Publications by authors named "Masashi Tsuruta"

52 Publications

Colectomy risk score predicts pouchitis in patients with ulcerative colitis.

Updates Surg 2021 Sep 7. Epub 2021 Sep 7.

Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan.

Risk stratification is required to improve the management of pouchitis with ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA). Recently, the colectomy risk score (CRS) has been used to assess UC severity and predict the need for surgery. We explored whether the CRS predicted pouchitis in patients with UC who underwent IPAA. This retrospective study included 168 UC patients who underwent IPAA. Pouchitis was diagnosed according to the pouchitis disease activity index. The primary endpoint was the cumulative incidence of pouchitis. The risk factors for pouchitis using preoperatively obtained data, including the CRS, were investigated. Based on their CRS, patients were assigned to low- (scores 0-3), intermediate- (scores 4-6), and high-risk (scores 7-9) groups. The incidence of pouchitis was estimated using the Kaplan-Meier curve. CRS validity was assessed using the Cox proportional hazards model. During the median 7.2 (interquartile range [IQR] 2.8-11.1) years' follow-up, 37 (28.5%) patients were diagnosed with pouchitis. Patients with pouchitis had significantly higher CRS than patients without pouchitis (median 7.0; IQR, 4.0-7.0 vs median 5.0; IQR, 3.0-7.0). The cumulative incidences of pouchitis in the low-, intermediate-, and high-risk groups were 10.3%, 18.3%, and 36.1% at 5 years, respectively. Thus, the incidence trended to increase significantly as CRS increased. Multivariate analysis revealed high-risk CRS status was an independent predictor of pouchitis (hazard ratio: 18.03; 95% confidence interval 1.55-210.05). CRS is useful in risk stratification for the development of subsequent pouchitis in patients with UC undergoing IPAA.
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http://dx.doi.org/10.1007/s13304-021-01166-5DOI Listing
September 2021

Surgical glove perforation during laparoscopic colorectal procedures.

Surg Endosc 2021 Aug 11. Epub 2021 Aug 11.

Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Background: It has been reported that in conventional open surgery, approximately 10% of surgical gloves are perforated during surgery without being noticed. To protect both the patient and medical staff from harm, double gloving or changing gloves routinely at certain intervals during surgery is recommended. However, whether these protective measures are also necessary for laparoscopic colorectal surgery is unknown because the actual perforation rate during laparoscopic procedures is unclear.

Methods: Seventy-seven laparoscopic colorectal surgeries were evaluated, and a total of 616 surgical gloves used in the surgeries were collected for analysis. The presence of glove perforation was tested by the standard water-leak test method (EN455-1).

Results: Seven perforations were detected (1.1%). The duration of the laparoscopic procedure was not a statistically significant risk factor for glove perforation (p = 0.41). Postoperative surgical site infections (SSIs) were observed in 12 cases (15.6%), but there was no significant correlation between the presence of glove perforation and SSI (p = 0.92). According to the bacterial cultivation results, the majority of causative agents of SSI were enterobacteria, which belong to the major gut flora.

Conclusion: Although the perforation rate was considerably lower than that in open surgery, surgical glove perforation occurred during laparoscopic procedures. Double gloving in laparoscopic colorectal surgery is recommended not to prevent SSI but to protect medical workers from harmful infections after direct contact with the patient.
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http://dx.doi.org/10.1007/s00464-021-08670-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356683PMC
August 2021

Impact of intraoperative hypocapnia on postoperative complications in laparoscopic surgery for colorectal cancer.

Surg Today 2021 Jun 29. Epub 2021 Jun 29.

Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Purpose: In laparoscopic surgery (LS) for colorectal cancer (CRC), the relationship between intraoperative end-tidal carbon dioxide concentration (EtCO) and surgery-related complications remains unexplored. This study assessed the impact of intraoperative EtCO on postoperative complications in LS for CRC.

Methods: In total, 909 patients who underwent LS for CRC were enrolled. Hypocapnia and hypercapnia were defined as EtCO < 35 mmHg and > 40 mmHg, respectively, and the relationships between hypocapnia or hypercapnia duration and postoperative complications were analyzed.

Results: The median (range) durations of hypocapnia and hypercapnia were 2.0 (0-8.3) h and 0.3 (0-5.8) h, respectively. Complications were observed in 208 cases (23.0%), which included 37 (4.1%) instances of anastomotic leakage and 86 (9.5%) of superficial surgical site infection (SSI). While the hypercapnia duration was not associated with the short-term outcomes, prolonged hypocapnia was significantly correlated with complications (p = 0.02), specifically superficial SSI (p = 0.005). Multivariate analyses adjusted for confounding factors confirmed that hypocapnia prolongation was an independent risk factor for postoperative superficial SSI [OR 1.19; 95% confidence interval (Cl) 1.03-1.36, p = 0.01].

Conclusion: Intraoperative hypocapnia may be a risk factor for postoperative complications, in particular superficial SSI, in LS for CRC.
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http://dx.doi.org/10.1007/s00595-021-02315-4DOI Listing
June 2021

Lymph node metastasis is strongly associated with lung metastasis as the first recurrence site in colorectal cancer.

Surgery 2021 Sep 24;170(3):696-702. Epub 2021 Apr 24.

Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.

Background: The lymphatic system is known to be the primary pathway of metastasis for colorectal cancer. However, beyond regional lymph node metastases, little is known about the pathway of lymphatic metastases and the differences in the recurrence site risk. The aim of this study was to clarify the relationship between lymph node metastasis and the first recurrence site in colorectal cancer.

Methods: Patients with colorectal cancer who underwent curative resection in our institution between January 2003 and December 2016 were included in this analysis. The relationship between the first recurrence site and clinicopathological factors was analyzed by the Cox regression model and competing risk regression model.

Results: In total, 1,249 patients with colorectal cancer were included in this analysis. We found that the stages of lymph node metastases (N0 vs N1: P = .008, N0 vs N2a: P < .001, N0 vs N2b: P < .001) were significantly associated with lung metastasis in the multivariate analysis. Furthermore, in the competing risk analysis, the stages of lymph node metastases were significantly correlated with lung metastasis (N0 vs N1: P = .002, N0 vs N2a: P < .001, N0 vs N2b: P < .001) but were not correlated with other recurrence sites.

Conclusion: The severity of lymph node involvement had a strong correlation with lung metastases in patients with colorectal cancer.
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http://dx.doi.org/10.1016/j.surg.2021.03.017DOI Listing
September 2021

Inhibition of Heat-shock Protein 27 Reduces 5-Fluorouracil-acquired Resistance in Human Colon Cancer Cells.

Anticancer Res 2021 Mar;41(3):1283-1290

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Background/aim: In previous work we showed that expression of heat-shock protein 27 (HSP27; encoded by HSPB1) was associated with inherent resistance to 5-fluorouracil (5-FU). However, the relationship between HSP27 and acquired resistance remains unknown.

Materials And Methods: We generated an acquired resistance model (WiDr-R) of a colon cancer cell line by exposing WiDr cells to 5-FU. Cell viability assays under treatment with 5-FU, as well as down-regulation of HSP27 using small interfering HSP27 RNA, were performed. HSP27 mRNA and protein expression was analyzed using real-time polymerase chain reaction and western blotting.

Results: 5-FU-acquired resistance induced overexpression of HSP27 mRNA and protein levels in WiDr-R cells. Furthermore, siRNA knockdown of HSP27 in WiDr-R cells reduced 5-FU-acquired resistance.

Conclusion: These findings demonstrate that HSP27 is associated with 5-FU resistance in human colon cancer cell cells and suggest that HSP27 regulation represents a novel approach to overcoming chemoresistance in colorectal cancer.
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http://dx.doi.org/10.21873/anticanres.14885DOI Listing
March 2021

Horizontal spread of pericolic lymph node metastasis as a prognostic factor for recurrence in Stage III colorectal cancer.

Colorectal Dis 2021 06 1;23(6):1370-1378. Epub 2021 Mar 1.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Aim: Main lymph node (LN) metastasis dissected with a high vascular tie at the root of the feeding artery is a poor prognostic factor in colorectal cancer (CRC). However, the effects of horizontal spread on recurrence after curative resection remain unclear. The purpose of this study is to evaluate the relationship between the horizontal spread of LN metastasis and recurrence in CRC.

Method: In this retrospective study, 189 CRC patients (98 men, 91 women) who underwent curative resection at our hospital from 2003 to 2018 and had only pericolic LN metastasis were divided into two groups: patients with LN metastasis beside the tumour only (T group, n = 121) and those with LN metastasis with horizontal spread (S group, n = 68) (mean follow-up period 50.9 ± 34.1 months). The primary outcome was recurrence-free survival (RFS). We investigated the correlation between clinicopathological background factors and recurrence using Cox regression analysis.

Results: Fewer than three LN metastases (N1) were found in 157 patients (107 T group, 50 S group), and four or more metastases (N2a) were found in 32 patients (14 T group, 18 S group). Univariate analyses revealed significantly shorter RFS in the S group [hazard ratio (HR) 1.95, 95% CI 1.07-3.55; p = 0.03). Multivariate analyses revealed that horizontal spread is an independent risk factor for recurrence (HR 1.95, 95% CI 1.05-3.68; p = 0.03).

Conclusion: Although further investigation is needed, horizontal spread of LN metastasis is a prognostic factor for recurrence in Stage III CRC.
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http://dx.doi.org/10.1111/codi.15586DOI Listing
June 2021

Association of surfactant protein D with pulmonary metastases from colon cancer.

Oncol Lett 2020 Dec 5;20(6):322. Epub 2020 Oct 5.

Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.

Surfactant protein D (SP-D) is a member of the collectin family of proteins, which is secreted by airway epithelial cells. SP-D serves an important role in the immune system and in the inflammatory regulation of the lung. SP-D was recently found to suppress lung cancer progression by downregulating epidermal growth factor signaling. However, the relationship between SP-D and pulmonary metastases from colon cancer remains unknown. The present study aimed to determine whether SP-D may suppress the development of the mouse rectal carcinoma cell line, CMT93, . The present study investigated the effect of SP-D on pulmonary metastases from colon cancer using SP-D knockout mice. A wound healing assay and cell invasion assay revealed that SP-D suppressed the proliferation, migration and invasion of CMT-93 cells. After injection of CMT-93 cells into the tail vein, SP-D knockout mice were significantly more susceptible to developing pulmonary metastases than C57/BL6 mice (control). Moreover, a novel cell line (CMT-93 pulmonary metastasis; CMT-93 PM) was established from the lesions of pulmonary metastases in C57/BL6 mice following injection of CMT93 into the tail vein. CMT-93 PM exhibited more robust invasion and proliferation compared to CMT93, which was unaffected by exposure to SP-D. A higher incidence of pulmonary metastases was detected following injection of CMT93 PM into the tail vein of C57/BL6 mice compared with CMT-93. Consequently, SP-D may be involved in the pathogenesis of pulmonary metastases from colon cancer.
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http://dx.doi.org/10.3892/ol.2020.12185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583848PMC
December 2020

The Impact of Smoking on Pulmonary Metastasis in Colorectal Cancer.

Onco Targets Ther 2020 30;13:9623-9629. Epub 2020 Sep 30.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Introduction: Recently, clinical studies have revealed that smoking can contribute to the poor prognosis of colorectal cancer (CRC) and, additionally, can be a risk factor for pulmonary metastasis of CRC. However, there has been no basic research regarding the underlying molecular mechanism. The purpose of this study was to clarify the mechanism by which smoking causes pulmonary metastasis of CRC.

Methods: First, pulmonary metastasis model mice inhaled cigarette smoke or air (control) for 1 h once a day for 3 weeks. We attempted to clarify the effect of smoking on the incidence of pulmonary metastasis. On the 15th day, CMT-93 cells were injected into the tail vein. At 6 and 8 weeks following injection, the extent of pulmonary metastasis was evaluated using in vivo micro CT. After the last CT examination, the mice were sacrificed, and the lungs were extracted for pathological examination.

Results: The number of mice with pulmonary metastases in the smoking group was significantly higher than in the control group. Three weeks of smoking induced mild inflammation in the lungs, as evidenced by increases in the levels of IL-6 and TNF-α in bronchoalveolar lavage. Moreover, the adhesion-related molecule ICAM-1 was overexpressed in pulmonary tissue, which allowed drained cancer cells to remain in the lung and contribute to the formation of pulmonary metastasis.

Conclusion: Collectively, cigarette smoking may contribute to the pathogenesis and development of pulmonary metastasis in CRC through enhancement of adhesion and inflammation.
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http://dx.doi.org/10.2147/OTT.S263250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533240PMC
September 2020

The Utility of the Colectomy Risk Score in Terms of Predicting Postoperative Complications in Patients with Ulcerative Colitis.

J Gastrointest Surg 2021 02 11;25(2):526-529. Epub 2020 Sep 11.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1007/s11605-020-04756-7DOI Listing
February 2021

External radiofrequency as a novel extracorporeal therapy for emphysema.

Eur Respir J 2020 11 12;56(5). Epub 2020 Nov 12.

Centre for Heart Lung Innovation, St Paul's Hospital, and Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada

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http://dx.doi.org/10.1183/13993003.01422-2020DOI Listing
November 2020

Relationship between anastomotic leakage and CT value of the mesorectum in laparoscopic anterior resection for rectal cancer.

Jpn J Clin Oncol 2020 Apr;50(4):405-410

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Objective: This study aims to indicate whether the CT value of the mesorectum could be correlated with the incidence of anastomotic leakage (AL) in laparoscopic surgery for rectal cancer.

Methods: The study subjects included 173 patients who underwent laparoscopic anterior resection (LAR) for rectal cancer from September 2005 to 2016 in our institution as well as reliable contrast-enhanced CT preoperatively. Univariate and multivariate analyses were performed to determine the correlation between surgical outcomes, including AL and CT value of the mesorectum.

Results: AL was observed in 30 (17.3%) patients. Amongst short-term surgical outcomes, overall complication showed significant correlation with the CT value of the mesorectum (P = 0.003). In addition, AL was the only factor, which significantly correlated with the CT value of the mesorectum (P = 0.017). By plotting receiver operating characteristic curve, -75 HU was the threshold of the CT value of the mesorectum for predicting AL with an area under the curve of 0.772. Categorized into two groups as per the threshold, low group showed significantly higher incidence of AL (OR, 2.738; 95% CI, 1.105-6.788; P = 0.030) as well as whole complications (OR, 4.431; 95%CI, 1.912-10.266; P = 0.001).

Conclusion: The CT value of the mesorectum may be a helpful preoperative radiological biomarker to predict AL after LAR for rectal cancer.
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http://dx.doi.org/10.1093/jjco/hyz192DOI Listing
April 2020

Evolution of surgery for rectal cancer: Transanal total mesorectal excision~new standard or fad?~.

J Anus Rectum Colon 2018 29;2(4):115-121. Epub 2018 Oct 29.

University Hospitals NHS Trust, Derriford Hospitals NHS Trust, Plymouth, UK.

Transanal Total Mesorectal Excision (TaTME) has recently been developed to overcome the difficulties associated with conventional laparoscopic or robotic TME. TaTME has gained popularity and becomes the center of attention among colorectal surgeons globally. The present review aims to update the literature, clarify the current status and perspectives of TaTME. Complete TaTME specimens were obtained in 85-97.1% of the case; the reported circumferential resection margin (CRM) ranged from 1.5% to 8.1%, whereas and distal resection margin (DRM) positive rates ranged from 0% to 3.2%. The conversion rate of TaTME occurred from 0 to 15%, and there was no difference between TaTME and laparoscopic or robotic TME. Intraoperative complications occurred in 5-6% of the case, which compared favorably to laparoscopic TME. The most serious intraoperative complication with this approach was urethral injury, although only small numbers were reported, which was possibly due to under-reporting. Clavien-Dindo I or II postoperative complications occurred in 22-24% of the case, and III or IV in 10-11% of the case, which did not differ between TaTME and laparoscopic or robotic TME. TaTME may be technically easier and more beneficial than laparoscopic, robotic or open TME in male patients with a narrow pelvis; in obese patients with a bulky tumor. At present two randomized controlled trials, COLOR III and GRECCAR, and comparing TaTME with laparoscopic TME are being conducted and their outcomes are awaited. TaTME is a complex procedure, but proved to be feasible, oncologically safe, and effective in difficult cases. Before this new technique is adopted, proper training with Proctor/mentorship is strongly advised. Careful case selection and audit of data are mandatory.
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http://dx.doi.org/10.23922/jarc.2018-029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752134PMC
October 2018

Comparison of olanexidine versus povidone-iodine for preventing surgical site infection in gastrointestinal surgery: study protocol for a multicentre, single-blind, randomised controlled clinical trial.

BMJ Open 2019 05 28;9(5):e028269. Epub 2019 May 28.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Introduction: The prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries.

Methods And Analysis: We propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method.

Ethics And Dissemination: The protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals.

Trial Registration Number: UMIN 000031560; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2018-028269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549615PMC
May 2019

Interleukin-13 and its signaling pathway is associated with obesity-related colorectal tumorigenesis.

Cancer Sci 2019 Jul 18;110(7):2156-2165. Epub 2019 Jun 18.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6-week-old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK-Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)-13 and IL-13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL-13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL-13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti-inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL-13, could play an important role in the carcinogenesis of obesity-related CRC.
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http://dx.doi.org/10.1111/cas.14066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609806PMC
July 2019

The impact of the mesorectal apparent diffusion coefficient value on surgical difficulty in laparoscopic anterior resection for rectal cancer.

Surg Today 2019 Mar 19;49(3):239-244. Epub 2018 Oct 19.

Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan.

Purpose: We aimed to clarify the impact of the apparent diffusion coefficient (ADC) value of the mesorectum from preoperative magnetic resonance imaging (MRI) on surgical difficulty in laparoscopic anterior resection (Lap-AR) for rectal cancer.

Methods: In total, 67 patients who had undergone curative Lap-AR for rectal cancer in our hospital from January 2008 to March 2015 and had preoperative MRI findings available were included. We randomly calculated the average ADC in three regions of the mesorectum at the level of the upper edge of the superior border of the femur. Univariate and multivariate analyses were performed to evaluate the correlation between the patients' clinicopathological characteristics, including the ADC value and short-term surgical outcomes.

Results: The univariate analysis revealed that a lower ADC value was associated with a significantly increased operative blood loss (p = 0.008) and prolonged operative time (p < 0.001). The multivariate analysis adjusted for the body mass index, anal verge, tumor location, covering stoma, clinical T factor and conversion revealed that the ADC value was an independent risk factor for a prolonged operative time (R = 0.6003, p < 0.001). Furthermore, the multivariate analysis adjusted for the body mass index, anal verge, covering stoma, clinical T factor and conversion revealed that the ADC value was an independent risk factor for an increased blood loss (R = 0.4345, p = 0.008).

Conclusion: A lower ADC value of the mesorectum might be a predictor of surgical difficulty in Lap-AR for rectal cancer.
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http://dx.doi.org/10.1007/s00595-018-1727-7DOI Listing
March 2019

Adhesive intestinal obstruction increases the risk of intestinal perforation in peritoneal dialysis patients: a case report.

BMC Nephrol 2018 06 28;19(1):153. Epub 2018 Jun 28.

Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Background: Peritonitis secondary to bowel perforation is a rare and potentially fatal complication in peritoneal dialysis (PD) patients. However, the early diagnosis of bowel perforation is difficult in PD patients because the initial symptoms and signs of bowel perforation are similar to those of PD-associated peritonitis. Furthermore, the risk of bowel perforation in PD patients is unclear. Here, we present a case of intestinal perforation located at the site of adhesive intestinal obstruction in a PD patient.

Case Presentation: A 73-year-old man on PD presented with progressive worsening of abdominal pain and cloudy peritoneal fluid. The peritoneal fluid cell count was increased to 980/ml and peritoneal dialysis-associated peritonitis was diagnosed. Computed tomography showed local adhesions causing agglomeration of the dilated intestine. He initially responded to antibiotic treatment; however, his abdominal pain was rapidly worsened after resumption of oral intake. On hospital day 23, computed tomography showed loss of contents from the dilated intestine and discharge of fecal material from the PD tube was noted. Thus, small bowel perforation was diagnosed, and he underwent ileocecal resection with colostomy creation. As indicators of EPS was not evident, PD catheter was removed. Since then, he has been on maintenance of hemodialysis since then.

Conclusion: The findings of the present case suggest that adhesive intestinal obstruction in PD patients can increase the risk of intestinal perforation. Careful monitoring for the early detection of intestinal perforation is required in such cases.
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http://dx.doi.org/10.1186/s12882-018-0954-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022445PMC
June 2018

Needlescopic versus conventional laparoscopic surgery for colorectal cancer ~a comparative study~.

J Anus Rectum Colon 2017 25;1(2):45-49. Epub 2018 May 25.

Department of Surgery, Keio University School of Medicine.

Objectives: This study set out to determine whether Needlescopic surgery (NS) produces comparable surgical outcomes for patients with colorectal cancer (CRC) compared to conventional multi-port laparoscopic surgery (MPS).

Methods: We used the five-port method with a 3.5 cm umbilical incision for extraction and reconstruction during MPS for CRC. One or two 5 mm ports were exchanged for needle forceps and all surgical procedures were as for previous MPS since July 2012. We investigated the short-term outcomes of 138 consecutive patients who underwent curative resection of CRC by NS (July 2012-August 2014) and 130 consecutive patients with CRC treated with MPS during a previous period (January 2010-June 2012).

Results: Operative time in the NS group was comparable to that of MPS (p=0.467); the NS group had significantly less estimated blood loss (p=0.002) and a shorter postoperative hospital stay (p<0.001). The mean number of dissected lymph nodes was 27 in both groups (p=0.730). No mortality occurred in either group, and similar morbidity rates were observed (p=0.454).

Conclusions: NS using Endo Relief needle forceps is a safe and feasible option compared to conventional MPS for CRC.
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http://dx.doi.org/10.23922/jarc.2016-007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768669PMC
May 2018

Heat shock protein 27 knockdown using nucleotide‑based therapies enhances sensitivity to 5-FU chemotherapy in SW480 human colon cancer cells.

Oncol Rep 2018 Mar 3;39(3):1119-1124. Epub 2018 Jan 3.

Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.

Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer. In the present study, we examined the impact of Hsp27 downregulation (via apatorsen) on 5-FU sensitivity in colon cancer both in vitro and in vivo. In vitro, apatorsen significantly decreased the levels of Hsp27 in a dose-dependent manner in human colon cancer SW480 cells. A cell proliferation assay revealed that although apatorsen did not inhibit tumor growth, it resulted in greater 5-FU sensitivity in comparison with treatment with OGX-411 (control). In vivo, intraperitoneal injection of apatorsen decreased the levels of Hsp27 in subcutaneous tumors in a xenograft mouse model using SW480 cells and enhanced 5-FU sensitivity, compared to controls. Although further research is warranted, the present study confirmed that concurrent treatment with Hsp27 knockdown using apatorsen and 5-FU could be a promising therapy for colon cancer.
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http://dx.doi.org/10.3892/or.2018.6180DOI Listing
March 2018

Cetuximab promotes SN38 sensitivity via suppression of heat shock protein 27 in colorectal cancer cells with wild-type RAS.

Oncol Rep 2017 Aug 21;38(2):926-932. Epub 2017 Jun 21.

Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo 160-8582, Japan.

Combination treatment with cetuximab and CPT-11 produces beneficial and synergistic effects in wild-type RAS metastatic colorectal cancer (mCRC) patients. However, the mechanism underlying this synergism is not yet understood. We examined whether cetuximab had a synergistic effect with CPT-11 and its active metabolite, SN38, and examined the molecular mechanism of the synergism between cetuximab and SN38 in CRC cells with various mutational status. We hypothesized that cetuximab promotes sensitivity to SN38 via suppression of heat shock protein 27 (HSP27), a protein involved in multidrug resistance through blocking the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which is associated with chemosensitivity. Four human CRC cell lines with different RAS and BRAF mutational status were used. Expression levels of HSP27 protein correlated with SN38 sensitivity in these cell lines (R=0.841, p=0.159). Exposure to cetuximab and various concentration of AG490, an inhibitor of JAK2, STAT3 and HSP27 protein levels, except in the KRAS G12V mutant line, SW620. A synergistic effect of cetuximab in combination with SN38 was observed in RAS and BRAF wild-type cells (here, Caco2), but not in the three other RAS- or BRAF-mutated cell lines. These results indicate that cetuximab may promote sensitivity to SN38 via suppression of HSP27 through blocking the JAK/STAT pathway in Caco2 cells. The mutational status of numerous downstream effectors, such as RAS and BRAF, is important in mono- or combination therapy with cetuximab. In conclusion, cetuximab may promote SN38 sensitivity via suppression of HSP27, through blocking the JAK/STAT signaling pathway, and shows synergistic effects when combined with SN38 in wild-type RAS CRC cells.
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http://dx.doi.org/10.3892/or.2017.5734DOI Listing
August 2017

Pelvic inlet shape measured by three-dimensional pelvimetry is a predictor of the operative time in the anterior resection of rectal cancer.

Surg Today 2018 Jan 8;48(1):51-57. Epub 2017 Jun 8.

Department of Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjyuku-ku, Tokyo, 160-8582, Japan.

Purpose: We evaluated pelvic shape as a predictor of the surgical outcome of anterior resection in patients with rectal cancer.

Methods: In total, 228 patients who had undergone anterior resection (R0 resection and double-stapling anastomosis) for rectal cancer from 2005 to 2014 were included in this study. The anteroposterior (AP) and transverse (T) diameters of the pelvic inlet and outlet and pelvic depth were analyzed on three-dimensional volume-rendered images, and the AP/T ratio was calculated. Univariate and multivariate analyses were performed to determine the predictive significance of the operative time and intraoperative blood loss as surgical outcomes.

Results: No difference was observed between the inlet AP/T and patient sex ratios, but the other pelvic dimensions were significantly shorter in males than in females. The univariate analysis revealed that the operative time was significantly correlated with the inlet T diameter and that it tended to be correlated with the outlet T diameter and the inlet AP/T ratio. A multivariate analysis adjusted for operation-related factors revealed that the inlet AP/T ratio was the only independent risk factor for an extended operative time (p = 0.036). None of the pelvic dimensions were independent risk factors for increased blood loss.

Conclusion: The shape of the pelvic inlet may be useful for predicting the operative time.
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http://dx.doi.org/10.1007/s00595-017-1547-1DOI Listing
January 2018

Is preoperative spirometry a predictive marker for postoperative complications after colorectal cancer surgery?

Jpn J Clin Oncol 2017 Sep;47(9):815-819

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Background: Spirometry is a basic test that provides much information about pulmonary function; it is performed preoperatively in almost all patients undergoing colorectal cancer (CRC) surgery in our hospital. However, the value of spirometry as a preoperative test for CRC surgery remains unknown. The aim of this study was to determine whether spirometry is useful to predict postoperative complications (PCs) after CRC surgery.

Methods: The medical records of 1236 patients who had preoperative spirometry tests and underwent CRC surgery between 2005 and 2014 were reviewed. Preoperative spirometry results, such as forced vital capacity (FVC), one-second forced expiratory volume (FEV1), %VC (FVC/predicted VC) and FEV1/FVC (%FEV1), were analyzed with regard to PCs, including pneumonia.

Results: PCs were found in 383 (30.9%) patients, including 218 (56%) with surgical site infections, 67 (17%) with bowel obstruction, 62 (16%) with leakage and 20 (5.2%) with pneumonia. Of the spirometry results, %VC was correlated with PC according to logistic regression analysis (odds ratio, OR = 0.99, 95% confidence interval, CI = 0.98-0.99; P = 0.034). Multivariate analysis after adjusting for male sex, age, laparoscopic surgery, tumor location, operation time and blood loss showed that a lower %VC tends to be a risk factor for PC (OR = 0.99, 95% CI = 0.98-1.002; P = 0.159) and %VC was an independent risk factor for postoperative pneumonia in PCs (OR = 0.97, 95% CI = 0.94-0.99; P = 0.049).

Conclusions: In CRC surgery, %VC may be a predictor of postoperative complications, especially pneumonia.
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http://dx.doi.org/10.1093/jjco/hyx082DOI Listing
September 2017

Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice.

Cardiovasc Res 2017 Aug;113(10):1208-1218

Department of Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Vancouver, BC V5Z 1M9, Canada.

Aims: Although surfactant protein-D (SP-D) is a pneumoprotein that is predominantly synthesized by type II epithelial cells in the lung, individuals with increased circulating levels of SP-D are at an elevated risk of mortality from ischemic heart disease. Whether SP-D contributes directly to atherosclerosis is unknown. We determined the effects of SP-D gene deletion in a mouse model of atherosclerosis.

Methods And Results: SP-D knockout (KO) mice were crossed with hyperlipidemic and atherosclerosis-prone apolipoprotein E (ApoE) KO mice to generate SP-D/ApoE double knockout (DKO) mice. Mice were placed on a high-fat diet for 12 weeks beginning at 8 weeks of age. Compared with ApoE KO mice, SP-D/ApoE DKO mice had significantly less atherosclerosis with reduced macrophage accumulation, decreased local macrophage proliferation, and increased smooth muscle cell coverage in plaques. Interestingly, SP-D deficiency worsened hypercholesterolemia and induced obesity and insulin resistance but suppressed plasma interleukin-6 (IL-6) levels. SP-D deficiency also reduced blood monocytes and neutrophils counts in ApoE KO mice.

Conclusion: SP-D deficiency reduces atherosclerosis in part by decreasing the accumulation and proliferation of macrophages and by reducing IL-6 levels systemically. SP-D is a promising therapeutic target for cachectic COPD patients with elevated circulating SP-D levels who are at increased risk of cardiovascular morbidity and mortality.
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http://dx.doi.org/10.1093/cvr/cvx067DOI Listing
August 2017

The use of laparoscopic rectopexy to manage rectal prolapse with Pseudo-Meigs' syndrome in a 64-year-old female: a case report.

Clin Case Rep 2017 05 29;5(5):642-644. Epub 2017 Mar 29.

Department of Surgery Keio University School of Medicine Tokyo Japan.

We report a rare case of rectal prolapse with Pseudo-Meigs' syndrome in which laparoscopic bilateral oophorectomy and rectopexy were performed simultaneously and resulted in improved quality of life due to the loss of ascites and the repair of rectal prolapse. Laparoscopic surgery is feasible for rectal prolapse with Pseudo-Meigs' syndrome.
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http://dx.doi.org/10.1002/ccr3.918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412801PMC
May 2017

Non-alcoholic fatty liver disease fibrosis score predicts hematological toxicity of chemotherapy including irinotecan for colorectal cancer.

Mol Clin Oncol 2017 Apr 1;6(4):529-533. Epub 2017 Mar 1.

Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.

Liver dysfunction that may affect drug metabolism is a major concern in patients treated with chemotherapy. Thus, assessment of the degree of liver dysfunction is crucial for predicting the adverse events of chemotherapy. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive clinical scoring system constructed from routine clinical and laboratory variables. The aim of this study was to evaluate whether NFS was useful for predicting the adverse events of chemotherapy including irinotecan (CPT-11) for colorectal cancer. Between January, 2007 and May, 2013, a total of 87 patients with unresectable/recurrent colorectal cancer who received first-line chemotherapy including CPT-11 were reviewed. Demographic variables, including pretreatment NFS, were retrospectively collected from medical records. The primary outcome was the association between pretreatment NFS and adverse events, such as hematological and non-hematological toxicity, of chemotherapy including CPT-11. The median pretreatment NFS was 1.302 (range, 5.158-2.620). Pretreatment NFS was an independent risk factor for hematological toxicity in a multivariate analysis (coefficient=0.932, 95% CI: 0.083-1.781; P=0.031). Receiver operating characteristic curve analysis identified 0.347 as the optimal cut-off value associated with hematological toxicity. Using this cut-off, high NFS was found to be a significant risk factor for hematological toxicity (coefficient=2.019, 95% CI: 0.239-3.798, P=0.026), but not for non-hematological toxicity (P=0.546). Therefore, based on these results, NFS appears to be a significant predictor of hematological adverse events in chemotherapy including CPT-11 for colorectal cancer and it is a non-invasive, useful tool that may be used for determining regimens or doses of chemotherapy including CPT-11.
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http://dx.doi.org/10.3892/mco.2017.1177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374966PMC
April 2017

Comparison of Preoperative Inflammation-based Prognostic Scores in Patients With Colorectal Cancer.

Ann Surg 2018 03;267(3):527-531

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Objective: To evaluate the prognostic impact of the systemic inflammation score (SIS) in colorectal cancer (CRC) patients in comparison with a conventional inflammation-based score, the modified Glasgow Prognostic Score (mGPS).

Summary Background Data: The SIS, which is calculated based on the preoperative serum albumin level and lymphocyte-to-monocyte ratio, is a reported prognostic marker in clear-cell renal cell carcinoma. However, the utility of the SIS in CRC remains unclear.

Methods: The study involved 727 CRC patients who underwent curative resection between September 2005 and December 2011. The prognostic impact of SIS and mGPS was evaluated using survival analyses. The prognostic impact of each score was compared visually by means of time-dependent receiver operating characteristics analysis.

Results: The median age of the patients was 67 (interquartile range: 58-75) years. The TNM stage distribution was stage I, 29.8%; stage II, 33.6%; stage III, 30.3%; and stage IV, 6.3%. The median follow-up period was 5.61 years (interquartile range: 4.24-7.06). Multivariate analysis revealed that an increased SIS and mGPS were independent prognostic factors (SIS: P = 0.018; mGPS: P = 0.005, respectively). The time-dependent receiver operating characteristics curve of the SIS was superior to that of the mGPS throughout the observation period. The estimated area under the curve (AUC) of the SIS was significantly higher than that of the mGPS (7-yr survival: SIS 0.673, mGPS 0.605, P = 0.030).

Conclusions: The SIS is a novel prognostic factor in CRC patients. Additionally, the SIS is an alternative inflammation-based biomarker, which may improve the prediction of clinical outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000002115DOI Listing
March 2018

Laparoscopic totally extra-peritoneal hernia repair for bilateral Spigelian hernias and coincident inguinal hernia: A case report.

Int J Surg Case Rep 2016 30;28:169-172. Epub 2016 Sep 30.

Department of Surgery, Sanno Hospital, 8-10-16 Akasaka, Minato-ku, Tokyo 107-0052, Japan.

Introduction: Spigelian hernia (SH) is a rare ventral hernia occurring near the lateral border of the rectus muscle. The treatment remains controversial and depends on institutional expertise. Although laparoscopic surgery is a good adaptation for the repair of ventral hernias, only a few cases have been reported in the literature. Here, we report a case of totally extra-peritoneal (TEP) repair for bilateral SHs.

Presentation Of Case: A 74-year-old Japanese man presented with asymptomatic bulges in the right lower abdominal quadrant. On physical examination, the bulges were located to the right of the lateral border of the abdominal rectus muscle and the right inguinal region in an upright position. We diagnosed right SH and coincident homonymous ipsilateral inguinal hernia (IH) by abdominal computed tomography and planned a curative operation by laparoscopy. By first laparoscopic exploration, we found an asymptomatic SH to the left of the lateral border of the abdominal rectus muscle and performed TEP repair for all hernias. The second laparoscopic exploration after fixing the mesh in place revealed that the orifice of the right SH was scarred and stiffened by repeated prolapse. We finally eliminated the sac by ligation because of a fear causing of reduction en masse of the SH.

Discussion And Conclusion: The use of laparoscopy simplified the diagnosis and facilitates the subsequent repair of the hernia. TEP approach is the ideal treatment for the simultaneous laparoscopic repair of SH and IH.
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http://dx.doi.org/10.1016/j.ijscr.2016.09.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061312PMC
September 2016

Metabolic Tumor Volume and Total Lesion Glycolysis in PET/CT Correlate With the Pathological Findings of Colorectal Cancer and Allow Its Accurate Staging.

Clin Nucl Med 2016 Oct;41(10):761-5

From the Departments of *Surgery, and †Diagnostic Radiology, Keio University School of Medicine, Tokyo, Japan.

Introduction: PET/CT plays an important role in cancer diagnosis. Recently, novel metabolic parameters in PET/CT such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported to be diagnostic and prognostic biomarkers of various cancers. We evaluated the diagnostic value of these metabolic parameters in colorectal cancer (CRC).

Methods: The study included 138 patients who underwent surgical resection of CRCs between August 2012 and March 2014. The MTVs and TLGs of tumors were measured using various SUV thresholds. The diagnostic abilities of the metabolic parameters were analyzed using ROC curves and classification and regression trees.

Results: The AUCs of the MTVs and TLGs for predicting T stage (0.881-0.892) were significantly higher than the AUC of the SUVmax (0.824). In the M stage, the AUCs of MTVs and TLGs (0.688-0.723) were significantly higher than that of the SUVmax (0.606). Recursive partitioning applying classification and regression trees demonstrated that the optimal cutoff values of the most important variables for discriminating T, N, and M stages are MTV2.5 = 9.35 and 63.33 mL, TLG50% = 328.1, and TLG50% = 94.81, respectively.

Conclusion: Metabolic tumor volumes and TLGs in PET/CT are reliable diagnostic biomarkers. Using these parameters, more accurate preoperative diagnoses for CRC can be made.
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http://dx.doi.org/10.1097/RLU.0000000000001332DOI Listing
October 2016

The impact of hepatic fibrosis on the incidence of liver metastasis from colorectal cancer.

Br J Cancer 2016 06 9;115(1):34-9. Epub 2016 Jun 9.

Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan.

Background: The aim of this study was to clarify the influence of hepatic fibrosis on metachronous liver-specific recurrence in colorectal cancer (CRC) patients who underwent colorectal surgery with curative intent. Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who suffer from NASH is increasing because of the consumption of high-calorie diets. It remains unclear how much of an impact NASH and HF have on the development of liver metastasis in CRC.

Methods: Patients who underwent curative surgical resection for CRC between 2000 and 2011 were included in this study. We evaluated the progression of HF by the non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test results, age, body mass index, and diabetes mellitus. Patients were grouped according to high (fibrotic liver; FL) or low (normal liver; NL) NFS. The influence of HF on hepatic recurrence was assessed by survival analyses.

Results: A total of 953 CRC patients were enrolled, comprising 293 in stage I, 327 in stage II, and 333 in stage III. The patients included were categorised as FL (77) or NL (876). The hepatic recurrence rates were 5.3% in the NL group and 10.4% in the FL group (P=0.02), whereas the overall recurrence rates were 16.0% in the NL group and 20.7% in the FL group (P=0.03). The 5-year liver-specific recurrence-free survival rate in the FL group was significantly poorer than that in the NL group (FL 89.1%, 95% confidence interval (CI) 78.4-94.7 vs NL 96.0%, 95% CI 94.3-97.2, log-rank test P<0.01). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared with NL (HR=2.98, 95% CI 1.23-7.21; P=0.02).

Conclusion: HF is a valuable prognostic factor for hepatic recurrence after curative surgical resection of CRC.
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http://dx.doi.org/10.1038/bjc.2016.155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931372PMC
June 2016

Randomized phase II trial of TEGAFIRI (tegafur/uracil, oral leucovorin, irinotecan) compared with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) in patients with unresectable/recurrent colorectal cancer.

Int J Cancer 2016 Aug 23;139(4):946-54. Epub 2016 Apr 23.

Department of Surgery, Keio University School of Medicine, 35 Shinano-Machi, Shinjuku-Ku, Tokyo, 160-8582, Japan.

Irinotecan-based chemotherapy with bevacizumab is one of the first-line standard therapies for metastatic colorectal cancer (mCRC). TEGAFIRI (UFT/LV + irinotecan) is an irinotecan-based chemotherapy regimen. Currently, few clinical data regarding TEGAFIRI are available. This study evaluated the efficacy and safety of TEGAFIRI in Japanese patients with mCRC. This is a multicenter, randomized, phase II study. The major inclusion criteria were previously untreated patients with mCRC (age: 20-75 years, Eastern Cooperative Oncology Group performance status: 0-1). Eligible patients were randomly assigned (1:1) to receive either FOLFIRI ± bevacizumab or TEGAFIRI ± bevacizumab. The primary endpoint was progression-free survival (PFS). The secondary endpoints were response rate, overall survival, dose intensity and toxicity. From November 2007 to October 2011, 36 and 35 patients assigned to the FOLFIRI and TEGAFIRI groups were included in the primary analysis. No significant difference in PFS was observed between the groups {median PFS: TEGAFIRI 9.9 months [95% confidence interval (CI), 6.5-14.7], FOLFIRI 10.6 months [95% CI, 7.7-16.5]; Hazard ratio, 0.98, 95% CI, 0.57-1.66, p = 0.930}. The response rates in the FOLFIRI and TEGAFIRI groups were 56% and 66%, respectively. Relative dose intensity was similar between the groups. The most common Grade 3/4 adverse event was diarrhea (26%) in TEGAFIRI group and neutropenia (39%) in the FOLFIRI group. The results of the present study indicate that TEGAFIRI ± bevacizumab is an effective and tolerable first-line treatment regimen for mCRC.
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http://dx.doi.org/10.1002/ijc.30127DOI Listing
August 2016
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