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Efficacy of neoadjuvant chemotherapy for initially resectable colorectal liver metastases:A retrospective cohort study

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World Journal of Gastrointestinal Oncology 2022年第7期14卷 1281-1294页

作者： Kazuhisa Takeda Yu Sawada Yasuhiro Yabushita Yuki Honma takafumi kumamoto Jun Watanabe Ryusei Matsuyama Chikara Kunisaki Toshihiro Misumi Itaru Endo Gastroenterological Center Yokohama City University Medical CenterYokohama 232-0024Japan Department of Gastroenterological Surgery Yokohama City University Graduate School of MedicineYokohama 236-0004Jordan Department of Biostatistics Yokohama City University Graduate School of MedicineYokohama 236-0004Japan

BACKGROUND The liver is the most common metastatic site of colorectal cancer.Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases(CRLMs).However,there are cases of early recurrence after upfront hepatectomy alone.In selected high-risk patients,neoadjuvant chemotherapy(NAC)may improve longterm survival.AIM To determine the efficacy of NAC for initially resectable CRLMs.METHODS Among 644 patients who underwent their first hepatectomy for CRLMs at our institution,297 resectable cases were stratified into an upfront hepatectomy group(238 patients)and a NAC group(59 patients).Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression analysis.Propensity score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups,according to the number of poor prognostic factors.Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS Preoperative carcinoembryonic antigen levels(≥10 ng/mL)(P=0.003),primary histological type(other than well/moderately differentiated)(P=0.04),and primary lymph node metastases(≥1)(P=0.04)were identified as independent poor prognostic factors for overall survival(OS)in the upfront hepatectomy group.High-risk status was defined as the presence of two or more risk factors.After propensity score matching,50 patients were matched in each group.Among high-risk patients,the 5-year OS rate was significantly higher in the NAC group(13 patients)than in the upfront hepatectomy group(18 patients)(100%vs 34%;P=0.02).CONCLUSION NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.

关键词： Colorectal neoplasms Neoadjuvant therapy Neoplasm metastasis Prognosis Risk factors Survival

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IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

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World Journal of Gastroenterology 2014年第29期20卷 10050-10061页

作者： takafumi Naito Katsuhiko Nosho Miki Ito Hisayoshi Igarashi Kei Mitsuhashi Shinji Yoshii Hironori Aoki Masafumi Nomura Yasutaka Sukawa Eiichiro Yamamoto Yasushi Adachi Hiroaki Takahashi Masao Hosokawa Masahiro Fujita Toshinao Takenouchi Reo Maruyama Hiromu Suzuki Yoshifumi Baba Kohzoh Imai Hiroyuki Yamamoto Shuji Ogino Yasuhisa Shinomura Department of Gastroenterology Rheumatology and Clinical ImmunologySapporo Medical University School of Medicine Department of Gastroenterology Keiyukai Sapporo Hospital Center for Gastroenterology Teine-Keijinkai Hospital Department of Medical Oncolo-gy Dana-Farber Cancer InstituteBostonMA 02115United States Department of Surgery Keiyukai SapporoHospital Department of Pathology Keiyukai Sapporo Hospital Department of Molecular Biology Sapporo Medical University School of Medicine Department of Gastroenterological Surgery Graduate School of Medical ScienceKumamoto University Division of Cancer Research The Institute of Medical ScienceThe University of Tokyo Division of Gastroenterology and Hepatology Department of Internal MedicineSt.Marianna University School of Medicine

AIM:To investigate insulin-like growth factor 2(IGF2)differentially methylated region(DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions.METHODS:To accurately analyze the association between the histological types and molecular features of each type of serrated lesion,we consecutively collected1386 formalin-fixed paraffin-embedded tissue specimens that comprised all histological types[hyperplastic polyps(HPs,n=121),sessile serrated adenomas(SSAs,n=132),traditional serrated adenomas(TSAs,n=111),non-serrated adenomas(n=195),and colorectal cancers(n=827)].We evaluated the methylation levels of IGF2 DMR0 and long interspersed nucleotide element-1(LINE-1)in HPs(n=115),SSAs(n=120),SSAs with cytological dysplasia(n=10),TSAs(n=91),TSAs with high-grade dysplasia(HGD)(n=15),non-serrated adenomas(n=80),non-serrated adenomas with HGD(n=105),and CRCs(n=794).For the accurate quantification of the relative methylation levels(scale 0%-100%)of IGF2 DMR0 and LINE-1,we used bisulfite pyrosequencing method.Tumor specimens were analyzed for microsatellite instability,KRAS(codons 12 and 13),BRAF(V600E),and PIK3CA(exons 9and 20)mutations;MLH1 and MGMT methylation;and IGF2 expression by immunohistochemistry.RESULTS:The distribution of the IGF2 DMR0 methylation level in 351 serrated lesions and 185 non-serrated adenomas(with or without HGD)was as follows:mean61.7,median 62.5,SD 18.0,range 5.0-99.0,interquartile range 49.5-74.4.The IGF2 DMR0 methylation level was divided into quartiles(Q1≥74.5,Q2 62.6-74.4,Q3 49.6-62.5,Q4≤49.5)for further analysis.With regard to the histological type,the IGF2 DMR0 methylation levels of SSAs(mean±SD,73.1±12.3)were significantly higher than those of HPs(61.9±20.5),TSAs(61.6±19.6),and non-serrated adenomas(59.0±15.8)(P<0.0001).The IGF2 DMR0 methylation level was inversely correlated with the IGF2 expression level(r=-0.21,P=0.0051).IGF2 DMR0 hypomethylation was less frequently detected in SSAs compared with HPs,TSAs,and non-serrated adenomas(P<0.0001

关键词： BRAF Colon polyp Colorectal neoplasia Colorectum G

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