Damage Control Surgery for Duodenal Ulcer Bleeding With Massive Hematoma and Perforation Due to Over-the-Scope Clip (OTSC).

Due to the advances in endoscopic technology, surgery for duodenal ulcer (DU) bleeding has decreased, although surgery is still necessary for more complicated cases. The concept of damage control surgery (DCS) has been established in the field of trauma, and a simple surgical approach may be preferable in serious cases such as uncontrolled DU bleeding. We present a successful case of bleeding with massive hematoma and perforation of the duodenum due to an over-the-scope clip that was treated by a less invasive surgical approach with consideration of the DCS.

Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis.

Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis.

Trans-anal Minimally Invasive Surgery Combined With a Robotic Anterior Approach for Sleeve Resection of a Huge Rectal Gastrointestinal Stromal Tumor.

Due to anatomical complexity, large rectal gastrointestinal stromal tumors (GISTs) in the pelvis at the anterior aspect often require extended abdominal surgery to obtain clear surgical margins. Here, we show our trans-anal minimally invasive surgery combined with a robotic anterior approach for a huge low rectal GIST that was widely in contact with the prostate and urethra. By performing lateral dissection first, we can identify the orientation of critical organs such as the prostate, urethra, and neurovascular bundles, facilitating anterior anorectal dissection without urethral injury. Although the combination with a transabdominal robotic approach was required because of firm inflammatory adhesion between the tumor and prostate, the preceding trans-anal dissection plane facilitated the robotic anterior dissection and contributed to achieving complete dissection with negative resection margins.

Comparison of changes in health-related quality of life between elderly and non-elderly patients undergoing elective surgery for colorectal cancer.

PURPOSE: Elderly people are thought to be more likely than their non-elderly counterparts to experience a decline in activities of daily living (ADL) and quality of life (QOL) due to the onset and treatment of disease. In this study, we investigated whether there was an age-related difference in changes in health-related QOL indices after surgical resection of colorectal cancer (CRC). METHODS: Patients who underwent elective surgery for primary CRC at our hospital between September 2017 and November 2021 were enrolled. Changes in QOL after surgery were evaluated after dividing the study population into a non-elderly (NE) group (younger than 75 years) and an elderly (E) group. A Short-Form 36-Item Health Survey was used as an index of QOL. The subscale and component summary scores before and 6 months after surgery were compared. RESULTS: Forty-seven patients were included in the E group and 166 patients were the NE group. The E group had significantly worse preoperative performance and physical status than the NE group. However, indices of physical function were not worsened after surgery in either group. In the NE group, there were significant decreases in role physical and role component summary scores and significant increases in general health, mental health, and mental component summary scores. In the E group, there were no significant changes in the subscale or component summary scores after surgery. CONCLUSION: Our study demonstrated elderly patient did not necessarily show a decline in QOL more than non-elderly patients after CRC surgery. Surgical resection for CRC should be considered even for elderly patients, while considering possible risk factors for worsening ADL and QOL.

Comparison of oncological outcomes between low anterior resection and abdominoperineal resection for rectal cancer: A retrospective cohort study using a multicenter database in Japan.

BACKGROUND: It remains controversial whether the abdominoperineal resection (APR) procedure itself has a negative impact on prognosis compared with sphincter-saving surgery (SSS). The purpose of this study was to investigate whether the operation type affects the prognostic outcome in rectal cancer using a multicenter database in Japan. METHODS: The study involved 2533 patients who underwent APR or SSS and were registered in the Japanese Society for Cancer of the Colon and Rectum database, which includes data from 74 centers, between 2003 and 2007. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). The secondary endpoints were local recurrence rate (LRR) and pathological radial margin (pRM) status. RESULTS: Multivariate analysis identified pathological tumor depth, lymph node status, and pRM status to be associated with oncological outcomes (OS, RFS, LRR). Although the oncological outcomes were worse after APR than after SSS in univariate analysis, there was no significant difference in OS (hazard ratio 1.08; 95% confidence interval [CI] 0.85-1.37) or RFS (hazard ratio 1.06; 95% CI 0.87-1.30) between APR and SSS. There was also no significant difference in LRR (odds ratio 1.11, 95% CI 0.70-1.77). Multivariate analysis showed that operation type was associated with positive pRM (odds ratio 3.13, 95% CI 0.18-0.56). CONCLUSIONS: There was no significant difference in oncological outcomes between APR and SSS for rectal cancer. The risk of positive pRM was higher for APR and performing radial margin-negative surgery is an important factor in improving the oncological outcomes of APR.

Phase 2 study of perioperative chemotherapy with SOX and surgery for stage III colorectal cancer (SOS3 study).

This phase 2 study evaluated the safety and efficacy of perioperative chemotherapy with S-1 plus oxaliplatin (SOX) for stage III colorectal cancer (CRC). Patients with stage III CRC received surgery after neoadjuvant chemotherapy (NAC; SOX 4 cycles) and adjuvant chemotherapy (AC; SOX 4 cycles). The primary endpoints were response rate and safety. We enrolled 30 patients. Their median age was 62 years (range: 43-87 years); 53% were women. They received a median of 4 cycles (range: 1-4) of NAC and a median 4 cycles (range: 0-4) of AC. Five patients interrupted NAC treatment because of toxicity (grade 3 diarrhoea [n = 1], grade 3 ileus [n = 1], and grade 3-4 thrombocytopenia [n = 3]). Patients' responses were complete responses: n = 2 (6.6%), partial responses: n = 21 (70%), stable disease: n = 6 (20.0%), and progressive disease: n = 1 (3.3%; response rate: 73.3%). Curative resection was performed in 29 patients. No patients showed anastomotic leakage. Five-year overall survival and disease-free survival were 83.3% and 76.7%, respectively (median follow-up time: 48 months). NAC using SOX regimen is safe and effective, and may lead to reduced local recurrence and distant metastasis. Long-term outcomes are awaited to evaluate further the efficacy of this strategy (UMIN000006790).

Transanal TME: new standard or fad?

Transanal total mesorectal excision (taTME) has been developed to overcome the difficulty of laparoscopic dissection and transection in the deep pelvis. TaTME has several clinical benefits over laparoscopic surgery, such as better exposure of the distal rectum and direct determination of distal resection margin. Although evidence demonstrating the true benefits of taTME over laparoscopic TME (LapTME) is still insufficient, accumulating data have revealed that, as compared with LapTME, taTME is associated with shorter operative time and a lower conversion rate without jeopardizing other short-term outcomes. However, taTME is a technically demanding procedure with specific complications such as urethral injury, and so sufficient experience of LapTME and step-by-step acquisition of the skills needed for this procedure are requisite. The role of transanal endoscopic surgery is expected to change, along with the recent progress in the treatment of rectal cancer, such as robotic surgery and the watch-and-wait strategy. Optimization of treatment will be needed in the future in terms not only of oncological but also of functional outcomes.

Evaluation of vascular pain in patients with colorectal cancer receiving peripheral venous chemotherapy with or without oxaliplatin.

Oxaliplatin is a key chemotherapy drug in patients with colorectal cancer. Administration of oxaliplatin via a peripheral vein often causes vascular pain. However, no studies have evaluated vascular pain in patients with colorectal cancer in relation to peripheral venous administration of chemotherapy with or without oxaliplatin. We evaluated oxaliplatin-induced vascular pain using subjective and objective methods. We determined if oxaliplatin induced vascular pain in patients with colorectal cancer using a Visual Analog Scale (VAS) and a PainVision PS-2100 device. We compared VAS score between chemotherapy regimens with or without oxaliplatin, and between genders. We also examined the correlations of VAS score with pain intensity examined by the PainVision PS-2100, and with age and vessel diameter. A total of 98 patients with colorectal cancer were enrolled in this study, including 78 patients who received oxaliplatin via peripheral venous administration and 20 who received chemotherapy without oxaliplatin. The median VAS scores in patients with and without oxaliplatin were 36.5 (interquartile range 9.0-60.0) and 0 (0-4.0), respectively (P < 0.001), and the median pain intensities according to PainVision were 43.5 (14.3-98) and 36.5 (9.3-58.5), respectively (P < 0.001). There was a positive correlation between VAS and pain intensity (r = 0.584), but no correlation between VAS score and age (r = -0.174) or vessel diameter (r = -0.107). Peripheral venous administration of oxaliplatin induced vascular pain, measured both subjectively and objectively, in patients with colorectal cancer, regardless of vessel diameter.

Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel.

AIM: To investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto (DKT) associated with transient receptor potential ankyrin 1 (TRPA1) channels in intestinal myofibroblasts. METHODS: Inflammatory and fibrotic changes were detected in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) chronic colitis model of wild-type and TRPA1-knockout (TRPA1-KO) mice via pathological staining and immunoblotting analysis. Ca2+ imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast (InMyoFib) cell TRPA1 channel function. Pro-fibrotic factors and transforming growth factor (TGF)-ß1-associated signaling were tested in an InMyoFib cell line by qPCR and immunoblotting experiments. Samples from non-stenotic and stenotic regions of the intestines of patients with Crohn's disease (CD) were used for pathological analysis. RESULTS: Chronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice. A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO mice. The active ingredients of DKT, i.e., hydroxy α-sanshool and 6-shogaol, induced Ca2+ influxes in InMyoFib, and this was antagonized by co-treatment with a selective TRPA1 channel blocker, HC-030031. DKT counteracted TGF-ß1-induced expression of Type I collagen and α-smooth muscle actin (α-SMA), which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of myocardin. Importantly, 24-h incubation with a DKT active component Japanese Pepper increased the mRNA and protein expression levels of TRPA1 in InMyoFibs, which in turn negatively regulated collagen synthesis. In the stenotic regions of the intestines of CD patients, TRPA1 expression was significantly enhanced. CONCLUSION: The effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis, and benefit inflammatory bowel disease treatment.

Expansion of transplanted islets in mice by co-transplantation with adipose tissue-derived mesenchymal stem cells.

The shortage of donor islets is a significant obstacle for widespread clinical application of pancreatic islet transplantation. To investigate whether adipose tissue-derived mesenchymal stem cells (ADSCs) induce expansion of transplanted islets, we performed co-transplantation experiments in a mouse model. Streptozotosin (STZ)-induced diabetic mice transplanted with 50 syngeneic islets remained hyperglycemic. However, hyperglycemia was ameliorated gradually when 50 islets were co-transplanted with ADSCs but not separately grafted into the contralateral kidney. Insulin and proinsulin contents of 120-day grafts containing 50 islets co-transplanted with ADSCs were significantly increased compared with those of 50 isolated islets. The Ki67-positive ratios in islets of the naïve pancreas, at 30 and 120 days grafts were 0.23%, 2.12%, and 1.52%, respectively. Ki67-positive cells were predominantly Pdx1+ and insulin+ cells. These results demonstrate that co-transplantation with ADSCs induces proliferation of transplanted islets in mice, suggesting a potential solution for the low efficiency of islet transplantation.

Activation of Myofibroblast TRPA1 by Steroids and Pirfenidone Ameliorates Fibrosis in Experimental Crohn's Disease.

BACKGROUND & AIMS: The transient receptor potential ankyrin 1 (TRPA1) channel is highly expressed in the intestinal lamina propria, but its contribution to gut physiology/pathophysiology is unclear. Here, we evaluated the function of myofibroblast TRPA1 channels in intestinal remodeling. METHODS: An intestinal myofibroblast cell line (InMyoFibs) was stimulated by transforming growth factor-ß1 to induce in vitro fibrosis. Trpa1 knockout mice were generated using the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. A murine chronic colitis model was established by weekly intrarectal trinitrobenzene sulfonic acid (TNBS) administration. Samples from the intestines of Crohn's disease (CD) patients were used for pathologic staining and quantitative analyses. RESULTS: In InMyoFibs, TRPA1 showed the highest expression among TRP family members. In TNBS chronic colitis model mice, the extents of inflammation and fibrotic changes were more prominent in TRPA1-/- knockout than in wild-type mice. One-week enema administration of prednisolone suppressed fibrotic lesions in wild-type mice, but not in TRPA1 knockout mice. Steroids and pirfenidone induced Ca2+ influx in InMyoFibs, which was antagonized by the selective TRPA1 channel blocker HC-030031. Steroids and pirfenidone counteracted transforming growth factor-ß1-induced expression of heat shock protein 47, type 1 collagen, and α-smooth muscle actin, and reduced Smad-2 phosphorylation and myocardin expression in InMyoFibs. In stenotic intestinal regions of CD patients, TRPA1 expression was increased significantly. TRPA1/heat shock protein 47 double-positive cells accumulated in the stenotic intestinal regions of both CD patients and TNBS-treated mice. CONCLUSIONS: TRPA1, in addition to its anti-inflammatory actions, may protect against intestinal fibrosis, thus being a novel therapeutic target for highly incurable inflammatory/fibrotic disorders.

Hepatectomy for Liver Metastases of Colorectal Cancer After Adoptive Chemoimmunotherapy Using Activated αß T-cells.

BACKGROUND/AIM: Various types of chemoimmunotherapies for malignant tumors have been reported. However, there are few reports on hepatectomy after chemoimmunotherapy. We evaluated the safety and efficacy of hepatectomy for patients with stage IV colorectal liver metastases (CLM) after chemoimmunotherapy using activated αß T-cells. PATIENTS AND METHODS: From June 2012 to December 2016, five patients who underwent hepatectomy after receiving capecitabine and oxaliplatin (XELOX) plus bevacizumab and ex vivo-expanded αß T-lymphocytes as first-line chemoimmunotherapy were included. RESULTS: The median age of the five patients (two men, three women) was 61.4 (range=56-75) years. The surgical procedure was partial hepatectomy in two, laparoscopic partial hepatectomy in two, and one case of partial hepatectomy with subsegmentectomy. There was no postoperative complication of Clavien-Dindo grade 3A or higher. One patient had multiple lung metastases. CONCLUSION: Hepatectomy after chemoimmunotherapy using activated αß T-cells for CLM can be performed safely.

Clinical Study on the Medical Value of Combination Therapy Involving Adoptive Immunotherapy and Chemotherapy for Stage IV Colorectal Cancer (COMVI Study).

BACKGROUND: Adoptive immunotherapy for cancer has evolved through development of novel technologies for generating a large number of activated killer cells, such as αß T-cells, γδ T-cells, and natural killer cells. There has been no prospective trial of combination therapy involving adoptive immunotherapy and first-line chemotherapy for stage IV colorectal cancer. The present pilot study aimed to evaluate the safety and feasibility of combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer (COMVI study). PATIENTS AND METHODS: The COMVI study was a prospective, single-arm pilot trial. Therapy in each 21-day treatment cycle involved XELOX (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1-14), bevacizumab (7.5 mg/kg on day 1), and αß T-lymphocytes (over 5×109 on day 18) cultured ex vivo with an immobilized antibody to CD3 and interleukin-2. RESULTS: The study included six patients (two men and four women) between June 2013 and September 2014. The median patient age was 68 years (range=55-75 years). The overall response rate was 83.3% [complete response in two (33.3%); partial response in three (50.0%); stable disease in one (16.7%); no cases of progressive disease]. The tumor volume reduction rate was 53% (range=38.0-100%). The median progression-free and overall survival durations were 567 and 966 days, respectively. Most adverse events were mild-to-moderate in intensity, and no grade 4 adverse events occurred in the six patients. Only one patient experienced grade 3 hypertension and ileus. Immunotherapy-associated toxicity was minimal in this study. CONCLUSION: Combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer is feasible and safe. Phase II prospective studies are needed to confirm the safety and efficacy of such chemoimmunotherapy.

Difference in Neutropenia due to Administration Schedule of TAS-102.

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102.

Phase II study on early start of chemotherapy after excising primary colorectal cancer with distant metastases (Pearl Star 02).

Initiating chemotherapy usually requires a delay of more than 4 weeks after surgically resecting colorectal cancer. However, there is little evidence regarding the required delay interval. We have previously reported a pilot study to determine the safety and feasibility of early initiation of chemotherapy after resecting primary colorectal cancer with distant metastases. We aimed to determine the safety and efficacy of early initiation of chemotherapy after resecting colorectal cancer with distant metastases.This phase II study (trial number UMIN000006310) was a prospective, single-arm trial. A total of 20 patients (men, 15 and women, 5) were enrolled. They underwent XELOX therapy (130 mg/m2 oxaliplatin on day 1+1000 mg/m2 capecitabine twice daily on days 1-4) on postoperative day 7 and XELOX+bevacizumab (7.5 mg/kg bevacizumab on day 1) after the second chemotherapy cycle.Baseline characteristics included a median age of 64 (range, 43-72) years. Surgical procedures included right hemicolectomy in six patients, sigmoidectomy in three, anterior resection in five, and Hartmann procedure in six. All patients started chemotherapy on postoperative day 7. Median progression-free survival was 14.9 months; overall response rate was 80%. Disease control rate was 100%. Grade 3 or higher hemotoxicity and grade 3 or higher non-hematological toxicity was noted in 5.0% and 25.0% of patients, respectively. Postoperative complications were observed in two patients (superficial incisional surgical site infection and ileus).Early initiation of chemotherapy after surgery is feasible. These findings suggest future changes of the start time of chemotherapy after surgery.

Objective evaluation of oxaliplatin-induced vascular pain secondary to peripheral vein administration.

BACKGROUND: During oxaliplatin chemotherapy administration via a peripheral vein, vascular pain requires changing of the intravenous infusion route on occasion. Vascular pain induced by anticancer drugs reduces the rate of patient continuation and completion of chemotherapy. Pain is presently appraised using subjective methods, such as the visual analog scale (VAS). However, because pain evaluation can vary depending on the physical state and mood of the patient at the time of assessment, it is desirable to evaluate pain objectively. PainVision PS-2100 (PV) is a medical device that was designed to objectively and quantitatively assess patient nociception and perception. METHODS: The present study examined the correlation of subjective and objective assessment of oxaliplatin-induced vascular pain using VAS and PV, respectively. RESULTS: Vascular pain was assessed using both PV and VAS a total of 173 times for 58 colorectal cancer patients. Partial correlation analysis was performed to evaluate the relationship between PV and VAS. The mean PV and VAS scores were 44.5 (range: 0-596) and 24.8 (range: 0-100), respectively. The partial correlation coefficient was 0.408 (p < 0.0001). CONCLUSIONS: A strong correlation was not observed between the results, and a weak correlation was observed between VAS and PV scores. Objective evaluation of oxaliplatin-induced vascular pain will be required to help patients overcome vascular pain.

5-Fluorouracil Chemotherapy for Dihydropyrimidine Dehydrogenase-deficient Patients: Potential of the Dose-escalation Method.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) degrades approximately 85% of administered 5-fluorouracil (5-FU). With a reported high mortality rate, chemotherapy is generally contraindicated for patients with DPD deficiency. PATIENTS AND METHODS: Chemotherapy was initiated for a 73-year-old man with DPD deficiency. Capecitabine was administered in incrementally increasing doses, beginning with a single pill while monitoring plasma 5-FU concentration, and neutrophil and platelet counts. RESULTS: DPD protein level was 2.35 U/mg. After increasing the capecitabine dose to 1,800 mg, oxaliplatin and bevacizumab were added. Subsequent DPD protein measurement showed that the level had increased to approximately 12-fold the one before chemotherapy. Sequencing of all 23 exons of DPYD gene revealed a mutation of guanine to thymine in exon 11 (1156 G>T). CONCLUSION: This is the first report to indicate that DPD activity can be induced. These findings may provide early indications of a new method for chemotherapy for DPD-deficient patients.

HMGB1-Mediated Early Loss of Transplanted Islets Is Prevented by Anti-IL-6R Antibody in Mice.

OBJECTIVES: The limited success in achieving insulin independence of patients with type 1 diabetes mellitus after islet transplantation from a single donor, mainly due to early loss of transplanted islets, hampers clinical application of islet transplantation. Previously, we have shown in mice that the early loss of transplanted islets in the liver, the site of islet transplantation, is caused by innate immune rejection triggered by high-mobility group box 1 (HMGB1) protein released from transplanted islets. We herein determined whether the HMGB1-mediated early loss of transplanted mouse islets is prevented by anti-interleukin-6 receptor (IL-6R) antibody. METHODS: The effect of anti-IL-6R antibody on amelioration of hyperglycemia in streptozocin-induced diabetic mice receiving 200 islets into the liver from a single donor was evaluated in association with HMGB1-stimulated interferon-γ production of hepatic mononuclear cells. RESULTS: Hyperglycemia of diabetic mice receiving 200 syngeneic islets was ameliorated with down-regulation of interferon-γ production of hepatic natural killer T cells and neutrophils when anti-IL-6R was administered at the time of transplantation. This beneficial effect was also seen in allografts when alloimmune rejection was prevented by anti-CD4 antibody. CONCLUSIONS: These findings demonstrate that anti-IL-6R antibody prevented the early loss of intrahepatic islet grafts with inhibiting HMGB1-induced immune activation after islet transplantation.

Can grade 2 neutropenia predict the risk of grade 3 neutropenia in metastatic colorectal cancer patients treated with chemotherapy?

PURPOSE: Neutropenia is a major factor affecting continuation of chemotherapy for colorectal cancer. In many clinical trials, a neutrophil count of >1500 is targeted for continuation; for a count of <1500, medication is commonly discontinued. However, there is no definitive evidence supporting the need for a neutrophil count of 1500 for continuation of chemotherapy. In the clinical trials that we conducted, we discontinued chemotherapy when the neutrophil count was <1000 (grade 3); for a count of 1000-1500 (grade 2), chemotherapy was continued. Therefore, even practical treatment uses the same setting. Our aim was to examine neutrophil counts during continuation of chemotherapy in colorectal cancer patients with counts of 1000-1500 and to assess the need for discontinuation of medication for neutrophil counts in this range. Moreover, we examined neutrophil counts during the previous course of chemotherapy when they fell below 1000. METHODS: The study included 144 patients who received XELOX + bevacizumab therapy and XELOX therapy for advanced or recurrent colorectal cancer. RESULTS: Thirty (20.8 %) patients had neutrophil counts of 1000-1500. One (3.3 %) of 30 patients had a neutrophil count of <1000 during the following course of chemotherapy. Moreover, among the patients with neutrophil counts of <1000, 27.3 % had counts of 1000-1500 during the previous course of chemotherapy and 72.7 % had counts of >1500. CONCLUSIONS: Based on these results, grade 2 neutropenia cannot predict the risk of grade 3 neutropenia. Continuation of chemotherapy in patients with neutrophil counts of 1000-1500 may be appropriate, and discontinuation of therapy is not always required.