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Phase II Trial of Neoadjuvant Chemotherapy, Chemoradiotherapy, and Laparoscopic Surgery with Selective Lateral Node Dissection for Poor-Risk Low Rectal Cancer.
Konishi, T, Shinozaki, E, Murofushi, K, Taguchi, S, Fukunaga, Y, Nagayama, S, Fujimoto, Y, Akiyoshi, T, Nagasaki, T, Suenaga, M, et al
Annals of surgical oncology. 2019;(8):2507-2513
Abstract
PURPOSE The aim of this study is to evaluate the safety and efficacy of induction modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab followed by S- 1-based chemoradiotherapy in magnetic resonance imaging (MRI)-defined poor-risk locally advanced low rectal cancer. PATIENTS AND METHODS This was a prospective phase II trial at a single comprehensive cancer center. The primary endpoint was the pathological complete response (pCR) rate. Eligible patients had clinical stage II-III low rectal adenocarcinoma with any of the following MRI-defined poor-risk features: circumferential resection margin (CRM) ≤ 1 mm, cT4, positive lateral nodes, mesorectal N2 disease, and/or requiring abdominoperineal resection. Patients received six cycles of mFOLFOX6 with 5 mg/kg bevacizumab followed by oral S-1 (80 mg/m2/day on days 1-14 and 22-35) plus radiotherapy (50.4 Gy). Surgery was conducted through a laparoscopic approach. Lateral node dissection was selectively added when the patient had enlarged lateral nodes. RESULTS A total of 43 patients were enrolled. Grade 3-4 adverse events occurred in nine patients during induction chemotherapy and in five patients during chemoradiotherapy. One patient declined surgery with a clinical complete response. Forty-two patients underwent surgery, and 16 had pCR [37.2%, 95% confidence interval (CI) 24.4-52.1%]. All underwent R0 resection without conversion, including combined resection of adjacent structures (n = 14) and lateral node dissection (n = 30). Clavien-Dindo grade 3-4 complications occurred in six patients (14.3%). With median follow-up of 52 months, six developed recurrences (lung n = 5, local n = 1; 3-year relapse-free survival 86.0%). CONCLUSIONS This study achieved a high pCR rate with favorable toxicity and postoperative complications in poor-risk locally advanced low rectal cancer. Multicenter study is warranted to evaluate this regimen.
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Comparison of postoperative lymphocytes and interleukins between laparoscopy-assisted and open radical gastrectomy for early gastric cancer.
Xia, X, Zhang, Z, Xu, J, Zhao, G, Yu, F
The Journal of international medical research. 2019;(1):303-310
Abstract
OBJECTIVE This study aimed to study the effects of laparoscopic-assisted radical gastrectomy (LAG) and open radical gastrectomy (OG) on immune function and inflammatory factors in patients with early gastric cancer. METHODS Seventy-five patients with pT1N0M0 gastric cancer in Ren Ji Hospital from August 2017 to January 2018 were studied. Lymphocytes subsets and interleukins were compared preoperatively and on the third postoperative day (POD3) and seventh postoperative day (POD7). RESULTS There were no significant differences in age, sex, body mass index, duration of the operation, estimated blood loss, total gastrectomy rate, postoperative first fluid diet, and the levels of preoperative lymphocytes subsets and interleukins between the two groups. The number of CD4+ T cells and the CD4+/CD8+ ratio in the LAG group were significantly higher than those in the OG group on POD3. However, the number of CD8+ T cells, and interleukin-6 and interleukin-8 levels in the LAG group were significantly lower than those in the OG group on POD3. CONCLUSIONS Laparoscopy can effectively reduce the levels of inflammatory factors and has less effect on the immune system than OG.
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Laparoscopic Roux-en-Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates.
Puris, E, Pasanen, M, Ranta, VP, Gynther, M, Petsalo, A, Käkelä, P, Männistö, V, Pihlajamäki, J
Basic & clinical pharmacology & toxicology. 2019;(2):123-132
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Abstract
There is a lack of information about the changes in drug pharmacokinetics and cytochrome P450 (CYP) metabolism after bariatric surgery. Here, we investigated the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery on pharmacokinetics of nine drugs given simultaneously which may reveal changes in the activities of the main CYPs. Eight obese subjects undergoing LRYGB received an oral cocktail containing nine drugs, substrates of various CYPs: melatonin (CYP1A2), nicotine (CYP2A6), bupropion (CYP2B6), repaglinide (CYP2C8), losartan (CYP2C9), omeprazole (CYP2C19/CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A). The 6-hours pharmacokinetic profiles in serum and urine of each drug or corresponding metabolite as well as their metabolic ratios were compared before surgery with those at a median 1 year later. LRYGB exerted variable effects on the pharmacokinetics of these drugs. The geometric mean AUC0-6 (90% confidence interval) of melatonin, bupropion, repaglinide, chlorzoxazone and midazolam after LRYGB was 27 (19%-41%), 54 (43%-67%), 44 (29%-66%), 160 (129%-197%) and 74 (62%-90%) of the pre-surgery values, respectively. The pharmacokinetics of losartan, omeprazole and dextromethorphan did not change in response to surgery. Nicotine was not detected in serum, while geometric mean of AUC0-6 of its metabolite, cotinine, increased by 1.7 times after surgery. There were 3.6- and 1.3-fold increases in the AUC ratios of 6-hydroxymelatonin/melatonin and hydroxybupropion/bupropion, respectively. The cocktail revealed multiple pharmacokinetic changes occurring after LRYGB with the greatest effects observed for CYP1A2, CYP2C8 and CYP2E1 substrates. Future studies should be focused on CYP1A2, CYP2A6, CYP2C8 and CYP2B6 to clarify the changes in activities of these enzymes after LRYGB.