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Background: In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood., Methods: A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed., Results: 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy., Conclusion: Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases., (© 2024 Published by Elsevier Ltd.)

Background: Consensus on the best surgical strategy for the management of synchronous colorectal liver metastases (sCRLM) has not been achieved. This study aimed to assess the attitudes of surgeons involved in the treatment of sCRLM., Methods: Surveys designed for colorectal, hepato-pancreato-biliary (HPB), and general surgeons were disseminated through representative societies. Subgroup analyses were performed to compare responses between specialties and continents., Results: Overall, 270 surgeons (57 colorectal, 100 HPB and 113 general surgeons) responded. Specialist surgeons more frequently utilized minimally invasive surgery (MIS) than general surgeons for colon (94.8% vs. 71.7%, p < 0.001), rectal (91.2% vs. 64.6%, p < 0.001), and liver resections (53% vs. 34.5%, p = 0.005). In patients with an asymptomatic primary, the liver-first two-stage approach was preferred in most respondents' centres (59.3%), while the colorectal-first approach was preferred in Oceania (83.3%) and Asia (63.4%). A substantial proportion of the respondents (72.6%) had personal experience with minimally invasive simultaneous resections, and an expanding role for this procedure was foreseen (92.6%), while more evidence was desired (89.6%). Respondents were more reluctant to combine a hepatectomy with low anterior (76.3%) and abdominoperineal resections (73.3%), compared to right (94.4%) and left hemicolectomies (90.7%). Colorectal surgeons were less inclined to combine right or left hemicolectomies with a major hepatectomy than HPB and general surgeons (right: 22.8% vs. 50% and 44.2%, p = 0.008; left: 14% vs. 34% and 35.4%, p = 0.002, respectively)., Conclusion: The clinical practices and viewpoints on the management of sCRLM differ between continents, and between and within surgical specialties. However, there appears to be consensus on a growing role for MIS and a need for evidence-based input., (© 2023. The Author(s).)

Background: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes., Methods: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression., Results: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013)., Conclusions: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Textbook outcome (TO) is a composite measure that captures the most desirable surgical outcomes as a single indicator, yet to date TO has not been defined and assessed in the field of laparoscopic liver resection (LLR) and open liver resection (OLR)., Objective: To obtain international agreement on the definition of TO in liver surgery (TOLS) and to assess the incidence of TO in LLR and OLR in a large international multicenter database using a propensity-score matched analysis., Design, Setting, and Participants: Patients undergoing LLR or OLR for all liver diseases between January 2011 and October 2019 were analyzed using a large international multicenter liver surgical database. An international survey was conducted among all members of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) and International Hepato-Pancreato-Biliary Association (IHPBA) to reach agreement on the definition of TOLS. The rate of TOLS was assessed for LLR and OLR before and after propensity-score matching. Factors associated with achieving TOLS were investigated., Main Outcomes and Measures: Textbook outcome, with TOLS defined as the absence of intraoperative incidents of grade 2 or higher, postoperative bile leak grade B or C, severe postoperative complications, readmission within 30 days after discharge, in-hospital mortality, and the presence of R0 resection margin., Results: A total of 8188 patients (4559 LLR; median age, 65 years [interquartile range, 55-73 years]; 2529 were male [55.8%] and 3629 OLR; median age, 64 years [interquartile range, 56-71 years]; 2204 were male [60.7%]) were included in the analysis of whom 69.1% achieved TOLS; 74.8% for LLR and 61.9% for OLR (P < .001). On multivariable analysis, American Society of Anesthesiologists grade III, previous abdominal surgery, histological diagnosis of colorectal liver metastases (odds ratio [OR], 0.656 [95% CI, 0.457-0.940]; P = .02), cholangiocarcinoma, non-CRLM, a tumor size of 30 mm or more, minor resection of posterior/superior segments (OR, 0.716 [95% CI, 0.577-0.887]; P = .002), anatomically major resection (OR, 0.579 [95% CI, 0.418-0.803]; P = .001), and nonanatomical resection (OR, 0.612 [95% CI, 0.476-0.788]; P < .001) were associated with a worse TOLS rate after LLR. For OLR, only histological diagnosis of cholangiocarcinoma (OR, 0.360 [95% CI, 0.214-0.607]; P < .001) and a tumor size of 30 mm or more (30-50 mm = OR, 0.718 [95% CI, 0.565-0.911]; P = .01; 50.1-100 mm = OR, 0.729 [95% CI, 0.554-0.960]; P = .02; >10 cm = OR, 0.550 [95% CI, 0.366-0.826]; P = .004) were associated with a worse TOLS rate., Conclusions and Relevance: In this multicenter study, TOLS was found to be a useful tool for assessing patient-level hospital performance and may have utility in optimizing patient outcomes after LLR and OLR.

Background: Hepatectomy for initially unresectable colorectal liver metastases (IU-CLM) is considered at high risk due to the extensive preoperative chemotherapy (CHT) and complex surgical procedures required, and its results are questioned due to frequent and early post-operative recurrence. We aim to compare patients with initially resectable CLM (IR-CLM) and IU-CLM and identify prognostic factors among IU-CLM patients., Methods: A total of 81 patients with IU-CLM, undergoing hepatectomy following conversion CHT, were compared to 526 IR-CLM patients. Predictors of overall (OS) and disease-free survival (DFS) were identified for IU-CLM patients., Results: Patients resected for IU-CLM, compared to IR-CLM, had more and larger CLM and more frequently underwent prolonged CHT and major/extended hepatectomy (P < 0.001 for all comparisons). Such characteristics paralleled higher rates of overall and major (Clavien-Dindo ≥3) complications, longer median post-operative length of stay and lower 5-year survival rates (P < 0.001 for all comparisons) among IU-CLM patients compared to IR-CLM, with similar mortality (1.2% and nil for IU-CLM and IR-CLM, respectively). Among IU-CLM patients, 62 with partial response to CHT (versus tumour stability according to the Response Evaluation Criteria in Solid Tumors criteria) had better DFS (hazard ratio 2.76, P = 0.001) and OS (hazard ratio 2.83, P =  0.002), and their 5-year survival rates (DFS 19.8%, OS 46.7%) approached those of IR-CLM patients (DFS 31%, OS 59%, P > 0.05 for both comparisons)., Conclusion: Resection of IU-CLM has acceptable perioperative results. Tumour responsiveness to conversion CHT improves IU-CLM patient selection for hepatectomy., (© 2020 Royal Australasian College of Surgeons.)

Introduction: Previous studies have suggested that the use of regional anesthesia can reduce recurrence risk after oncologic surgery. The purpose of this study was to assess the effect of epidural anesthesia on recurrence-free (RFS) and overall survival (OS) after hepatic resection for colorectal liver metastases (CLM)., Methods: After approval of the institutional review board, the records of all adult patients who underwent elective hepatic resection between January 2006 and October 2011 were retrospectively reviewed. Patients were categorized according to use of perioperative epidural analgesia versus intravenous analgesia. Univariate and multivariate analyses were performed to identify factors influencing RFS and OS., Results: Of 510 total patients, 390 received epidural analgesia (EA group) and 120 patients received intravenous analgesia (IVA group). Compared with the IVA group, more patients in the EA group underwent associated surgical procedures with consequently longer operative times (p < 0.001). In addition, the EA group received more intraoperative fluids and had higher urine output volumes (p ≤ 0.001). Five-year RFS was longer in the EA group (34.7%) compared with the IVA group (21.1%). On multivariate analysis, the receipt of epidural analgesia was an independent predictor of improved RFS (p = 0.036, hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.56-0.95), but not OS (p = 0.102, HR 0.72; 95% CI 0.49-1.07)., Conclusions: This study suggests an association between epidural analgesia and improved RFS, but not OS, after CLM resection. These results warrant further prospective, randomized studies on the benefits of regional anesthesia on oncologic outcomes after hepatic resection for CLM.

Background: RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM., Methods: RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2)., Results: Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9%, respectively) than in patients with RAS mutations (10.5 and 36.8%; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95% CI 1.45-13.15] and major pathologic response (OR, 2.61; 95% CI 1.17-5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy., Conclusions: RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy.

Background: After cancer surgery, complications, and disability prevent some patients from receiving subsequent treatments. Given that an inability to complete all intended cancer therapies might negate the oncologic benefits of surgical therapy, strategies to improve return to intended oncologic treatment (RIOT), including minimally invasive surgery (MIS), are being investigated., Methods: This project was designed to evaluate liver tumor patients to determine the RIOT rate, risk factors for inability to RIOT, and its impact on survivals. Outcomes for a homogenous cohort of 223 patients who underwent open-approach surgery for metachronous colorectal liver metastases and a group of 27 liver tumor patients treated with MIS hepatectomy were examined., Results: Of the 223 open-approach patients, 167 were offered postoperative therapy, yielding a RIOT rate of 75%. The remaining 56 (25%) patients were unable to receive further treatment due to surgical complications (n = 29 pts) or poor performance status (n = 27 pts). Risk factors associated with inability to RIOT were hypertension (OR 2.2, P = 0.025), multiple preoperative chemotherapy regimens (OR 5.9, P = 0.039), and postoperative complications (OR 2.0, P = 0.039). Inability to RIOT correlated with shorter disease-free and overall survivals (P < 0.001, HR = 2.16; and P = 0.005, HR = 2.07, respectively). In contrast to the open surgery group, 100% of MIS patients who were intended to initiate postoperative therapy did so (P = 0.038) within a shorter median time interval (MIS: 15 days vs. open: 42 days; P < 0.001)., Conclusions: The relationship between RIOT and long-term oncologic outcomes suggests that RIOT rates for both open- and MIS-approach cancer surgery should routinely be reported as a quality indicator., (© 2014 Wiley Periodicals, Inc.)

Background: Most patients requiring an extended right hepatectomy (ERH) have an inadequate standardized future liver remnant (sFLR) and need preoperative portal vein embolization (PVE). However, the clinical and oncological impact of PVE in such patients remains unclear., Methods: All consecutive patients presenting at the M. D. Anderson Cancer Center with colorectal liver metastases (CLM) requiring ERH at presentation from 1995 to 2012 were studied. Surgical and oncological outcomes were compared between patients with adequate and inadequate sFLRs at presentation., Results: Of the 265 patients requiring ERH, 126 (47·5 per cent) had an adequate sFLR at presentation, of whom 123 underwent a curative resection. Of the 139 patients (52·5 per cent) who had an inadequate sFLR and underwent PVE, 87 (62·6 per cent) had a curative resection. Thus, the curative resection rate was increased from 46·4 per cent (123 of 265) at baseline to 79·2 per cent (210 of 265) following PVE. Among patients who underwent ERH, major complication and 90-day mortality rates were similar in the no-PVE and PVE groups (22·0 and 4·1 per cent versus 31 and 7 per cent respectively); overall and disease-free survival rates were also similar in these two groups. Of patients with an inadequate sFLR at presentation, those who underwent ERH had a significantly better median overall survival (50·2 months) than patients who had non-curative surgery (21·3 months) or did not undergo surgery (24·7 months) (P = 0·002)., Conclusion: PVE enabled curative resection in two-thirds of patients with CLM who had an inadequate sFLR and were unable to tolerate ERH at presentation. Patients who underwent curative resection after PVE had overall and disease-free survival rates equivalent to those of patients who did not need PVE., (© 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.)

Background: The present study was designed to evaluate the role of intraoperative ultrasound (IOUS) in intrahepatic staging and the impact on surgical strategy for patients with colorectal liver metastases (CRLM)., Methods: The study included 515 patients who had undergone liver resection for CRLM at two tertiary care referral centers. Data from a prospectively collected database were retrospectively analysed. Early intrahepatic recurrence was assessed at 3 and 6 months after resection and was considered as residual disease undetected by IOUS. Performance of imaging modalities was compared by analysis of studies on individual patients., Results: A total of 1,370 liver metastases were detected preoperatively with a median of 3 imaging modalities. MRI and PET were performed in 51 and 42 % of the patients, respectively. Median number of days between last imaging and surgery was 18. Contrast-enhanced IOUS was performed in 136 patients (26.4 %). Intraoperatively, 293 new nodules were found in 132 patients: on histology 280 were CRLM (17.6 %). Surgical strategy was changed in 140 patients (27.2 %). On multivariate analysis synchronous and bilobar metastases ≥ 3 in number, BMI ≥ 30, and time between last imaging and surgery longer than 18 days resulted in predictive factors indicating new nodules detected by IOUS. Early intrahepatic recurrences were 3.7 and 7.9 % at 3 and 6 months. Performance of CT, MRI, FDG-PET, and intraoperative staging was compared: sensitivity was 63.6, 68.8, 53.6, and 92 % and specificity was 91, 92.3, 95.8, and 97.8 %, respectively, Conclusions: The use of IOUS continues to be mandatory for correct staging of patients with CRLM undergoing liver resection.

Objective: To determine the impact of RAS mutation status on survival and patterns of recurrence in patients undergoing curative resection of colorectal liver metastases (CLM) after preoperative modern chemotherapy., Background: RAS mutation has been reported to be associated with aggressive tumor biology. However, the effect of RAS mutation on survival and patterns of recurrence after resection of CLM remains unclear., Methods: Somatic mutations were analyzed using mass spectroscopy in 193 patients who underwent single-regimen modern chemotherapy before resection of CLM. The relationship between RAS mutation status and survival outcomes was investigated., Results: Detected somatic mutations included RAS (KRAS/NRAS) in 34 (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%) patients. At a median follow-up of 33 months, 3-year overall survival (OS) rates were 81% in patients with wild-type versus 52.2% in patients with mutant RAS (P = 0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild-type versus 13.5% with mutant RAS (P = 0.001). Liver and lung recurrences were observed in 89 and 83 patients, respectively. Patients with RAS mutation had a lower 3-year lung RFS rate (34.6% vs 59.3%, P < 0.001) but not a lower 3-year liver RFS rate (43.8% vs 50.2%, P = 0.181). In multivariate analyses, RAS mutation predicted worse OS [hazard ratio (HR) = 2.3, P = 0.002), overall RFS (HR = 1.9, P = 0.005), and lung RFS (HR = 2.0, P = 0.01), but not liver RFS (P = 0.181)., Conclusions: RAS mutation predicts early lung recurrence and worse survival after curative resection of CLM. This information may be used to individualize systemic and local tumor-directed therapies and follow-up strategies.

Background: To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM)., Methods: One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response-defined as the proportion of tumor cells remaining (complete, 0%; major, <50%; minor, ≥50%) and tumor thickness at the tumor-normal liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, ≥5 mm)-was assessed by a central pathology reviewer and local pathologists., Results: Pathologic response was complete in 8% of patients, major in 49% of patients, and minor in 43% of patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm in 56% of patients, and ≥5 mm in 23% of patients. On multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P = .002, .009), tumor thickness at TNI (P = 0.015, <.001), duration of preoperative chemotherapy (P = .028, .043), number of CLM (P = .038, . 037), and margin (P = .011, .016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P = .004, .015), duration of preoperative chemotherapy (P = .025), number of nodules (P = .027), and margin (P = .014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ = .82) and substantial agreement (κ = .76) for tumor thickness between the central reviewer and local pathologists., Conclusions: Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM., (Copyright © 2013 American Cancer Society.)

Objective: To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy., Background: In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial., Methods: Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy., Results: Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587)., Conclusions: In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy.

Purpose: The purposes of this study were to confirm the prognostic value of an optimal morphologic response to preoperative chemotherapy in patients undergoing chemotherapy with or without bevacizumab before resection of colorectal liver metastases (CLM) and to identify predictors of the optimal morphologic response., Patients and Methods: The study included 209 patients who underwent resection of CLM after preoperative chemotherapy with oxaliplatin- or irinotecan-based regimens with or without bevacizumab. Radiologic responses were classified as optimal or suboptimal according to the morphologic response criteria. Overall survival (OS) was determined, and prognostic factors associated with an optimal response were identified in multivariate analysis., Results: An optimal morphologic response was observed in 47% of patients treated with bevacizumab and 12% of patients treated without bevacizumab (P < .001). The 3- and 5-year OS rates were higher in the optimal response group (82% and 74%, respectively) compared with the suboptimal response group (60% and 45%, respectively; P < .001). On multivariate analysis, suboptimal morphologic response was an independent predictor of worse OS (hazard ratio, 2.09; P = .007). Receipt of bevacizumab (odds ratio, 6.71; P < .001) and largest metastasis before chemotherapy of ≤ 3 cm (odds ratio, 2.12; P = .025) were significantly associated with optimal morphologic response. The morphologic response showed no specific correlation with conventional size-based RECIST criteria, and it was superior to RECIST in predicting major pathologic response., Conclusion: Independent of preoperative chemotherapy regimen, optimal morphologic response is sufficiently correlated with OS to be considered a surrogate therapeutic end point for patients with CLM.

Objective: We hypothesized that metachronous colorectal liver metastases (CLM) have different biology after failure of oxaliplatin (FOLFOX) compared to 5-fluorouracil (5-FU) or no chemotherapy for adjuvant treatment of colorectal cancer (CRC)., Background: It is unclear whether patients treated with liver resection for metachronous CLM after adjuvant FOLFOX for CRC have worse outcomes than those who received 5-FU or no chemotherapy., Methods: We identified 341 patients who underwent hepatectomy for metachronous CLM (disease-free interval ≥12 months, 1993-2010). Mass-spectroscopy genotyping for somatic gene mutations in CLM was performed in a subset of 129 patients., Results: Adjuvant treatment for primary CRC was FOLFOX in 77 patients, 5-FU in 169 patients, and no chemotherapy in 95 patients. Node-positive primary was comparable between FOLFOX and 5-FU but lower in the no-chemotherapy group (P < 0.0001). Median metastasis size was smaller in the FOLFOX group (2.5 cm) than in the 5-FU (3.0 cm) or no-chemotherapy (3.5 cm) groups, (P = 0.008) although prehepatectomy chemotherapy utilization, metastases number, and carcinoembryonic antigen levels were similar. Disease-free survival (DFS) and overall survival (OS) rates after hepatectomy were worse in patients treated with adjuvant FOLFOX [DFS at 3 years: 14% vs 38% (5-FU) vs 45% (no-chemo), OS at 3 years: 58% vs 70% (5-FU) vs 84% (no-chemo)]. On multivariate analysis, adjuvant FOLFOX was associated with worse DFS (P < 0.0001) and OS (P < 0.0001). Mutation analysis revealed ≥1 mutations in 57% of patients (27/47) after FOLFOX, 29% (12/41) after 5-FU, and 32% (13/41) after no chemotherapy (P = 0.011)., Conclusions: Adjuvant FOLFOX for primary CRC is associated with a high rate of somatic mutations in liver metastases and inferior outcomes after hepatectomy for metachronous CLM.

Background: The aim of the present study is to examine the effect of systemic chemotherapy after the 1st-stage hepatectomy (CT×2) on the progression of disease and dropout rates. A major pitfall of the 2-stage hepatectomy procedure is a high dropout rate after the 1st-stage hepatectomy due to progression of disease (PD). Routine use of CT×2 has been advocated., Methods: A total of 47 patients with multiple, bilateral unresectable liver metastases were selected for a 2-stage hepatectomy procedure (±portal vein occlusion)., Results: Of the total, 37 patients (78.7%) underwent systemic chemotherapy before the 1st-stage hepatectomy (CT×1) and 25 patients (53.2%) underwent CT×2; PD was significantly more common during CT×2 than during CT×1 (P=.002). Of the 47 patients planned for the 2nd-stage hepatectomy, 36 (76.6%) completed the procedure. Of these 47 patients, 25 (53.2%) showed PD after the 1st-stage hepatectomy, 12 in the CT×2 group and 13 in the no-CT×2 group; administration of CT×2 did not significantly affect the PD rate (P=.561). The overall dropout rate was 23.4% (n=11 patients): 16% in the CT×2 group vs. 31.8% in the no-CT×2 group (P=.303)., Conclusions: The routine use of chemotherapy between the 1st- and 2nd-stage hepatectomy does not guarantee lower PD and dropout rates.

Background: Optimal margin width is uncertain because of conflicting results from recent studies using overall survival as the end-point. After recurrence, re-resection and aggressive chemotherapy heavily affect survival time; the potential confounding effect of such factors has not been investigated. Use of recurrence-free survival (RFS) may overcome this limitation. The aim of this study is to evaluate the impact of width of resection margin on RFS and site of recurrence after hepatic resection for colorectal metastases (CRM)., Methods: From a prospectively maintained institutional database (1/1999-12/2007) we identified 314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed pathologic analysis of the surgical margin and complete follow-up imaging studies documenting disease status and site of recurrence, which was categorized as: resection margin (M(arg)), other intra-hepatic ((other)IH), lung (L) or other extra-hepatic ((other)EH). Recurrence-free estimation was the survival end-point., Results: Median follow-up was 56.5 months. Two hundred and fifteen patients (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection margin was associated with an increased risk of M(arg) recurrence (P < 0.001). The presence of >or=2 metastases was the only factor increasing the risk of positive margins (P < 0.05). The width of the negative resection margin (>or=1 cm versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P = 0.6). Node status of the primary tumour, and size and number of CRM were independent predictors of RFS., Conclusions: Tumour biology and not the width of the negative resection margin affect RFS.