[A Case of Advanced Esophagogastric Junction Adenocarcinoma with Enlarged Lymph Node Metastases of the Middle Mediastinum and Intraperitoneal That Exhibited pCR by Preoperative SOX Therapy].

A 79-year-old man was diagnosed with esophagogastric junction adenocarcinoma, cT3N3M0, cStage Ⅲ, including enlarged lymph node metastases(Bulky N)in the middle mediastinum and intraperitoneal. A total of 2 cycles of S-1 plus oxaliplatin(SOX)was administered. After neoadjuvant chemotherapy, the primary tumor and enlarged lymph nodes had greatly decreased in size. Subsequently, thoracoscopic subtotal esophagectomy and reconstruction with a gastric tube were performed. Histopathological examinations showed no residual cancer cells in the primary lesion and dissected lymph nodes (pathological complete response). Preoperative chemotherapy containing SOX could be a useful treatment strategy for patients with esophagogastric junction adenocarcinoma with enlarged lymph node metastasis.

Multiple primary malignancies involving primary sporadic colorectal cancer in Japan: incidence of gastric cancer with colorectal cancer patients may be higher than previously recognized.

BACKGROUND: Improvement in the prognosis of colorectal cancer (CRC) patients has led to increasing occurrences of multiple primary malignancies (MPMs) alongside CRC but little is known about their characteristics. This study was undertaken to clarify the clinical and pathological features of MPMs, especially those at extra colonic sites, in patients with CRC. METHODS: We reviewed 1,111 patients who underwent operations for primary sporadic CRC in Saitama Medical Center, Jichi Medical University between April 2007 and March 2012. Two patients with familial adenomatous polyposis, one with hereditary non-polyposis colorectal cancer, two with colitic cancer, and any patients with metastasis from CRC were excluded. We compared the clinicopathological features of CRC patients with and without MPMs. As a control, we used a database compiled of patients with gastric cancer (GC) detected by mass screening performed in the Saitama Prefecture in Japan 2010 and compared these with CRC patients with synchronous GC. RESULTS: Multiple primary malignancies at extracolonic sites were identified in 117 of 1,111 CRC patients (10.5%). The median age was 68 (range, 29 to 96) versus 71 (50 to 92) (P < 0.001). The incidence of GC (44.4% (52 of 117)) was the highest of all MPMs. All CRC patients with GC were older than 57 years. Synchronous GC was detected in 26 patients. By contrast, out of 200,007 screened people, 225 people were diagnosed as having GC in the Saitama Prefecture. The age-standardized incidence of synchronous GC in CRC patients was significantly higher (0.53%) than in the control group (0.03%) (odds ratio, 18.8; 95% confidence interval, 18.6 to 19.0; P < 0.001). CONCLUSION: Patients with CRC who were older than 50 years preferentially developed GC synchronously and metachronously. Thus, this patient group should undergo careful perioperative screening for GC.

Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway associated with ulcerative colitis.

BACKGROUND & AIMS: TWEAK, a member of the tumor necrosis factor (TNF) superfamily, promotes intestinal epithelial cell injury and signals through the receptor Fn14 following irradiation-induced tissue damage and during development of colitis in mice. Interleukin (IL)-13, an effector of tissue damage in similar models, has been associated with the pathogenesis of ulcerative colitis (UC). We investigated interactions between TWEAK and IL-13 following mucosal damage in mice. METHODS: We compared patterns of gene expression in intestinal tissues from wild-type and TWEAK knockout mice following γ-irradiation. Intestinal explants from these mice were used to detect cell damage induced by IL-13 and TNF-α. Levels of messenger RNA for IL-13, TWEAK, and Fn14 were measured in mucosal samples from patients with UC. RESULTS: Based on gene expression analysis, TWEAK mediates γ-irradiation-induced epithelial cell cycle arrest and apoptosis. However, TWEAK alone did not induce damage or apoptosis of primary intestinal epithelial cells. On the other hand, exogenous IL-13 activated caspase-3 in naïve intestinal explants; this process required TWEAK, Fn14, and secretion of endogenous TNF-α which was mediated by ADAM17. Conversely, activation of caspase by exogenous TNF-α required IL-13, TWEAK, and Fn14. In mucosa from patients with UC, messenger RNA levels of IL-13, TWEAK, and Fn14 increased with level of disease severity. CONCLUSIONS: IL-13-induced damage of intestinal epithelial cells requires TWEAK, its receptor (Fn14), and TNF-α. IL-13, TNF-α, TWEAK, and Fn14 could perpetuate and aggravate intestinal inflammation in patients with UC.

Comprehensive analysis of chemokines and cytokines secreted in the peritoneal cavity during laparotomy.

We recently found that chemokine-driven peritoneal cell aggregation is the primary mechanism of postoperative adhesion in a mouse model. To investigate this in humans, paired samples of peritoneal lavage fluid were obtained from seven patients immediately after incision (preoperative) and before closure (postoperative), and were assayed for the presence of 27 cytokines and chemokines using multiplex beads assay. As a result, IL-6 and CCL5 showed the most striking increase during operation. Recombinant CCL5 or lavage fluid induced chemotaxis of human peripheral blood mononuclear cells. We propose that CCL5 is possibly involved in the mechanism of postoperative adhesion in humans.

Patient's appetite is a good indicator for postoperative feeding: a proposal for individualized postoperative feeding after surgery for colon cancer.

BACKGROUND: In modern postoperative management, early and enforced feeding has been implemented. The aim of this study is to determine the feasibility of individualized feeding according to the patient's appetite. METHODS: Patients who underwent elective surgery for colon cancer from January 2007 to December 2008 were studied. Liquid intake was allowed on the day of operation and solid normal meal (1800 Kcal) was served according to the recovery of appetite. RESULTS: Two hundred and nine patients were included. Open and laparoscopic surgeries were performed in 104 and 105 patients, respectively. Solid meal was started by the second postoperative day in 81.3% of patients. Intravenous drip infusion was completed within 1 day of the start of the solid meal in 86.6% of the patients and 182 out of 209 patients (87.1%) did not require drip infusion by the third postoperative day. There were no mortalities and readmission rate was 1.0% (2/209). CONCLUSION: The introduction of feeding according to the recovery of appetite was safe and feasible with no delay in establishing oral intake.

Diagnostic accuracy of CT colonography and optical colonoscopy evaluated using surgically resected specimens.

OBJECTIVE: The aim of this study was to clarify the diagnostic ability of CT colonography (CTC) using surgically resected specimens to avoid inaccuracy associated with optical colonoscopy (OC). SUBJECTS AND METHODS: CTC and OC were performed in 152 consecutive patients with colorectal cancer. Forty patients had simultaneous lesions other than the ones for which the surgery was intended, and these lesions were used as the gold standard. In 24 patients without stenosis, the sensitivity and positive predictive values (PPV) of CTC and OC were evaluated. In 16 patients with stenosis, the diagnostic ability of CTC for lesions located proximal to the stenosis was assessed. RESULTS: Sensitivity of CTC and OC was 81% and 66% (P = 0.16), and PPV was 90% and 100% (P = 0.13), respectively. For 22 lesions larger than 5 mm, the sensitivity of CTC and OCS was 96% and 91% (P > 0.50), and PPV was 100% and 100%, respectively. In patients with stenosis, sensitivity and PPV were 89% and 80%, respectively. These results were not significantly different from those in patients without stenosis. CONCLUSIONS: CTC is a reliable modality for the diagnosis of colorectal polyps. It is also useful to evaluate the colon proximal to severe stenosis which could not be observed by OC.

Promoter hypermethylation of tumor-related genes in peritoneal lavage and the prognosis of patients with colorectal cancer.

BACKGROUND AND OBJECTIVES: The predictive value of free cancer cells in the peritoneal fluid of patients with colorectal cancer (CRC) remain to be elucidated. The aim of this study was to determine the prognostic relevance of the methylation of tumor-related genes detected in the peritoneal lavage fluid (PLF) of patients undergoing a resection for CRC. METHODS: The promoter methylation pattern of four target genes, CDH1, CDKN2A (p16), MGMT, and APC, was examined in 51 primary CRC and corresponding matched PLF DNA. The relative methylation levels of these genes in primary CRC tissue and paired PLF were assessed by quantitative methylation-specific polymerase chain reaction (QMSP). RESULTS: An aberrant methylation of at least one gene was found in 45 of 51 (88%) primary tumors. In matched PLF specimens, the frequencies of aberrant promoter methylation detected for each marker were 16% for CDH1, 2% for p16, 4% for MGMT and 24% for APC. Patients with PLF demonstrating the methylation of more than one of these four target genes demonstrated significantly shorter relapse-free survival. CONCLUSIONS: These findings suggest that disseminated tumor cells in PLF detected by QMSP may correlate with the postoperative clinical course of patients undergoing curative surgery for CRC.

Trainee surgeons do not cause more conversions in laparoscopic colorectal surgery if they are well supervised.

INTRODUCTION: This study was designed to look at the conversion rates and morbidity associated with laparoscopic operations performed by trainee surgeons ascending the learning curve when they are well supervised by staff surgeons. METHODS: A review of 204 consecutive cases was performed. We defined experienced staff surgeons as those who have performed more than 300 laparoscopic resection cases. The trainee surgeons had less than 50 cases of experience during the study period. All operations were performed by the experienced staff surgeon or by the trainee surgeon with the staff surgeon as the first assistant and supervisor. RESULTS: A total of 204 laparoscopic resections for colorectal cancer were studied. The dissection was D3 in 73% (n = 149) of cases with a mean lymph node harvest of 19.4 nodes (range 1-56). The staff surgeons performed 90 cases and trainees performed 114 cases. Twenty-one cases (10.3%) required conversion. The overall morbidity rate was 17.6% and perioperative mortality rate was 1.5%. On bivariate analysis, trainee surgeons were not found to be significantly associated with a higher conversion risk. Multivariate analysis revealed that only the factor of T3 and above was an independent predictor of conversion (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.09-15.48). Multivariate analysis of risk factors for morbidity revealed that it was not conversion (OR 2.37; 95% CI, 0.86-6.76) but rectal surgery (OR 4.09; 95% CI 2.04-9.9) that was the independent risk factor of morbidity. CONCLUSIONS: Inexperienced surgeons do not cause more conversions or postoperative morbidity in laparoscopic colorectal surgery if they are well supervised. Conversion is not independently associated with increased postoperative morbidity.

Visceral obesity predicts surgical outcomes after laparoscopic colectomy for sigmoid colon cancer.

PURPOSE: This study was designed to assess whether visceral obesity is a more useful predictor of surgical outcomes compared with body mass index after laparoscopic colectomy. METHODS: A total of 133 consecutive patients who underwent elective laparoscopic colectomy for sigmoid colon cancer between April 2001 and April 2007 were included. Obesity was defined by visceral fat area > or = 130 cm(2) or body mass index > or = 25 kg/m(2), and the variables were compared for obese and nonobese patients. RESULTS: There were 68 (51.1 percent) obese patients according to visceral fat area and 27 (20.3 percent) according to body mass index. Using either definition, obese patients had a significantly longer operative time compared with nonobese patients. Patients classified as obese by visceral fat area had a significantly higher incidence of wound infection (20.6 vs. 4.6 percent; P = 0.006) and overall complication rates (32.4 vs. 12.3 percent, P = 0.006) compared with nonobese patients, whereas there was no significant difference when classified by body mass index. Postoperative hospital stay was significantly longer in obese patients compared with nonobese patients classified by visceral fat area (median 10.5 vs. 9 days; P = 0.007), whereas it was not statistically different when classified by body mass index. CONCLUSION: Visceral fat area is a more useful parameter than body mass index in predicting surgical outcomes after laparoscopic colectomy for sigmoid colon cancer.

Colonoscopic stigmata of 1 mm or deeper submucosal invasion in colorectal cancer.

PURPOSE: This study was designed to identify colonoscopic stigmata, indicating substantial invasion into the submucosa by T1 colorectal cancer with sessile morphology, including both flat and protruded types. METHODS: A total of 111 Tis or T1 colorectal cancers were studied retrospectively. The lesions were divided into two groups: Group A (n = 83), Tis or T1 cancers with <1 mm submucosal invasion; and Group B (n = 28), T1 cancers with a >/=1 mm submucosal invasion. Printed photographs of the lesions were reviewed by five experienced colonoscopists who were blinded to histology. Deep depression, irregular surface, ulceration or erosion, fold convergence, and spontaneous bleeding were independently evaluated. Findings considered present by three or more reviewers were defined as positive. Kappa analysis was used to measure inter/intraobserver variability. RESULTS: Positive rates of four findings but not fold convergence were significantly higher in Group B than in Group A. Irregular surface and spontaneous bleeding were significant independent predictors of >/=1 mm submucosal invasion, with diagnostic accuracies of 85.6 and 76.6 percent, respectively. Kappa analysis demonstrated fair-to-good inter/intraobserver agreement for spontaneous bleeding and fair-to-good intraobserver agreement for irregular surface. CONCLUSIONS: Irregular surface and spontaneous bleeding were colonoscopic stigmata, indicating >/=1 mm submucosal invasion in T1 colorectal cancer.

Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase partitioning.

OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of contaminants from OK-432 using Triton X-114 (TX-114)-water phase partitioning and examined an antitumor effect of the resulting preparation. OK-432 was subjected to TX-114 partitioning to give residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher and IL-10 production was lower than that of OK-432. In tumor-bearing mice model, administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN-gamma in mouse spleen cells in vitro. These results indicated that TX-114 partitioning removed some contaminants, which attenuates the antitumor effect, from OK-432 and increase the immunotherapeutic effects of OK-432.

For others: epistasis and the evolutionary survival of an extreme tail of the quantitative distribution of autistic assets.

The ongoing paradigm shift from the traditional qualitative dichotomy concept to the quantitative framework increases the necessity of an evolutionary implication and interpretation of the presence of a hypo-reproductive behavioral extreme (autism) with strong genetic contribution. As a theoretical challenge to explain the survival of the dimensional distribution of autistic traits, an epistasis-associated oscillation of fitness outcomes is proposed. In this hypothesis, an allele could contribute to the existence of both phenotypic extreme tails and the hypothesized genetic machinery (quantitative trait loci) for autism would necessarily be common in the entire human population. The postulated autism genes would allow autistics to enjoy autistic traits and assets and all of the residual non-autistic individuals could owe their social skills and reproductive advantages to the same autism genes. Importantly, the reported modest correlations between core autistic dimensions can be illustrated using unsynchronized epistatic pleiotropy.

Laying the foundation for wartime research: a comparative overview of science mobilization in National Socialist Germany, Japan, and the Soviet Union.

This chapter surveys wartime science mobilization within National Socialist Germany, Japan, and the Soviet Union to understand how each nation mobilized science resources for the war, how their approaches to mobilization differed, and how these approaches might be evaluated historically. Science mobilization in National Socialist Germany, in particular, has heretofore been characterized as a failure; however, such a view appears too simplistic and cannot account for the numerous advanced weapons and technological artifacts produced by the nation during the war. Both Germany and Japan operated under decentralized systems for science mobilization, whereas the Soviet Union imposed a highly-centralized authoritarian structure. These differed significantly from the organizational model of the United States, which has often been touted as the most "successful" of the belligerents. This essay attempts to evaluate the science mobilization efforts in these nations on their own terms, rather than comparing them directly with the American system.

Right axillary lymph node metastasis of carcinoma of the cecum with histologically proven cutaneous lymphatic invasion by carcinoma cells: a case report.

Axillary lymph node metastasis from colorectal carcinoma is extremely rare, and this scarcity hinders understanding of its pathogenesis and, thus, the application of appropriate management. Here, we present a case with axillary lymph node metastasis of cecal carcinoma associated with macroscopic invasion of the skin of the abdominal wall with histological evidence of such invasion, findings which support our hypothesis that the axillary lymph node metastasis developed via the lymph channels in the skin of the abdominal wall. A 76-year-old woman with cecal carcinoma (T4N1M0), complicated with an abdominal wall abscess, underwent right hemicolectomy with partial resection of the abdominal wall. Histology demonstrated multiple sites of lymphatic invasion in the skin. Two months later, an enlarged right axillary lymph node was noticed on CT, and an excisional biopsy was obtained, which later confirmed metastatic adenocarcinoma. This is the first case report of axillary lymph node metastasis of carcinoma of the cecum with histologically proven invasion via the lymphatic system in the skin. If axillary lymph node metastasis results from aberrant lymphatics due to invasion from an adjacent organ, and not the result of systemic malignant disease, it may be considered as a surgically curable pathology. Therefore, the authors advocate that patients with axillary lymph node metastasis should be evaluated with regard to the possibility of surgical curability.

Success rate of informed consent acquisition and factors influencing participation in a multicenter randomized controlled trial of laparoscopic versus open surgery for stage II/III colon cancer in Japan (JCOG0404).

INTRODUCTION: Successful completion of randomized controlled trials (RCT) is dependent on informed consent (IC) acquisition from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed IC acquisition. METHODS: A 30-institute RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage II/III colon cancer (JCOG0404: UMIN-CTR C000000105). The success rate of obtaining IC, which was supported by a DVD that helped patients understand this trial, was evaluated in eight periods between October 2004 and March 2009. In addition, reasons for failed IC acquisition were identified from questionnaires. RESULTS: A total of 1767 patients were informed of their eligibility for the trial, and 1057 (60%) were randomly assigned to either the laparoscopic surgery (n = 529) or open surgery (n = 528) group. The success rate of IC acquisition ranged from 50% to 62% in eight periods. The most common reasons for failed IC acquisition were anxiety/unhappiness about the randomization, patients' preference for one form of surgery, and strong recommendations from referring doctors or relatives. CONCLUSIONS: With the assistance of a DVD, high success rates of IC acquisition were obtained for an RCT of laparoscopic versus open surgery for stage II/III colon cancers. To obtain such a rate, investigators should make efforts to inform patients, their relatives, and referring doctors about the medical contributions a surgical RCT can make.

Reduced medical costs achieved after elective oncological colorectal surgery by early feeding and fewer scheduled examinations.

BACKGROUND: The aim of this study was to determine whether the early postoperative feeding protocol introduced in Western countries is feasible in Japanese patients who undergo oncological colorectal surgery, and to verify the necessity for scheduled postoperative blood samplings and X-rays, and to determine whether, as a result, these measures can lead to a reduction of medical costs and length of hospitalization. METHODS: Group I consisted of 17 patients who received the early postoperative feeding protocol. Group II consisted of 22 patients who received the traditional Japanese feeding protocol. In group I, postoperative clinical tests were performed only once, and in group II, examinations were performed routinely four times according to the traditional protocol. RESULTS: Most of the patients in group I (94.1%) tolerated the early feeding schedule. The length of postoperative hospitalization was significantly shorter in group I (11 +/- 2.96 days vs 18 +/- 4.96 days; P << 0.001). There was no significant difference in morbidity between the two groups. The number of times postoperative clinical tests were performed was significantly lower in group I. Significant reduction of postoperative medical costs was also shown in group I ($2028 US dollars +/- 53 vs $3177 US dollars+/- 1230; P << 0.001). CONCLUSIONS: This study revealed the safety and feasibility of early postoperative feeding and a single-examination protocol following elective oncological colorectal resection in Japanese patients, which led to a reduction in the length of postoperative hospitalization and in health-care costs. We emphasize the importance of meticulous postoperative monitoring of patients rather than the performance of scheduled postoperative examinations that have limited clinical significance.

Clinical significance of virtual colonoscopy (CT colonography) with special reference to polyp morphology.

BACKGROUND/AIMS: Computed tomographic colonography [virtual colonoscopy (VC)] is a new imaging method that may contribute to the detection of colorectal neoplasms. The aim of this study was to investigate the clinical significance of VC for the diagnosis of colorectal tumors with special reference to their morphology. METHODOLOGY: Sixteen patients with colorectal tumors were enrolled in this study. Colonic preparation was performed using magnesium sulfate, and scopolamine butylbromide was injected before air insufflation from the anus. VC was performed with an Aquilion multislice CT system (Toshiba) and Workstation M900 maximum (ZIO). The results were compared with those of conventional colonoscopy (CC). In six cases, total colonoscopy was not possible due to tumor stricture. RESULTS: The number of lesions detected by CC was 58; 48 early carcinomas/adenomas (group A) and 10 advanced carcinomas (group B). All group B lesions and 43.8% (21 lesions) of group A lesions were identified by VC. The specificity of VC for group A and B lesions was 45.8% and 100%, respectively. There was no significant difference in detection rate for group A lesions by subclassification according to their morphology: pedunculated; 22% (2/9), semipedunculated; 50% (6/12), sessile; 29% (4/14), superficially elevated; 56% (5/9), and superficially elevated morphology with central depression; 100% (4/4). The mean diameter of the lesions that were detected and not detected by VC was 7+/-8.0 mm (range: 3-30 mm) and 8+/-5.8 mm (range: 2-20 mm), respectively (P=0.90). CONCLUSIONS: Polyps with superficial morphology could be detected by VC as well as those with protuberant morphology. According to evidence that neither the morphology nor the size of a lesion was a significant factor for detection by VC, the authors consider that the diagnostic ability of VC may be improved by better preparation.

Colon cancer complicated by vascular and intestinal anomaly.

We present a case of colon cancer in a patient with an anomalous mesenteric artery, a middle mesenteric artery, associated with intestinal nonrotation. At surgery for such a rare case, an exact grasp of the feeding artery, the draining vein, and the lymphatic flow of the tumor is necessary to perform appropriate bowel resection and oncological nodal dissection. Selective angiography and preoperative endoscopic submucosal injection of India ink near the tumor were thought to be essential for surgical decision-making.

[Colorectal cancer].

Laparoscopic surgery for the cure of colorectal cancer has been a controversial issue. In this article summarizes the surgical procedures for right-and left-sided colon cancer as well as the results of randomized controlled trials (RCTs) while comparing the long-term results of laparoscopic and open surgery. The RCTs revealed no significant differences in overall survival rate between laparoscopic and open procedures. In future, laparoscopic surgery will be a standard operation for a certain group of patients with colorectal cancer. Adequate skills of the surgical team and appropriate patient selection are essential.

XELIRI regimen plus continuous treatment with bevacizumab is well-tolerated and effective in metastatic colorectal cancer patients in a second-line setting involving the sequential administration of XELOX and XELIRI.

The aim of the present study was to present a retrospective review of 42 metastatic colorectal cancer (mCRC) patients treated using the XELIRI regimen as second-line chemotherapy during the period between 2010 and 2012. Patients were treated with capecitabine, 1,600 (≥65 years) or 2,000 mg/m2 (<65 years), on days 1-15, 200 mg/m2 irinotecan (CPT-11) on day 1, with or without 7.5 mg/kg bevacizumab on day 1 and every 21 days. A total of 21 patients underwent XELIRI and 21 underwent XELIRI plus bevacizumab treatment. Fifteen patients received continuous administration of bevacizumab in the first- and second-line settings [bevacizumab beyond progression (BBP)+], whereas 27 patients did not receive the treatment (BBP-). Forty patients (95.2%), including all the patients in the BBP+ group, received sequentially administered XELOX and XELIRI regimens from the first- to the second-line setting. The disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were compared between the BBP- and BBP+ groups. The median relative dose intensity was similar (93.9% for capecitabine and 96.3% for CPT-11 in the BBP- group vs. 94.8% for capecitabine and 91.5% for CPT-11 in the BBP+ group). The DCR was 25.9% in the BBP- and 66.6% in the BBP+ groups (P=0.020). The median PFS was 3.5 months in the BBP- and 7.2 months in the BBP+ groups (P=0.028). The BBP+ group exhibited a higher median OS time compared to the BBP- group (12.5 months in the BBP- group vs. not reached in the BBP+ group; P=0.0267). The most common grade 3/4 adverse event (n≥20) was hypertension observed in the BBP+ group [three patients (20%)]: these three patients were well-controlled with a single antihypertensive drug. Treatment with sequentially administered XELOX and XELIRI regimens did not aggravate adverse events in the 40 patients. The results showed that the XELIRI regimen, involving continuous treatment with bevacizumab, was well-tolerated and effective as a second-line chemotherapy and sequentially administering XELOX and XELIRI was feasible and manageable for patients with mCRC.