Antibody response to 1.0 and 0.5 mL doses of an inactivated bacterial vaccine against bovine respiratory disease in young Holstein calves: a field trial.

Introduction: Early vaccination of cattle with an inactivated commercial bacterial vaccine against bovine respiratory disease has been reported to increase antibody production and can alleviate the disease. However, its dosage has been little investigated in young Holstein calves. This study addresses the need to establish guide values for vaccine dosage in these animals. Material and Methods: Healthy calves received an inactivated vaccine for Histophilus somni, Pasteurella multocida and Mannheimia haemolytica intramuscularly at the ages of 1 and 4 weeks. Administered vaccine doses were 1.0 mL for the primary and booster vaccinations (1.0 + 1.0 group), 0.5 mL for the primary and 1.0 mL for the booster vaccination (0.5 + 1.0 group), or 0.5 mL for both vaccinations (0.5 + 0.5 group). Results: Differences in the vaccine responses between the 1.0 + 1.0 group and 0.5 + 1.0 group were minor. However, the number of calves with a positive vaccine response to H. somni in the 0.5 + 0.5 group was less than half of that in the 1.0 + 1.0 and 0.5 + 1.0 groups. In logistic regression analysis, although the booster vaccination dose was positively correlated with seropositivity for H. somni, the primary vaccination dose was not correlated with vaccine response. The number of calves with positive vaccine responses to M. haemolytica was low even after booster vaccination regardless of the dose. Conclusion: The dose of 0.5 mL can be used for primary vaccinations in newborn Holstein calves, but 1.0 mL may be required for booster vaccinations.

16S rRNA nanopore sequencing for rapid diagnosis of causative bacteria in bovine mastitis.

The rapid identification of specific bacterial pathogens in bovine mastitis is crucial for appropriate antimicrobial treatment. Sequencing of 16S rRNA gene amplicons is a proven, useful strategy for diagnosing bacterial infections. In this study, the use of 16S rRNA analysis with nanopore sequencer for the rapid identification of causative bacteria in bovine mastitis, was evaluated. DNA was extracted from 122 milk samples from cattle with suspected mastitis based on clinical symptoms. 16S rRNA gene amplicon sequencing was conducted using a nanopore sequencer. The efficacy of bacterial identification was verified by comparison with conventional culture methods. Nanopore sequencing identified the causative bacteria with high accuracy within approximately 6 h from the time of sample collection. When the major causative bacteria of bovine mastitis (Escherichia coli, Streptcoccus uberis, Klebsiella pneumoniae, and Staphylococcus aureus) were detected by nanopore sequencing, 98.3% of the results were consistent with identification through conventional culturing methods. 16S rRNA gene analysis using a nanopore sequencer enabled the rapid and accurate identification of bacterial species in bovine mastitis.

Field Trial of Antibody Response To Inactivated Bacterial Vaccine in Young Holstein Calves: Influence of Animal Health Status.

Introduction: Bovine respiratory disease (BRD) is one of the primary causes of death in young calves. Vaccination against infection by the common bacteria causing BRD is possible; however, the physical condition of the young calves that enables antibody production when stimulated by early immunisation remains to be elucidated. Material and Methods: Healthy young female Holstein calves on a commercial dairy farm were fed a colostrum replacer and administered primary and booster immunisations with an inactivated vaccine against the bacterial pneumonia agents Histophilus somni, Pasteurella multocida and Mannheimia haemolytica. At each immunisation, the body weight and height at the withers were measured and the body mass index (BMI) was calculated. Blood was sampled immediately before immunisation and 3 weeks following the booster. The calves were divided into positive and negative groups based on the antibody titre at the final blood sampling. Maternal antibody titres at the primary immunisation and BMI, nutritional status and oxidative stress at both immunisations were compared between the two groups. Results: Antibody titre at the primary and BMI at both immunisations were significantly higher in the positive than in the negative group (P < 0.05). Additionally, serum gamma globulin was significantly higher in the positive group (P < 0.05), indicating a strong correlation between maternal antibody and serum gamma globulin levels. Conclusion: Elevated maternal antibody titre and higher BMI are positive factors for successful early immunisation, for which suitable colostrum may also be fundamental in young calves administered inactivated vaccines.

Effects of intra-articular inoculation with Mycoplasma bovis on immunological responses in calf joints.

Mycoplasma arthritis that caused by Mycoplasma bovis exhibit severe lameness. This disease is difficult to cure with antibiotics, but the detailed pathological mechanisms have not been fully clarified. In this study, we examined the effects of intra-articular inoculation with M. bovis on immunological responses in calf joints. We inoculated three calves each with M. bovis or phosphate buffer saline (control) into the right stifle joint and dissected them at 15 days postinoculation. Mycoplasma bovis-inoculated calves exhibited swelling of the stifle joint, increases in synovial fluid, fibrin deposition, and cartilage thinning. Intracellular M. bovis was detected in synovial tissues analyzed by immunohistochemistry and transmission electron microscopy. Messenger RNA expressions of interleukin (IL)-1ß, IL-6, IL-8, IL-12p40, and IL-17A in synovial fluid cells and synovial tissues from M. bovis-inoculated calves were significantly higher than those from control calves. Protein levels of these cytokines in synovial fluid from M. bovis-inoculated calves were markedly higher than those from control calves. Our study clarified that inoculation with M. bovis into the stifle joint induced the production of inflammatory cytokines by synovial fluid cells and synovial tissues, causing a severe inflammatory response in joints. Additionally, M. bovis could invade cells in synovial tissues, which may have aided it in evading antibiotics and host immune surveillance.

Aerobic Composting and Anaerobic Digestion Decrease the Copy Numbers of Antibiotic-Resistant Genes and the Levels of Lactose-Degrading Enterobacteriaceae in Dairy Farms in Hokkaido, Japan.

Efficient methods for decreasing the spread of antimicrobial resistance genes (ARGs) and transfer of antimicrobial-resistant bacteria (ARB) from livestock manure to humans are urgently needed. Aerobic composting (AC) or anaerobic digestion (AD) are widely used for manure treatment in Japanese dairy farms. To clarify the effects of AC and AD on antimicrobial resistance, the abundances of antimicrobial (tetracycline and cefazolin)-resistant lactose-degrading Enterobacteriaceae as indicator bacteria, copy numbers of ARGs (tetracycline resistance genes and ß-lactamase coding genes), and concentrations of residual antimicrobials in dairy cow manure were determined before and after treatment. The concentration of tetracycline/cefazolin-resistant lactose-degrading Enterobacteriaceae was decreased over 1,000-fold by both AC and AD. ARGs such as tetA, tetB, and bla TEM were frequently detected and their copy numbers were significantly reduced by ∼1,000-fold by AD but not by AC. However, several ARG copies remained even after AD treatment. Although concentrations of the majority of residual antimicrobials were decreased by both AC and AD, oxytetracycline level was not decreased after treatment in most cases. In addition, 16S rRNA gene amplicon-based metagenomic analysis revealed that both treatments changed the bacterial community structure. These results suggest that both AC and AD could suppress the transmission of ARB, and AD could reduce ARG copy numbers in dairy cow manure.

Comparison of distal forelimb conformations between Japanese Black and Holstein-Friesian newborn calves.

Flexural and hyperextension deformities are congenital problems in calves. We, therefore, aimed to investigate the distal limb conformation in 1 day- and 28-day-old female Holstein-Friesian (HF) calves (n=21), male Japanese Black (JB) calves (n=15), and female JB calves (n=15). The claw angle of the forelimb dorsal claw wall in a standing position and recorded other parameters, including body weight, withers height, circumference of forelimbs, and flexor tendon thickness in the forelimbs, were measured and compared these between the three groups. At 1 day old, the mean claw angles were 51.1° in female HF calves, 47.0° in male JB calves, and 41.8° in female JB calves; the 95% confidence intervals (CIs) of the claw angles showed large distributions in all three groups. One female HF and one male JB calves showed mild flexural deformity, whereas four JB calves showed hyperextension deformity. At 28 days old, the mean claw angles were 51.7° in female HF calves, 51.2° in male JB calves, and 48.4° in female JB calves; the 95% CIs of the claw angles showed smaller distributions than those at 1 day old in all groups. For all groups, the limb deformities had improved without treatment at 28 days old. As a feature of the breed, female JB calves were apt to show hyperextended deformities inversely proportional to the body weight. These limb deformities healed spontaneously and were thought to be physiological.

Inflammatory cytokine mRNA and protein levels in the synovial fluid of Mycoplasma arthritis calves.

Bovine Mycoplasma arthritis (MA) is caused by Mycoplasma bovis and exhibits severe clinical symptoms. However, the pathophysiology of bovine MA is incompletely understood. In this study, we examined the cytokine mRNA expression of synovial fluid (SF) cells and cytokine concentrations in the SF of MA calves. The SF was isolated from five clinically healthy (control) and seven MA calves. mRNA and protein levels of interleukin (IL)-1ß, IL-6, IL-8, IL-12, and IL-17 in the SF from MA calves were significantly higher than those from control calves. Our results indicate that SF cells produce inflammatory cytokines, which mainly contribute to the severe inflammatory response in the joints of the MA calves.

Changes in mRNA of immune factors expressed by milk somatic cells of Holstein cows with hypocalcemia after calving.

Changes in immune factors expressed by milk somatic cells from Holstein cows with hypocalcemia after calving were investigated in this study. Fourteen multiparous Holstein cows after their 3rd or 4th calving in one farm were used. The cows were divided into 2 groups: 7 cows needing treatment due to onset of hypocalcemia (hypocalcemia group; age = 5.53 ± 0.27 years, parity = 3.14 ± 0.14) and 7 cows without health problems (control group; age = 5.88 ± 0.31 years, parity = 3.57 ± 0.26). Milk samples were collected aseptically using a cannula and mRNA of immune factors expressed by milk somatic cells were analyzed. Milk samples (50 mL) were collected from the right rear mammary gland of cows before milking at day 1 and weeks 1, 2, 4, and 8 after calving. All milk samples showed a negative reaction to the California Mastitis Test. Levels of relative interleukin (IL)-6 and cathelicidin in the hypocalcemia group were lower than those in the control group in weeks 1 to 8. A significant difference in relative IL-6 levels was found in week 4 (P < 0.05). These results suggest that levels of IL-6 expressed by milk somatic cells may be affected by hypocalcemia in dairy cows.

Dans la présente étude les modifications des facteurs immunitaires exprimées par les cellules somatiques du lait de vaches Holstein présentant une hypocalcémie après le vêlage ont été examinées. Quatorze vaches Holstein multipares après leur 3e ou 4e vêlage provenant d'une ferme ont été utilisées. Les vaches ont été réparties en deux groupes : sept vaches nécessitant un traitement en raison de l'apparition d'une hypocalcémie (groupe hypocalcémie; âge = 5,53 ± 0,27 ans, parité = 3,14 ± 0,14) et sept vaches sans problème de santé (groupe témoin; âge = 5,88 ± 0,31 ans, parité = 3,57 ± 0,26). Des échantillons de lait ont été prélevés de manière aseptique à l'aide d'une canule et l'ARNm des facteurs immunitaires exprimés par les cellules somatiques du lait a été analysé. Des échantillons de lait (50 mL) ont été prélevés dans la glande mammaire arrière droite des vaches avant la traite au jour 1 et aux semaines 1, 2, 4 et 8 après le vêlage. Tous les échantillons de lait ont montré une réaction négative au California Mastitis Test. Les niveaux relatifs d'interleukine (IL)-6 et de cathélicidine dans le groupe hypocalcémie étaient inférieurs à ceux du groupe témoin au cours des semaines 1 à 8. Une différence significative des taux relatifs d'IL-6 a été observée à la semaine 4 (P < 0,05). Ces résultats suggèrent que les taux d'IL-6 exprimés par les cellules somatiques du lait peuvent être affectés par l'hypocalcémie chez les vaches laitières.(Traduit par Docteur Serge Messier).

Flexor tendon transection and post-surgical external fixation in calves affected by severe metacarpophalangeal flexural deformity.

This study aimed to evaluate the transection of superficial digital flexor tendon (SDFT) and deep digital flexor tendon (DDFT) in calves with severe metacarpophalangeal flexural deformities (MPFD). The study comprised 17 forelimbs of 10 calves that were diagnosed at the Animal Medical Centre, Rakuno Gakuen University. The calves were treated via transection of the SDFT and DDFT with retention of the suspensory ligament, followed by external fixation according to a post-surgical gait test. The post-procedural prognosis was determined at 14 days post-surgery. Of the 17 limbs, 14 (82%) achieved non-lameness and a good prognosis. Surgical complications were not observed in any treated calves. The transection of SDFT and DDFT is an effective first-line surgical option for calves with severe MPFD.

Field Trial of Primary and Booster Dose of Inactivated Vaccine Against Bovine Respiratory Bacteria in Young Holstein Calves.

INTRODUCTION: The objective of this research was to evaluate the antibody response to multiple doses of an inactivated mixed vaccine against Histophilus somni, Pasteurella multocida, and Mannheimia haemolytica, and to investigate the influence of age at time of vaccination in the field. MATERIAL AND METHODS: Healthy female Holstein calves received the vaccine at the age of 5-12 days and 2, 3, or 4 weeks later in the first experiment or at 1, 2, or 3 weeks of age and 4 weeks later in the second. Blood samples were collected at each vaccination and 3 weeks after the booster dose. Based on the antibody titres after the vaccinations, calves were divided into positive and negative groups for each of the bacteria. Calves in the control group were vaccinated only once at the age of 19-26 days. RESULTS: Antibody titres against H. somni and P. multocida were significantly increased by the booster. After the second vaccinations, the titres against each bacterium were higher than those of the control group, and the M. haemolytica-positive percentage in calves with high maternal antibody levels (MAL) exceeded that in calves with low MAL. In the first experiment, a majority of the M. haemolytica-positive calves tended to have received the primary dose at seven days of age or older. CONCLUSION: A booster dose of the inactivated bacterial vaccine in young Holstein calves increased antibody production and overcame the maternal antibodies. Calves should be vaccinated first at seven days of age or older.

Relationship Between mRNA of Immune Factors Expressed by Milk Somatic Cells and Bacteria Present in Healthy Lactating Holstein Cows.

INTRODUCTION: The characteristics of immune factors in somatic cells from lactating dairy cows and their association with commensal bacteria in normal milk have not been clarified. This study investigated the relationship between the pathogenic bacteria in milk and somatic cell immune factors in healthy lactating cows. MATERIAL AND METHODS: In total 44 healthy Holstein cows were studied on one farm. Milk samples were collected aseptically using a cannula and these samples were cultured for detection of bacteria and analysis of mRNA of immune factors expressed by somatic cells. Cows were divided into two groups based on the microbial status of their milk samples: 12 cows showed bacteria in cultures (positive group), and the other 32 cows did not (negative group). RESULTS: The mRNA levels of IL-6, lactotransferrin, and cathelicidin expressed by somatic cells after milking decreased significantly compared to those before milking in both groups (P < 0.05). There were significantly lower mRNA levels of IL-6 and cathelicidin in the positive group compared to those in the negative group before milking. CONCLUSION: These results suggest that mRNA levels of IL-6 and cathelicidin expressed by the somatic cells may be affected by the presence of bacteria in healthy lactating dairy cows.

A case report of intracholecystic papillary neoplasm of the gallbladder resembling a submucosal tumor.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) is defined as papillary tumors detected macroscopically in the gallbladder. We report a case of ICPN which exhibited the atypical form like a submucosal tumor. CASE PRESENTATION: A 70-year-old man was admitted to our hospital because of hepatic disorder. Computed tomography and magnetic resonance imaging showed irregular thickening of the wall within the gallbladder fundus. Because the lesion might have been malignant, we performed laparoscopic cholecystectomy and liver bed resection. Macroscopic findings showed the mucosal surface of the tumor was smooth, and its form was similar to that of a submucosal tumor. Histopathological examination revealed papillary tumors within the mass with low-grade dysplasia; therefore, we diagnosed ICPN. CONCLUSION: In the present case, ICPN was resembling a submucosal tumor macroscopically because the tumors arose into the Rokitansky-Aschoff sinus and the adenomyomatous hyperplasia was merged with the ICPN. It is necessary to consider the possibility of tumor lesions within adenomyomatous hyperplasia.

Enhanced karyopherin-α2 expression is associated with carcinogenesis in patients with intraductal papillary mucinous neoplasms.

BACKGROUND/OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) can become malignant. Karyopherin-α2 (KPNA2) plays a central role in nucleocytoplasmic transport and is associated with various types of cancer. The current study examined pancreatic KPNA2 expression in cancer patients and evaluated its association with clinicopathological factors, cancer cell proliferation. METHODS: KPNA2 expression was investigated by immunohistochemistry in 40 surgically resected IPMN samples and its association with clinicopathological factors and Ki-67 expression were examined. RESULTS: Eighteen IPMN samples (45% of patients) showed positive KPNA2 expression. KPNA2 expression levels in IPMN tissue with invasive carcinoma were significantly higher than those in adjacent normal tissues and in IPMN tissue with low-to high-grade dysplasia. KPNA2 expression correlated with pathological malignancy and Ki-67 labeling index and KPNA2 and Ki-67 expression was co-localized in nuclei. E2F were co-localized with KPNA2 in the IPMN tissues with high expression of KPNA2. KPNA2 expression was enhanced in the invasion front and in proliferating Ki-67-positive cells. In addition, KPNA2 expression in IPMN tissues was associated with older age, dilation of main pancreatic duct diameter, the presence of nodules, and histological type. CONCLUSION: KPNA2 expression is associated with carcinogenesis of IPMN through the adenoma-carcinoma sequence.

Fauna of Cerambycidae (Insecta: Coleoptera) in Komaba Campus of the University of Tokyo, a highly urbanised area in Japan.

Urban green spaces play an important role in maintaining urban biodiversity in the Tokyo Metropolis, Japan. Plant-dependent insect assemblages such as Cerambycidae, in particular, are likely influenced by the existence of green spaces in Tokyo's urbanised environments. This study is the first comprehensive inventory of the cerambycid fauna in the Komaba Campus of the University of Tokyo. A cerambycid assemblage composed of a total of 25 species was recorded within the Komaba Campus site and compared to cerambycid assemblages in nine other green spaces distributed throughout Tokyo. The results indicated that the species number in the campus was similar to that recoded in a similar-sized green space in coastal Tokyo. Fewer cerambycid species were, however, found at the campus site than in larger-sized green spaces within Tokyo. Moreover, species compositions in urbanised areas were markedly different from those in suburbanised parks, mountains and forests within Tokyo.

Control of primary lesions using resection or radiotherapy can improve the prognosis of metastatic colorectal cancer patients.

BACKGROUND: Control of the primary lesions in metastatic colorectal cancer (mCRC) is still controversial. For rectal cancer patients, not only resection but also irradiation is expected to provide palliative effects. We investigated the effects of resection and irradiation of primary lesions (local control) on the prognosis of mCRC patients. PATIENTS: Forty-seven patients with mCRC at our institute were examined, with 34 in the local controlled group and 13 in the uncontrolled group. RESULTS: The median survival time (MST) of the local controlled and uncontrolled groups were 2.90 and 1.39 years (P = 0.028). Cox proportional hazard regression analysis showed that local control was an independent prognostic factor (P < 0.05). The patients who underwent primary lesion resection had significantly longer MST (2.90 vs. 1.39 years, P = 0.032) than those in the uncontrolled group. In rectal cancer patients, the patients who underwent irradiation to control the primary lesions had a significantly longer MST than the uncontrolled patient group (1.97 vs. 1.39 years, P = 0.019). CONCLUSIONS: Local control of primary lesions may improve the prognosis in mCRC patients. In rectal cancer patients with metastasis, not only resection but also irradiation of the primary lesions may be a useful therapeutic strategy. J. Surg. Oncol. 2016;114:75-79. © 2016 Wiley Periodicals, Inc.

Establishment of a novel method to evaluate peritoneal microdissemination and therapeutic effect using luciferase assay.

Peritoneal dissemination is a major cause of recurrence in patients with malignant tumors in the peritoneal cavity. Effective anticancer agents and treatment protocols are necessary to improve outcomes in these patients. However, previous studies using mouse models of peritoneal dissemination have not detected any drug effect against peritoneal micrometastasis. Here we used the luciferase assay to evaluate peritoneal micrometastasis in living animals and established an accurate mouse model of early peritoneal microdissemination to evaluate tumorigenesis and drug efficacy. There was a positive correlation between luminescence intensity in in vivo luciferase assay and the extent of tumor dissemination evaluated by ex vivo luciferase assay and mesenteric weight. This model has advantages over previous models because optimal luciferin concentration without cell damage was validated and peritoneal microdissemination could be quantitatively evaluated. Therefore, it is a useful model to validate peritoneal micrometastasis formation and to evaluate drug efficacy without killing mice.

KPNA2 over-expression is a potential marker of prognosis and therapeutic sensitivity in colorectal cancer patients.

BACKGROUND: Karyopherin α 2 (KPNA2) is a member of the Karyopherin α family and has recently been reported to play an important role in tumor progression. The aim of the current study was to elucidate the clinicopathological significance of KPNA2 over-expression in colorectal cancer (CRC). PATIENTS AND METHODS: KPNA2 expression was evaluated by immunohistochemistry in 122 surgically resected CRC and 13 biopsy specimens obtained at colonoscopy during screening for preoperative hyperthermochemoradiation therapy (HCRT). The association between KPNA2 expression and clinicopathological features and preoperative HCRT efficacy were examined. RESULTS: The high and low KNPA2 expression groups were comprised of 91 (74.6%) and 31 CRC patients, respectively. A significant association was observed between high expression and lymphatic invasion (P = 0.0245). KPNA2 high expression group had decreased overall survival (P = 0.00374). Multivariate analysis demonstrated high KPNA2 expression was independently associated with poor prognosis. Histological examinations revealed 11 (84.6%) and 2 (15.4%) of cases were KPNA2 positive and negative, respectively. Pathological complete response (pCR) was observed in 9.1% of KPNA2-positive cases and 100% of KPNA2-negative cases. CONCLUSION: High KPNA2 expression was found to be associated with poor prognosis and resistance to HCRT.

Inventory of the Heteroptera (Insecta: Hemiptera) in Komaba Campus of the University of Tokyo, a highly urbanized area in Japan.

BACKGROUND: The Heteroptera, or true bugs, forms one of the major insect groups with respect to the very diverse habitat preferences, including both aquatic and terrestrial species, as well as a variety of feeding types. The first comprehensive inventory of the Heteroptera at Komaba Campus of the University of Tokyo, or an urban green space in the center of the Tokyo Metropolis, Japan, was conducted. NEW INFORMATION: A total of 115 species in 29 families of the suborder Heteroptera were identified. The area had a high species richness compared with other urbanized and suburbanized localities in Tokyo. The campus is found to show a substantial difference in heteropteran species compositions, despite being close to the other localities surrounded by highly urbanized zones in central Tokyo.

Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.

Addition of Bevacizumab to First-Line Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND/AIMS: We evaluated the efficacy and safety of bevacizumab for metastatic colorectal cancer patients. METHODOLOGY: All unresectable metastatic colorectal cancer patients who began receiving bevacizumab at participating facilities from 2006 to 2011 were retrospectively analyze to determine the safety and efficacy. The primary end points were Progression Free Survival (PFS) and Overall Survival (OS). The secondary end points were adverse events. RESULTS: A total of 101 patients were enrolled in the study. The primary tumor site was the colon in 53 patients and the rectum in 48 patients. The most common metastatic sites were the liver (63.4%), lung (31%), and peritoneum (10%). In first-line therapy, 76 (75.2%) patients received the FOLFOX regimen. Among these patients, 33 (43.4%) patients received FOLFOX alone, and 43 (56.6%) received FOLFOX plus bevacizumab. The addition of bevacizumab to first-line chemotherapy was associated with increases in median PFS (12.5 vs. 6.0 months; P = .00001) and median OS (24.0 vs. 16.0 months; P = 0.0221). The risks of adverse events were not significantly increased with the addition of bevacizumab. CONCLUSIONS: The addition of bevacizumab to first-line therapy in CRC patients provided clinically significant patient benefit, including statistically significant improvement in OS and a favorable tolerability profile.