3 years. Recurrence was intrahepatic in 46·2 per cent, extrahepatic in 31·8 per cent and combined intra/extrahepatic in 22·0 per cent. The 5-year overall survival rate decreased from 74·3 (95 per cent c.i. 72·2 to 76·4) per cent without recurrence to 57·5 (55·0 to 60·0) per cent with recurrence (adjusted hazard ratio (HR) 3·08, 95 per cent c.i. 2·31 to 4·09). After adjusting for clinicopathological variables, prehepatectomy factors associated with increased risk of recurrence were node-positive primary tumour (HR 1·27, 1·09 to 1·49), more than three liver metastases (HR 1·27, 1·06 to 1·52) and largest metastasis greater than 4 cm (HR 1·19; 1·01 to 1·43). CONCLUSION: Recurrence after CRLM resection remains common. Although overall survival is inferior with recurrence, excellent survival rates can still be achieved.

BACKGROUND: Regenerative nodular hyperplasia (RNH) represents the end-stage of vascular lesions of the liver induced by chemotherapy. The goal was to evaluate its incidence and impact on the outcome of patients resected for colorectal liver metastases (CLM). METHODS: Patients who underwent hepatectomy for CLM after six cycles or more of first-line chemotherapy, between January 1990 and November 2006, were included. Detailed histopathologic analysis of the nontumoral liver was performed according to a standard format. RESULTS: From a cohort of 856 resected patients at our institution, 771 (90%) received preoperative chemotherapy. Of these, 146 fulfilled the selection criteria and were included: 24 (16%) received 5-fluorouracil (5-FU) and leucovorin (LV) alone, 92 (63%) had 5-FU/LV and oxaliplatin, 18 (12%) had 5-FU/LV and irinotecan, and 12 (8%) were treated by 5-FU/LV, oxaliplatin, and irinotecan. RNH occurred in 22 of 146 patients (15%). Twenty of these patients (91%) received oxaliplatin, of whom six (30%) had chronomodulated therapy. Patients treated by oxaliplatin more often had RNH compared with oxaliplatin-naïve patients (22 vs. 4%). Although operative mortality was nil, the presence of RNH was associated with increased postoperative hepatic morbidity (50 vs. 29%). Elevated preoperative gamma-glutamyltransferase (GGT) (>80 U/L; >1N) and total bilirubin levels (>15 μmol/L; >1N) were independent predictors of RNH. CONCLUSIONS: Patients with CLM who receive preoperative oxaliplatin have an increased risk of RNH and associated postoperative morbidity. Increased serum GGT and bilirubin are useful markers to predict the presence of RNH.