Toshiharu Yamaguchi

Hokkaido Pharmaceutical University School of Pharmacy, Otaru, Hokkaido, Japan

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Publications (320)961.77 Total impact

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    ABSTRACT: Purpose: To evaluate the clinicopathological features of and prognosis associated with sporadic colorectal cancer (CRC) in Japanese patients younger than 40 years old. Methods: The subjects of this study were patients with sporadic stage 0-III CRC, who underwent curative resection between 2004 and 2012 at the Cancer Institute Hospital. Clinicopathological characteristics and survival were compared between the young (<40 years; n = 81) and older groups (≥40 years; n = 2257). Results: The median age was 36 years in the young group and 64 years in the older group. Young patients had a lower incidence of right-sided colon cancer (14 vs 28 %) and a higher incidence of rectal cancer (47 vs 32 %; P < 0.0001). The number of retrieved lymph nodes was significantly higher in the young group than in the older group (P = 0.0049). The young patients had similar overall survival and relapse-free survival to their older counterparts, except for overall survival in stage II patients (P = 0.0229). However, multivariate analysis indicated that age was not an independent prognostic factor for overall survival in patients with stage II CRC. Conclusions: Young Japanese patients with sporadic CRC have unique characteristics such as a high incidence of rectal cancer and similar pathological features; however, they appear to have comparable survival to older patients.
    No preview · Article · Jan 2016 · Surgery Today
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    ABSTRACT: Background and aims: Laparoscopic gastric resection is widely used for gastric submucosal tumors (SMTs). However, it is difficult to determine an appropriate resection line using only the laparoscopic approach. We developed a laparoscopic and endoscopic cooperative surgery (LECS) technique, by combining laparoscopic gastric resection with endoscopic submucosal dissection, and have used this procedure to resect gastric SMTs. The present study aimed to present this procedure and evaluate the safety and feasibility of this procedure for resecting gastric SMTs. Methods: This retrospective study included 100 patients who underwent LECS for SMTs at the Department of Gastroenterological Surgery, Cancer Institute, between June 2006 and November 2014. The demographics, tumor histopathological characteristics, and operative and follow-up data were reviewed. Results: Complete resection with negative surgical margins was achieved in all patients, and LECS was performed regardless of tumor location. The mean operation time was 174.3 minutes, with an estimated blood loss of 16.3 mL. In addition, the mean time until the initiation of oral intake was 1.4 days, and the mean postoperative hospital stay was 8.4 days. Moreover, no local or distant tumor recurrence was observed. The only severe adverse event was leakage, which was observed in 1 patient. Conclusions: LECS was performed with a reasonable operation time, low blood loss, and minimal adverse events. Therefore LECS is safe and feasible for resecting gastric SMTs.
    No preview · Article · Dec 2015 · Gastrointestinal endoscopy
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    ABSTRACT: Background The objectives of this study were to evaluate the incidence of and the risk factors for readmission after gastrectomy. Our hypothesis was that early discharge may be related to an increase in the incidence of readmission. Methods This was a retrospective, single-center, observational study of 1442 patients who underwent gastrectomy for stage I gastric cancer. The main outcome was the incidence of early readmission after gastrectomy, which was defined as an admission within 6 months after the first discharge day. A stepwise logistic regression analysis was conducted to identify the risk factors for readmission after gastrectomy. Results The surgical procedures performed were total gastrectomy in 217 patients (15.0 %), distal gastrectomy in 845 patients (58.6 %), pylorus-preserving gastrectomy in 342 patients (23.7 %), and proximal gastrectomy in 37 patients (2.6 %). The median hospital stay was 11 days, and there were 63 readmissions for a total of 56 patients (3.8 %). The main reasons for readmission were poor food intake in 14 patients (22.2 %), anastomotic stricture in nine patients (14.3 %), small bowel obstruction in eight patients (12.7 %), and an abdominal distension in seven patients (11.1 %). Endoscopic balloon dilation was performed for the nine patients with anastomotic stricture, drainage was needed for the four patients with an intra-abdominal abscess, and laparotomy was performed for one patient with adhesion-associated bowel obstruction. The long hospitalization during the primary admission and patients who underwent total gastrectomy were risk factors for readmission. Conclusions Patients with a long hospital stay after gastrectomy are at an increased risk of early readmission, which was likely related to the incidence of severe sequelae specific to gastrectomy.
    No preview · Article · Oct 2015 · Gastric Cancer
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    ABSTRACT: Background: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. Methods: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. Results: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. Conclusions: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755
    Full-text · Article · Sep 2015 · Gastric Cancer
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    ABSTRACT: Capecitabine plus oxaliplatin (CapeOx) ± bevacizumab therapy is associated with a high incidence of hand-foot skin reaction (HFSR), hindering treatment. However, timing of onset and risk factors remain unclear. This study examined the development of HFSR and risk factors for its exacerbation to a serious condition in CapeOx ± bevacizumab therapy. We retrospectively examined patients with colorectal cancer receiving CapeOx ± bevacizumab therapy between October 1, 2009, and March 31, 2012. The observation period was defined as lasting until completion of 8 cycles. The relationship between cumulative dose of capecitabine and cumulative proportion of patients developing HFSR was evaluated by Kaplan-Meier methods. Risk factors for exacerbation of HFSR to a serious condition were assessed by multiple logistic regression. Data for 203 patients were analyzed. For patients treated at cumulative capecitabine doses of 100 000 mg/m(2) and 200 000 mg/m(2), Grade 1 HFSR occurred in ≥80% and ≥90%, respectively, and moderate-to-severe HFSR (Grade 2+) occurred in ≥10% and ≥20%, respectively. Multivariate analysis showed significant associations with diabetes (odds ratio [OR] = 4.79; 95% confidence interval [CI] = 1.86-12.34; P = 0.001), concomitant use of bevacizumab (OR = 6.01; 95% CI = 2.20-16.41; P = 0.001), history of fluorinated pyrimidine administration (OR = 2.42; 95% CI = 1.10-5.33; P = 0.027), and early onset (within 21 days) of Grade 1 HFSR (OR = 3.78; 95% CI = 1.64-8.70; P = 0.001). HFSR in CapeOx therapy is a cumulative toxicity and risk of exacerbation to a serious condition increases with diabetes, concomitant use of bevacizumab, history of fluorinated pyrimidine administration, and onset of Grade 1 HFSR within 21 days. © The Author(s) 2015.
    No preview · Article · Jul 2015 · Annals of Pharmacotherapy
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    ABSTRACT: Hypothyroidism is one of the side-effects caused by regorafenib. In the Japanese subset of the CORRECT study, hypothyroidism developed in 1.5% of the patients, but was not grade 3 or higher in any patient. Regorafenib is an oral multi-kinase inhibitor that has the same mechanism of action as sunitinb. However, the reported incidence of sunitinb-related hypothyroidism varies widely, ranging from 16.0% in clinical trials to 35.4% in post-marketing surveillance studies. In general, symptoms of hypothyroidism include fatigue and dysphonia. Hyperthyroidism must, therefore, be appropriately managed in order to maintain patient quality of life and avoid a critical level of hypothyroidism. During the first cycle of treatment with regorafenib, the incidence of abnormal thyroid-stimulating hormone (TSH) elevation was 31.4%. Our results suggest that thyroid function tests should be performed from day 1 of treatment with regorafenib. It would be prudent to consider routine monitoring of thyroid function in all patients who receive regorafenib and to recommend endocrinological consultation as necessary. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    No preview · Article · Jul 2015 · Anticancer research
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    ABSTRACT: The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin. Eligible patients had received prior chemotherapy including oxaliplatin and irinotecan that achieved a response or stable disease followed by confirmed disease progression ≥6 months previously during prior oxaliplatin-based therapy. The primary endpoint was the disease control rate (DCR) after 12 weeks of treatment starting. The DCR was defined as the sum of patients with complete response, partial response, and stable disease. Thirty-three patients were enrolled. The median age was 62 (range: 35-77) years and the male/female ratio was 19/14. Eastern Cooperative Oncology Group performance status was 0 in 84.8%. Fourteen primary tumors were in the colon and 19 were in the rectum. All patients received modified FOLFOX6 as the protocol treatment. After 12 weeks of treatment starting, the DCR was 39.4% (95% confidence interval 21.8-57.0) and the response rate (complete response and partial response) was 6.1%. The median number of chemotherapy cycles was five and the median total dose of oxaliplatin was 425 mg/m(2). Median progression-free survival time was 98 days and median overall survival was 300 days. The incidence of grade ≥1 and grade ≥3 allergic reactions was 28.1% and 3.1%, respectively. The incidence of grade ≥1 and grade ≥3 peripheral sensory neuropathy was 53.1% and 0%, respectively. There were no other severe adverse events and no treatment-related deaths. Reintroducing oxaliplatin can be both safe and effective. This may be a salvage option for patients with metastatic colorectal cancer who achieved a response or stable disease with prior oxaliplatin-based therapy followed by disease progression ≥6 months previously during prior oxaliplatin-based therapy.
    Full-text · Article · Jun 2015 · Drug Design, Development and Therapy
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    ABSTRACT: Surgery is the only potentially curative strategy for patients who have Stage IV colorectal cancer (CRC) with resectable metastases, but relapse is common. Randomized trials of adjuvant 5-FU-based systemic chemotherapy have not demonstrated any benefit after resection of liver metastases. We evaluated the efficacy, safety, and tolerability of oxaliplatin-based adjuvant chemotherapy after curative resection of hepatic or extrahepatic metastases of CRC. We retrospectively studied data for 88 consecutive patients with Stage IV CRC who underwent curative resection of metastases followed by oxaliplatin-based adjuvant chemotherapy between March 2007 and June 2013. The 3-year relapse-free survival (RFS) rate was 54.0 %. There was no significant difference in 3-year RFS between patients with metastases confined to the liver (52.7 %) and patients with extrahepatic metastases (57.2 %). Multivariate analysis revealed that the site of the primary tumor (right-sided colon or left-sided colon/rectum) and the number of metastases (solitary or multiple) were predictors of RFS. Scheduled courses were completed in 80.7 % of the patients. Except for neutropenia (47.7 %), severe adverse events were observed in <5 % of patients. Oxaliplatin-based adjuvant chemotherapy could be an effective option for selected patients with Stage IV CRC after curative resection of hepatic or extrahepatic metastases, and is both safe and tolerable.
    No preview · Article · May 2015 · Cancer Chemotherapy and Pharmacology
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    ABSTRACT: Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival benefit in initially unresectable advanced CRC with concurrent metastatic lesions.
    Full-text · Article · May 2015 · OncoTargets and Therapy
  • Tomoyuki Irino · Naoki Hiki · Manabu Ohashi · Souya Nunobe · Takeshi Sano · Toshiharu Yamaguchi
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    ABSTRACT: Thermal injury and unexpected bleeding caused by ultrasonic scalpels can lead to fatal complications in laparoscopic gastrectomy (LG), such as postoperative pancreatic fistulas (POPF). In this study, we developed the "Hit and Away" protocol for optimal usage of the ultrasonic scalpel, which in essence involves dividing tissues and vessels in batches using the tip of the scalpel to control tissue temperature. To assess the effectiveness of the technique, the surface temperature of the mesocolon of female swine after ultrasonic scalpel activations was measured, and tissue samples were collected to evaluate microscopic thermal injury to the pancreas. In parallel, we retrospectively surveyed 216 patients who had undergone LG before or after the introduction of this technique and assessed the ability of this technique to reduce POPF. The tissue temperature of the swine mesocolon reached 43 °C, a temperature at which adipose tissue melted but fibrous tissue, including vessels, remained intact. The temperature returned to baseline within 3 s of turning off the ultrasonic scalpel, demonstrating the advantage of using ultrasonic scalpel in a pulsatile manner. Tissue samples from the pancreas demonstrated that the extent of thermal injury post-procedure was limited to the capsule of the pancreas. Moreover, with respect to the clinical outcomes before and after the introduction of this technique, POPF incidence decreased significantly from 7.8 to 1.0 % (p = 0.021). The "Hit and Away" technique can reduce blood loss and thermal injury to the pancreas and help to ensure the safety of lymph node dissection in LG.
    No preview · Article · Apr 2015 · Surgical Endoscopy
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    ABSTRACT: Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms among women and the third largest number among men. Many new methods of treatment have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2014 for treatment of colorectal cancer (JSCCR Guidelines 2014) have been prepared as standard treatment strategies for colorectal cancer, to eliminate treatment disparities among institutions, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding among health-care professionals and patients by making these guidelines available to the general public. These guidelines have been prepared as a result of consensuses reached by the JSCCR Guideline Committee on the basis of careful review of evidence retrieved by literature searches and taking into consideration the medical health insurance system and actual clinical practice in Japan. They can, therefore, be used as a guide for treating colorectal cancer in clinical practice. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions of the Guideline Committee, controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories, on the basis of consensus reached by Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2014.
    No preview · Article · Apr 2015 · International Journal of Clinical Oncology
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    ABSTRACT: The Maastricht, Asia-Pacific consensus guidelines strongly recommend eradication of Helicobacter pylori in patients who have a history of gastric cancer. This open-label, single-center, randomized controlled trial was conducted to investigate the appropriate timing of eradication for patients undergoing gastrectomy. One hundred and fifty patients scheduled to undergo gastrectomy were allocated to either a preoperative or a postoperative group. The eradication regimen was a common triple therapy: lansoprazole, amoxicillin, and clarithromycin. Patients in the preoperative group were treated with the regimen, followed by surgery, and patients in the postoperative group were treated after postoperative day 8. The primary end point was the proportion of patients achieving successful eradication in the remnant stomach. The definition of successful eradication was negativity in both the C13 urea breath test and for the antigen in feces at 6 months after surgery. Eight patients were excluded, and the remaining one hundred and forty-two, 70 in the preoperative group and 72 in the postoperative group, were included on an intention to treat basis. The procedures used were gastrectomy with Billroth I, Roux-en-Y, and pylorus-preserving gastrectomy in 18, 70, and 57 patients, respectively. The proportion of patients showing successful eradication hardly differed between the 2 groups, 68.6% vs 69.4% (p = 1.000) in the pre- and postoperative groups, respectively. Subgroup analysis also demonstrated no significant difference among the reconstruction methods used. Preoperative H pylori eradication therapy for gastric cancer patients scheduled for gastrectomy is not necessary, regardless of the planned reconstruction procedure. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · Journal of the American College of Surgeons
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    ABSTRACT: Background: Capecitabine plus oxaliplatin (XELOX) has been established as a first-line treatment for metastatic colorectal cancer. Adherence is particularly important with capecitabine to maintain appropriate curative effect. In this study, we monitored the adherence to capecitabine on XELOX treatment and investigated which factors might decrease compliance. Methods: The study included 242 consecutive patients who received XELOX treatment for metastatic colorectal cancer between October 2009 and March 2012. Adherence to capecitabine was checked by pharmacists with a patient-reported treatment diary at a pharmaceutical outpatient clinic. Adherence rate was defined as the number of times that a patient took capecitabine in a 14-day cycle/28 prescribed doses. We retrospectively surveyed median relative dose intensities of capecitabine and the factors deteriorating adherence across eight cycles from electronic patient records and examined differences in compliance rates according to age. Results: The study included 144 male and 98 female patients. The overadherence rate was 1.5% (n=23). The median adherence rate was 93.5% (n=242) in the first cycle of XELOX treatment, which gradually rose to 96.1% (n=148) in the eighth cycle. The median relative dose intensity of capecitabine was 79.2%. The main factors contributing to decreased adherence to capecitabine were diarrhea (22.5%, 352 instances) and nausea/vomiting (13.8%, 215 instances). The rate of missed dose was 12.1%. Analysis of adherence issues in relation to patient age showed a trend toward worse adherence to capecitabine therapy in the group of patients aged ≥80 years (hazard ratio =3.83; 95% confidence interval 2.48-5.91, P<0.001 versus 70-80 years group and versus <70 years group, chi-square test). Conclusion: Patient-reported adherence to capecitabine on XELOX treatment in clinical practice is high but adversely affected by side effects. Patients aged 80 years or more exhibit a significant decrease in compliance compared with younger patients.
    No preview · Article · Apr 2015 · Patient Preference and Adherence
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    ABSTRACT: The feasibility of gastrectomy with standard lymphadenectomy for patients over 85 years of age is not known. This study investigated short- and long-term outcomes and the tolerability of gastrectomy with standard lymphadenectomy for patients over 85 years with gastric cancer. Altogether, 77 patients aged over 85 years underwent gastrectomy with lymphadenectomy for gastric cancer at the Cancer Institute Hospital, Japan from May 2000 to February 2012. Postoperative short-term outcomes and survivals were analyzed retrospectively. Standard lymphadenectomy was defined according to the Japanese Gastric Cancer Association guidelines. Lymphadenectomy without splenectomy during total gastrectomy was called "reduced" lymphadenectomy. Distal gastrectomy was performed in 51 patients, total gastrectomy in 20, remnant total gastrectomy in 5, and proximal gastrectomy in 1 patient. Gastrectomy with standard lymphadenectomy was initially planned for 50 (64.9 %) patients and completed in 42 (54.5 %) patients. The other 8 patients underwent reduced lymphadenectomy because they required R1 or R2 resection. There were no deaths. The morbidity rate was 55.8 % overall and 54.8 % with standard lymphadenectomy. The most frequent complication was intestinal hypoperistalsis (29.9 %). The mean postoperative hospital stay was 19 days (range 10-70 days). The median overall survival time was 46.8 months. Coupled with comprehensive postoperative medical care due to the relative high morbidity risk, gastrectomy with standard lymphadenectomy for gastric cancer may be acceptable for relatively healthy patients over 85 years of age. Decisions to reduce the extent of lymphadenectomy during gastrectomy should not be based on advanced age alone.
    Preview · Article · Mar 2015 · Annals of Surgical Oncology
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    ABSTRACT: Early-onset gastric cancer is relatively rare. To evaluate the clinicopathological features and surgical outcome of young patients with gastric cancer, this retrospective comparative study was conducted. From 2000 to 2010, 4882 patients underwent surgery for gastric adenocarcinoma in our institution. A total of 136 patients under 40 years old were enrolled as the young group, and a total of 1435 patients aged between 60 and 69 were identified as the control group for this study. The patient's characteristics, pathological findings, surgical and clinical outcomes were reviewed, and the risk factors of recurrence were compared between the two groups. Among the young group, patients had significantly fewer comorbidities and postoperative complications. The patient proportion having 7 or more lymph node metastases was higher in the young group (25 %) than in the control group (16 %). The presence of lymph node metastasis was identified as a strong risk factor for recurrence (odds ratio = 4.31) in the young group according to the results of the step-wise logistic regression analysis. Although the disease-specific survival at stage II was relatively better in the young group (p = 0.0439) than in the control group, there were no significant differences in overall survival for all stages. Early-onset gastric cancer is likely to present lymph node metastases. The survival rate of gastric cancer in young patients was equivalent to that in patients in their 60s, which is the typical age at onset.
    No preview · Article · Mar 2015 · Gastric Cancer
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    ABSTRACT: A previous pivotal Phase III study (NO16966) demonstrated the benefit of the addition of bevacizumab (BV) to oxaliplatin-based regimens in metastatic colorectal cancer (MCRC). Our study evaluated the safety and efficacy of three oxaliplatin-based chemotherapy regimens (FOLFOX4 [intravenous twice-bolus and twice-infusional 5-fluorouracil/folinic acid plus oxaliplatin], mFOLFOX6 [intravenous once-bolus and once-infusional 5-fluorouracil/folinic acid plus oxaliplatin], and XELOX [capecitabine plus oxaliplatin]) plus BV in the first-line treatment of MCRC patients. Patients with MCRC who started treatment between June 2007 and September 2010 were evaluated in this retrospective cohort study. We also evaluated early objective tumor response (EOTR) within 12 weeks, which was defined as a relative change of ≥30% in the sum of the longest diameters of target lesions when compared with baseline. The primary study endpoints were progression-free survival (PFS) and response rate. A total of 185 patients received the following chemotherapy: FOLFOX4 + BV (FF4 arm, n=85), mFOLFOX6 + BV (FF6 arm, n=40), and XELOX + BV (XELOX arm, n=60). The overall response rates were 61.2%, 72.5%, and 75.0% (95% confidence interval: 50.6%-71.8%, 58.0%-87.0%, and 63.7%-86.3%). Median PFS was 18.0, 15.5, and 13.7 months, respectively (log-rank: P=0.254; data cut-off: May 2013). Patients with EOTR (n=117) had significantly better PFS than those without-EOTR (n=68) (17.5 versus 12.7 months, P=0.004). This study suggests that these three BV plus oxaliplatin-based treatments might have comparable benefit in terms of tumor response and PFS. Moreover, EOTR may be a predictive factor for PFS in patients with MCRC.
    Full-text · Article · Mar 2015 · OncoTargets and Therapy
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    ABSTRACT: Triweekly capecitabine plus irinotecan (XELIRI) is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV) as second-line chemotherapy for mCRC. Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m(2) twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m(2)), and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS). The recommended dose of irinotecan was determined to be 180 mg/m(2) in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients' characteristics were as follows (N=44): median age, 60 years (range 32-80); male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3-8.2 months), and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six patients and diarrhea in five patients. There were no other severe adverse events or treatment-related deaths. In mCRC patients with wild-type or heterozygous UGT1A1*6 or *28 genotype, biweekly XELIRI + BV is effective and feasible as second-line chemotherapy. Biweekly XELIRI + BV is considered a valid substitute for FOLFIRI + BV in mCRC.
    Full-text · Article · Mar 2015 · Drug Design, Development and Therapy
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    ABSTRACT: Laparoscopic total gastrectomy (LTG) is used for early gastric cancer (EGC) in the upper stomach. However, the incidences of postoperative anastomotic complications such as leakage and stricture remain high. This study investigated whether using a single-stapling technique (SST) instead of a hemi-double-stapling technique (HDST) for intracorporeal circular-stapled esophagojejunostomy could reduce anastomotic complications after LTG. This retrospective study included 136 patients with EGC treated by LTG with intracorporeal circular-stapled esophagojejunostomy. Originally, HDST was used for esophagojejunostomy in 71 patients (original group). Thereafter, the esophagojejunostomy procedure was modified, and SST was used in a further 65 patients (modified group). The impact of the anastomotic procedure (SST or HDST) on anastomotic complications after LTG was determined by uni- and multivariate analyses. The incidence of anastomotic complications was significantly lower in the modified group (7.7 %) than in the original group (22.5 %; P = 0.017). The frequency of anastomotic leakage was lower in the modified group (3.1 %) than in the original group (9.9 %), although the difference was not statistically significant. Meanwhile, the frequency of anastomotic stricture was significantly less common in the modified group (6.2 %) than in the original group (18.3 %; P = 0.032). Multivariate analysis showed that anastomotic procedure with SST was significantly associated with a lower rate of postoperative anastomotic complications (odds ratio [OR], 0.217; 95 % confidence interval [CI], 0.063-0.631; P = 0.004), as was the operation time (OR, 0.237; 95 % CI 0.082-0.667; P = 0.007). The use of SST for intracorporeal circular-stapled esophagojejunostomy could reduce anastomotic complications after LTG.
    Preview · Article · Feb 2015 · Annals of Surgical Oncology
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    ABSTRACT: Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev). We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings. Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E), thrombus >40 mm in diameter (S), thrombus involving the superior vena cava (C), and decreased blood flow (V). Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9%) by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%). Of these 56 patients, 11 (19.6%) received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%), as well as V in two (18.2%), S + V + C in one (9.1%), E + S + V in one (9.1%), E + C in one (9.1%), E in one (9.1%), and C in one (9.1%). All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%). Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%), but there were no treatment-related severe adverse events or deaths. Severe thromboembolism was not observed in the other 68 patients. Our anticoagulant protocol for asymptomatic thrombosis detected by Doppler ultrasound imaging was effective at preventing severe thromboembolism during continued treatment with Bev.
    Full-text · Article · Jan 2015 · OncoTargets and Therapy

  • No preview · Conference Paper · Jan 2015

Publication Stats

6k Citations
961.77 Total Impact Points

Institutions

  • 2015
    • Hokkaido Pharmaceutical University School of Pharmacy
      Otaru, Hokkaido, Japan
  • 2007-2015
    • Japanese Foundation for Cancer Research
      • Department of Urology
      Edo, Tōkyō, Japan
    • The University of Tokyo
      • Division of Surgery
      Edo, Tōkyō, Japan
  • 1987-2001
    • Kyoto Prefectural University of Medicine
      • • Division of Digestive Surgery
      • • Department of Surgery
      Kyoto, Kyoto-fu, Japan
  • 1980
    • Akita University Hospital
      Akita, Akita, Japan
  • 1979
    • Akita University
      Akita, Akita, Japan