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      Management of isolated para-aortic lymph node recurrence after surgery for colorectal cancer

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          Abstract

          Purpose

          The rare incidence of isolated para-aortic lymph node (PALN) recurrence of colorectal cancer has precluded the formulation of treatment guidelines. This study evaluated and compared the effects of different treatment modalities on survival outcomes in patients with PALN recurrence.

          Methods

          Patients diagnosed with isolated PALN recurrence after curative resection for primary colorectal cancer from January 2004 to December 2014 were evaluated retrospectively. Patients with isolated recurrence were selected using imaging modalities. Overall survival (OS) and survival after recurrence (SAR) were analyzed and compared between different treatments using the Kaplan-Meier method.

          Results

          The median OS was 64 months with a median follow-up time of 50 months. Of the 46 patients with PALN recurrence, 35 (76.1%) had isolated recurrences. Of these 35 patients, 16 underwent PALN resection and 19 received chemotherapy. Median SAR was significantly longer in patients who did than did not undergo resection (71 months vs. 39 months, P = 0.017). Median OS tended to be longer in patients who did than did not undergo resection (77 months vs. 62 months, P = 0.055). SAR was similar in patients who received radiotherapy and those who underwent resection (34 months vs. 46 months, P = 0.146). Three of 16 patients (18.8%) who underwent resection were found to be recurrence-free.

          Conclusion

          Surgical resection of isolated PALN recurrence may benefit patients, with favorable survival outcomes and by providing definitive diagnosis for proper treatment planning.

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          Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial

          Summary Background Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Methods This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% [95·66% CI 21·3–35·5] to 35·4% [28·1–42·7]; HR 0·79 [0·62–1·02]; p=0·058) in randomised patients; 8·1% (from 28·1% [21·2–36·6] to 36·2% [28·7–43·8]; HR 0·77 [0·60–1·00]; p=0·041) in eligible patients; and 9·2% (from 33·2% [25·3–41·2] to 42·4% [34·0–50·5]; HR 0·73 [0·55–0·97]; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Interpretation Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Funding Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.
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            Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

            Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.
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              Surgical resection of hepatic metastases from colorectal cancer: A systematic review of published studies

              No consensus on the indications for surgical resection of colorectal liver metastases exists. This systematic review has been undertaken to assess the published evidence for its efficacy and safety and to identify prognostic factors. Studies were identified by computerised and hand searches of the literature, scanning references and contacting investigators. The outcome measures were overall survival, disease-free survival, postoperative morbidity and mortality, quality of life and cost effectiveness, and a qualitative summary of the trends across all studies was produced. Only 30 of 529 independent studies met all the eligibility criteria for the review, and data on 30-day mortality and morbidity only were included from a further nine studies. The best available evidence came from prospective case series, but only two studies reported outcomes for all patients undergoing surgery. The remainder reported outcomes for selected groups of patients: those undergoing hepatic resection or those undergoing curative resection. Postoperative mortality rates were generally low (median 2.8%). The majority of studies described only serious postoperative morbidity, the most common being bile leak and associated perihepatic abscess. Approximately 30% of patients remained alive 5 years after resection and around two-thirds of these are disease free. The quality of the majority of published papers was poor and ascertaining the benefits of surgical resection of colorectal hepatic metastases is difficult in the absence of randomised trials. However, it is clear that there is group of patients with liver metastases who may become long-term disease- free survivors following hepatic resection. Such survival is rare in apparently comparable patients who do not have surgical treatment. Further work is needed to more accurately define this group of patients and to determine whether the addition of adjuvant treatments results in improved survival.
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                Author and article information

                Journal
                Ann Surg Treat Res
                Ann Surg Treat Res
                ASTR
                Annals of Surgical Treatment and Research
                The Korean Surgical Society
                2288-6575
                2288-6796
                March 2020
                28 February 2020
                : 98
                : 3
                : 130-138
                Affiliations
                [1 ]Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
                [2 ]Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
                [3 ]Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
                [4 ]Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
                Author notes
                Corresponding Author: In Ja Park. Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Tel: +82-2-3010-3937, Fax: +82-2-474-9027, ipark@ 123456amc.seoul.kr
                Author information
                https://orcid.org/0000-0001-5355-3969
                Article
                10.4174/astr.2020.98.3.130
                7052390
                99e8c222-8134-4dd1-b66c-d45c0bb8a489
                Copyright © 2020, the Korean Surgical Society

                Annals of Surgical Treatment and Research is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 August 2019
                : 14 November 2019
                : 04 January 2020
                Funding
                Funded by: Asan Institute for Life Sciences, Asan Medical Center, CrossRef https://doi.org/10.13039/501100005006;
                Award ID: 2016-729
                Categories
                Original Article

                colorectal neoplasms,lymph node excision,mortality,para-aortic lymph node

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