Duck-Woo Kim

Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial

BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated. The aim of the randomised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy. METHODS Between April 4, 2006, and Aug 26, 2009, patients with cT3N0-2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals. Patients were randomised 1:1 to receive either open surgery (n=170) or laparoscopic surgery (n=170), stratified according to sex and preoperative chemotherapy regimen. Short-term outcomes assessed were involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, recovery of bowel function, perioperative morbidity, postoperative pain, and quality of life. Analyses were based on the intention-to-treat population. Patients continue to be followed up for the primary outcome (3-year disease-free survival). This study is registered with ClinicalTrials.gov, number NCT00470951. FINDINGS Two patients (1.2%) in the laparoscopic group were converted to open surgery, but were included in the laparoscopic group for analyses. Estimated blood loss was less in the laparoscopic group than in the open group (median 217.5 mL [150.0-400.0] in the open group vs 200.0 mL [100.0-300.0] in the laparoscopic group, p=0.006), although surgery time was longer in the laparoscopic group (mean 244.9 min [SD 75.4] vs 197.0 min [62.9], p<0.0001). Involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, and perioperative morbidity did not differ between the two groups. The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group (time to pass first flatus, median 38.5 h [23.0-53.0] vs 60.0 h [43.0-73.0], p<0.0001; time to resume a normal diet, 85.0 h [66.0-95.0] vs 93.0 h [86.0-121.0], p<0.0001; time to first defecation, 96.5 h [70.0-125.0] vs 123 h [94.0-156.0], p<0.0001). The total amount of morphine used was less in the laparoscopic group than in the open group (median 107.2 mg [80.0-150.0] vs 156.9 mg [117.0-185.2], p<0.0001). 3 months after proctectomy or ileostomy takedown, the laparoscopic group showed better physical functioning score than the open group (0.501 [n=122] vs -4.970 [n=128], p=0.0073), less fatigue (-5.659 [n=122] vs 0.098 [n=129], p=0.0206), and fewer micturition (-2.583 [n=122] vs 4.725 [n=129], p=0.0002), gastrointestinal (-0.400 [n=122] vs 4.331 [n=129], p=0.0102), and defecation problems (0.535 [n=103] vs 5.327 [n=99], p=0.0184) in repeated measures analysis of covariance, adjusted for baseline values. INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery; the quality of oncological resection was equivalent.

Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes of an open-label, non-inferiority, randomised controlled trial

BACKGROUND Compared with open resection, laparoscopic resection of rectal cancers is associated with improved short-term outcomes, but high-level evidence showing similar long-term outcomes is scarce. We aimed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer. METHODS The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 18-80 years) with cT3N0-2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either open or laparoscopic surgery. Randomisation was stratified by sex and preoperative chemotherapy regimen. Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00470951. FINDINGS We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170). 3 year disease-free survival was 72·5% (95% CI 65·0-78·6) for the open surgery group and 79·2% (72·3-84·6) for the laparoscopic surgery group, with a difference that was lower than the prespecified non-inferiority margin (-6·7%, 95% CI -15·8 to 2·4; p<0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related. INTERPRETATION Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use. FUNDING National Cancer Center, South Korea.

Formation of Co nanoclusters in epitaxial Ti0.96Co0.04O2 thin films and their ferromagnetism

Anatase Ti0.96Co0.04O2 films were grown epitaxially on SrTiO3 (001) substrates by using pulsed laser deposition with in-situ reflection high-energy electron diffraction. The oxygen partial pressure, PO2, during the growth was systematically varied. As PO2 decreased, the growth behavior was changed from a two-dimensional layer-by-layer-like growth to a three-dimensional island-like one, which resulted in an increase in the saturation magnetization. These structural and magnetic changes were explained in terms of the formation of cobalt clusters whose existence was proved by transmission-electron-microscope studies. Our work clearly indicates that the cobalt clustering will cause room-temperature ferromagnetism in the Co-doped TiO2 films.

Low-Dose Abdominal CT for Evaluating Suspected Appendicitis

BACKGROUND Computed tomography (CT) has become the predominant test for diagnosing acute appendicitis in adults. In children and young adults, exposure to CT radiation is of particular concern. We evaluated the rate of negative (unnecessary) appendectomy after low-dose versus standard-dose abdominal CT in young adults with suspected appendicitis. METHODS In this single-institution, single-blind, noninferiority trial, we randomly assigned 891 patients with suspected appendicitis to either low-dose CT (444 patients) or standard-dose CT (447 patients). The median radiation dose in terms of dose-length product was 116 mGy·cm in the low-dose group and 521 mGy·cm in the standard-dose group. The primary end point was the percentage of negative appendectomies among all nonincidental appendectomies, with a noninferiority margin of 5.5 percentage points. Secondary end points included the appendiceal perforation rate and the proportion of patients with suspected appendicitis who required additional imaging. RESULTS The negative appendectomy rate was 3.5% (6 of 172 patients) in the low-dose CT group and 3.2% (6 of 186 patients) in the standard-dose CT group (difference, 0.3 percentage points; 95% confidence interval, -3.8 to 4.6). The two groups did not differ significantly in terms of the appendiceal perforation rate (26.5% with low-dose CT and 23.3% with standard-dose CT, P=0.46) or the proportion of patients who needed additional imaging tests (3.2% and 1.6%, respectively; P=0.09). CONCLUSIONS Low-dose CT was noninferior to standard-dose CT with respect to negative appendectomy rates in young adults with suspected appendicitis. (Funded by GE Healthcare Medical Diagnostics and others; ClinicalTrials.gov number, NCT00913380.).

Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer

BackgroundWe evaluated the association between a KRAS mutational status and various clinicopathologic features including the metastatic pattern in patients with metastatic or recurrent colorectal cancer (MRCRC). The concordance rates of the KRAS status between primary tumor sites and paired metastatic organs were also analyzed.MethodsThe KRAS mutational status in codons 12, 13, and 61 from formalin-fixed sections of both primary tumors and related metastases was determined by sequencing analysis. One hundred forty-three Korean patients with MRCRC with available tissues (resection or biopsy) from both primary tumors and related metastatic sites were consecutively enrolled.ResultsThe KRAS mutation rate was 52.4% (75/143) when considering both the primary and metastatic sites. When the relationship between the KRAS status and initial metastatic sites at the time of diagnosis of MRCRC was analyzed, lung metastasis was more frequent as the initial metastatic site in patients with the KRAS mutation than in patients without the KRAS mutation (45.3% vs. 22.1%; P = 0.003). However, liver (37.3% vs. 70.6%; P < 0.001) or distant lymph node metastases (6.7% vs. 19.1%; P = 0.025) were less frequent as the initial metastatic organ in patients with the KRAS mutation than in patients without the KRAS mutation. The discordance rate of KRAS mutational status between primary and paired metastatic sites other than the lung was 12.3% (13/106). Compared with primary tumor sites, the KRAS discordance rate was significantly higher in matched lung metastases [32.4% (12/37)] than in other matched metastatic organs (P = 0.005).ConclusionsOrgans initially involved by distant metastasis were different according to the KRAS mutational status in MRCRC patients. The concordance rate (87.7%) of the KRAS mutation status at metastatic sites other than the lung was generally high compared with primary tumor sites; however, lung metastasis had a high rate of KRAS discordance (32.4%).

Comparison of Early Mobilization and Diet Rehabilitation Program With Conventional Care After Laparoscopic Colon Surgery: A Prospective Randomized Controlled Trial

PURPOSE: Although laparoscopic surgery may permit earlier recovery compared with open surgery, no published randomized controlled trial has investigated the benefit of a multimodal rehabilitation program after laparoscopic colonic resection. This study aimed to evaluate the efficacy of a rehabilitation program after laparoscopic colon surgery in the context of a randomized controlled trial. METHODS: Between September 2007 and October 2009, 100 patients who had received laparoscopic colon surgery were selected for the study and randomly assigned on a 1:1 basis to a rehabilitation program group with early mobilization and diet (n = 46) or conventional care group (n = 54). The rehabilitation program group received early oral feeding, early ambulation, and regular laxative. The primary outcome was recovery time, measured with criteria of tolerable diet for 24 hours, safe ambulation, analgesic-free, and afebrile status without major complications. Secondary outcomes were postoperative hospital stay, complications, quality of life by Short Form 36, pain by visual analog scale, and readmission. This study was registered (ID number NCT00606944, http://register.clinicaltrials.gov). RESULTS: Recovery time was shorter in the rehabilitation program group than in the conventional care group (median (interquartile range), 4 (3–5) d vs 6 (5–7) d, respectively; P < .0001). There was no difference in postoperative hospital stay between the 2 groups (rehabilitation program group, 7 (6–8) d vs conventional care group, 8 (7–9) d; P = .065). There was no difference in complication rates between the rehabilitation program group and conventional care group (10.9% vs 20.4%, respectively; P = .136). Quality of life and pain were similar in both groups. There were no readmissions or mortality. CONCLUSIONS: A rehabilitation program with early mobilization and diet after laparoscopic colon surgery results in reduced recovery time without increased complications. These results suggest that a multimodal rehabilitation program may increase the short-term benefits after laparoscopic colon surgery.

Quantitative determination of mycotoxins in urine by LC-MS/MS.

Naturally occurring mycotoxins are responsible for a wide array of adverse health effects. The measurement of urinary mycotoxin levels is a useful means of assessing an individuals exposure, but the development of sensitive and accurate analytical methods for detecting mycotoxins and their metabolites in urine samples is challenging. Urinary mycotoxins are present in low pg ml–1 concentrations, and the chromatographic identification of their metabolites can be obscured by other endogenous metabolites. We developed an analytical method focused on the selection of two appropriate multiple-reaction monitoring transition for unambiguous identification and quantification of carcinogenic aflatoxin M1 (AFM1), ochratoxin A (OTA) and fumonisin B1, B2 (FB1, FB2) in urine samples from a small volunteer group in a pilot study. AFM1, OTA, FB1 and FB2 were concentrated selectively, interfering substances were removed using an immunoaffinity column (IAC), and mycotoxins were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in combination with a stable-isotope standard-dilution assay (SIDA). The method was sensitive enough to measure mycotoxins and their metabolites at pg ml–1 levels in urine. The combination of LC-MS/MS and SIDA was critical to distinguishing pseudo-OTα interference from genuine OTα. Twelve urine samples contained OTA ranging from 0.013 to 0.093 ng ml−1 (mean = 0.031 ng ml−1). AFM1 were detected in one sample at a 0.002 ng ml−1 level, while FB1 and FB2 were undetectable in all 12 samples. None of the samples in this pilot study contained a detectable level of OTα, despite the presence of OTA, and this may suggest the need for further epidemiological investigation of OTA exposure in the Korean population.

The role of carcinoembryonic antigen after neoadjuvant chemoradiotherapy in patients with rectal cancer.

PURPOSE: The purpose of this study was to evaluate the role of CEA after neoadjuvant chemoradiotherapy in patients with rectal cancer. METHODS: This study involved 109 patients with rectal cancer who were treated with preoperative chemoradiotherapy and curative resection. Preoperative serum CEA levels were measured twice, before chemoradiotherapy administration and 4 weeks after chemoradiotherapy. Surgery was performed 6 to 9 weeks after neoadjuvant chemoradiotherapy. RESULTS: The 3-year disease-free survival rate was 85.0%. On univariate analysis, prechemoradiotherapy CEA level, postchemoradiotherapy CEA level, tumor regression grade, ypT, ypN, circumferential resection margin, lymphatic invasion, venous invasion, and perineural invasion were associated with disease-free survival. Based on univariate analysis (group 1: prechemoradiotherapy CEA ≤3.5; group 2: prechemoradiotherapy CEA >3.5, postchemoradiotherapy CEA ≤2.7; group 3: prechemoradiotherapy CEA >3.5, postchemoradiotherapy CEA >2.7), we categorized patients into 3 groups according to their pre- and postchemoradiotherapy CEA levels (ng/mL). The 3-year disease-free survival rate was significantly better in groups 1 and 2 (94.7% and 88.0%) than in group 3 (52.6%, P < .001). On multivariate analysis, tumor regression grade (P = .036), ypN (P = .036), and CEA groups (P = .022) were identified as independent prognostic factors for disease-free survival. Furthermore, postchemoradiotherapy CEA ≤2.7 ng/mL was an independent predictor of good tumor regression (P = .001), ypT0 to 2 (P = .002), and ypN0 (P = .001). CONCLUSIONS: Combined pre- and postchemoradiotherapy CEA levels could be useful as a prognostic factor for disease-free survival in patients with rectal cancer who undergo treatment with neoadjuvant chemoradiotherapy and curative resection. Postchemoradiotherapy CEA may be helpful in a selection of patients who want more conservative surgery after chemoradiotherapy.

Dynamics of mode competition in a gigawatt-class magnetically insulated line oscillator

An axial mode competition is observed in a 1GHz magnetically insulated line oscillator operating at gigawatt power level with a pulse duration of 130ns. A fast-growing axial mode adjacent to desired π-mode starts up first and hops to the slow-growing and stable π mode. The dynamics of the mode competition is found to be strongly dependent on the time-varying axial velocity of the magnetically insulated electron beam. The experimental observation is verified by the particle-in-cell simulation using a time-frequency analysis.

Influence of a bimodal eutectic structure on the plasticity of a (Ti70.5Fe29.5)91Sn9 ultrafine composite

Systematic investigations on the microstructural evolution of a bimodal eutectic (Ti70.5Fe29.5)91Sn9 ultrafine composite containing Ti3Sn dendrites upon compression reveal that local deformation of the dendrites dominates the early stage of deformation with a plastic strain of ep=5.8%. After further deformation (ep=10.2%), a wavy propagation of shear bands indicative of dissipation of the shear stress is caused by a rotation of the coarse eutectic structure along the interfaces of the bimodal eutectic structure.