The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial.

BACKGROUND: Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS: Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS: We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS: TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival. RESULTS: IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively). CONCLUSIONS: CXCR4 expression is associated with poor prognosis in patients with ESCC.

Aldehyde dehydrogenase 1 expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma.

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) and CD44 act as important biomarkers in several solid tumors. However, few studies have examined the relationships between ALDH1 expression and the prognosis and clinical characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: This study was a retrospective case-control study and included 152 patients with ESCC. A total of 56 patients underwent surgery (OP group), 40 patients received neoadjuvant chemotherapy involving weekly docetaxel plus 5-fluorouracil and low-dose cisplatin (DFP therapy) prior to undergoing surgery (NAC group), and 56 patients received initial systemic DFP therapy (CT group). The ALDH1 and CD44 immunohistochemical expression levels of each tumor were evaluated and compared with the prognosis and clinical characteristics of the ESCC patients. RESULTS: In the OP and NAC groups, multivariate analysis found that ALDH1 was independently associated with postoperative recurrence and prognosis (OP group, P=0.004 and 0.016, respectively; NAC group, P=0.026 and 0.014, respectively). In addition, CD44 was found to be associated with postoperative recurrence in the OP group and prognosis in the NAC group (P=0.024 and 0.047, respectively). Among the ALDH1-negative clinical stage II/III patients, the OP and NAC groups displayed better prognoses than the CT group (P<0.001). However, among the ALDH1-positive clinical stage II/III patients, the OP and NAC groups displayed poorer prognoses than the CT group (P=0.049). CONCLUSIONS: ALDH1 was found to be a predictor of postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of recurrence and prognosis. ALDH1 expression might affect the treatment strategy for ESCC.

[Pathological complete response in a case of advanced esophageal cancer invading aorta treated by preoperative chemotherapy with docetaxel and cisplatin plus 5-FU].

The patient was a 64-year-old man, diagnosed as cStage IVa esophageal cancer invading the aorta with lymph node metastasis. He received combination chemotherapy with docetaxel/cisplatin/5-FU(DFP therapy). After one course, CT and endoscopic examination showed remarkable reduction of the primary lesion and lymph node metastasis. We performed subtotal esophagectomy and gastric tube reconstruction by the retroposterior mediastinum route. The pathological specimen evidenced fibrosis and infiltration of inflammatory cells on almost all layers, but showed no viable malignant cells in the middle thoracic esophagus. Therefore, the pathological effect was judged as Grade 3(pCR). This case suggested that DFP combination chemotherapy may prove to be a useful treatment for advanced esophageal cancer with invasion to other organs.

Prognosis of esophageal squamous cell carcinoma in patients positive for human epidermal growth factor receptor family can be improved by initial chemotherapy with docetaxel, fluorouracil, and cisplatin.

BACKGROUND: The human epidermal growth factor receptor (HER) family, Ki-67 and p53 are important biomarkers for several malignancies. However, few studies have examined the role of these in prognosis and therapeutic sensitivity of esophageal squamous cell carcinoma (ESCC). The efficacy of triple-drug combination therapy with docetaxel, fluorouracil and cisplatin has recently been expected for ESCC. METHODS: Subjects comprised 142 patients with ESCC who underwent operation (OP group, n = 54), neoadjuvant chemotherapy with docetaxel, fluorouracil, and cisplatin (DFP therapy) followed by operation (NAC group, n = 37) or initial systemic DFP therapy (CT group, n = 51) between January 2004 and December 2010. Immunohistochemical expressions of epidermal growth factor receptor (EGFR), HER2, HER3, Ki-67, and p53 were evaluated and compared with prognosis and sensitivity to DFP therapy. RESULTS: Positive correlations existed between EGFR, HER2, and HER3 expressions. In the OP group, EGFR was independently associated with postoperative recurrence in multivariate analysis (P = .036). In the NAC group, EGFR correlated with pathological response to DFP therapy (P = .004). In the CT group, EGFR, HER2, and HER3 correlated with clinical response to DFP therapy and EGFR was independently associated with favorable prognosis in multivariate analysis (P = .022). CONCLUSION: EGFR represents a predictor of postoperative recurrence and sensitivity to triple-drug combination therapy including a taxane. EGFR-positive patients may show improved prognosis with taxane combination chemotherapy and molecular targeted therapy for HER family members.

Sentinel lymph node biopsy using intraoperative indocyanine green fluorescence imaging navigated with preoperative CT lymphography for superficial esophageal cancer.

BACKGROUND: The sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer. METHODS: Subjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG. RESULTS: Lymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures. CONCLUSIONS: Preoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.

[A case of a patient with stage IVa esophageal cancer surviving over 4 years by combination chemotherapy with docetaxel,5 -FU and cisplatin, without operation].

A male patient in his 50s was found to have lower thoracic advanced esophageal squamous cell carcinoma by upper gastrointestinal endoscopy with the chief complaint of dysphagia in July 2006. CT revealed supraclavicular lymph node metastasis, and he was diagnosed as clinical stage IVa. He underwent two courses of combination chemotherapy with docetaxel, 5-FU and cisplatin(DFP therapy: docetaxel at 25mg/m / / 2 on day 1, 5-FU at 370 mg/m2 on days 1-5, and cisplatin at 7 mg/m2 on days 1-5 were repeated weekly for 4 weeks). The primary tumor disappeared and the lymph node was reduced as observed by upper gastrointestinal endoscopy and CT. After 2 courses of DFP therapy, PET-CT revealed that the primary tumor and lymph node had no new accumulation. Because he refused both operation and chemoradiotherapy, the patient underwent oral chemotherapy. In January 2010, PET-CT and upper gastrointestinal endoscopy revealed that the primary tumor relapsed. DFP therapy was performed and was effective once again. He has survived for over 4 years and 4 months without operation.

Gasless single-port laparoscopic cholecystectomy.

Purpose: Single-port laparoscopic surgery is anticipated to become the future of minimally invasive surgery. We have devised an alternative approach for laparoscopic cholecystectomy by inserting a single port at the umbilicus and using the abdominal wall-lifting method, without establishing pneumoperitoneum. Methods: Retrospective analysis of 130 patients undergoing laparoscopic cholecystectomy was done to compare the conventional laparoscopic cholecystectomy (CLC) (n = 69) and the novel single-port laparoscopic cholecystectomy (SLC) using the abdominal wall-lifting method (n = 61). The surgical procedures were as follows. A 2- to 3-cm transumbilical incision was made, and a wound retractor was inserted into the abdomen without difficulty. Abdominal distension was obtained using a fan-shaped retractor without the use of carbon dioxide insufflations. A 5-mm flexible scope and modified curved graspers and dissectors were used to give the feeling of triangulation during dissection. Results: The SLC group consisted of 25 males and 36 females with a mean age of 58.1 ± 7.2 years and a mean body mass index of 23.1 ± 3.2 kg/m2. The two groups were comparable for mean age, sex, disease, American Society of Anesthesiologists physical status classification, and comorbidity. Likewise, the duration of operation, postoperative hospital stays, complications, the number of use of analgesics, and conversion rate to open technique were not significantly different in the two groups. Conclusion: The impaired view in single-port laparoscopic surgery can be improved by using articulating instruments that can be rotated out of the field of view. This novel gasless method is cost-effective and produces minimal postoperative discomfort with no additional scars.

Phase 1 Dose-Escalation Study of Triweekly Nab-Paclitaxel Combined With S-1 for HER2-Negative Metastatic Breast Cancer.

PURPOSE: To evaluate the efficacy, toxicity, maximum tolerated dose, and recommended dose of triweekly nab-paclitaxel (nab-PTX) and S-1 combination chemotherapy for patients with metastatic breast cancer. PATIENTS AND METHODS: This phase 1 study was conducted with a standard 3 + 3 dose escalation design. Every 3 weeks, the patients received nab-PTX at 180-260 mg/m2 on day 1 and S-1 at 65-80 mg/m2 daily on days 1 to 14. RESULTS: Ten HER2-negative metastatic breast cancer patients were enrolled; their median number of prior chemotherapy regimens was 3. Dose-limiting toxicity was observed in the first patient assigned to level 4; grade 4 febrile neutropenia and grade 3 neurotoxicity such as needing a wheelchair occurred. Therefore, an additional patient was not assigned to level 4. The maximum tolerated dose was considered level 4 (260 mg/m2 nab-PTX with 80 mg/m2 S-1). The recommended dose determined was level 3 (220 mg/m2 nab-PTX with 80 mg/m2 S-1). The response rate was 60.0%. The disease control rate was 70.0%. CONCLUSION: This combination chemotherapy therapy was feasible and safe for patients with HER2-negative metastatic breast cancer.

Gene expression changes in a chemoresistant model with human esophageal cancer xenografts using cDNA microarray.

BACKGROUND: 5-Fluorouracil (5-FU) and cisplatin combined chemotherapy (FP) is commonly used for esophageal cancer. Acquired resistance needs to be overcome to improve the chemotherapeutic effect. MATERIALS AND METHODS: The FP-resistant xenograft model using severe combined immunodeficient (SCID) mice was established as an acquired resistance model. RNA was extracted pretreatment, at the onset of the anticancer effect, during the most effective, and regrowth period in the FP administration group and during the mid-progressive period and the far advanced period in the control group. A microarray was applied to explore gene expression changes. RESULTS: The data set containing up-regulated genes in the regrowth period was uploaded into Ingenuity Pathway Analysis. The expression change profiles suggested that activation of not only 5-FU- and cisplatin-specific genes, but also the Phosphoinositide 3-kinase (PI3K)/AKT signal were associated with FP resistance. CONCLUSION: A xenograft model using SCID mice with esophageal cancer cells would monitor gene changes during treatment and regrowth.

Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study).

BACKGROUND: To improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. PATIENTS AND METHODS: Patients were treated with docetaxel (40 mg/m2 intravenously on day 1) and S-1 (40 mg/m2 orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. RESULTS: Ninety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. CONCLUSION: The S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.

Preoperative diagnosis of sentinel lymph node (SLN) metastasis using 3D CT lymphography (CTLG).

BACKGROUND: Sentinel lymph node biopsy (SLNB) became a standard procedure for patients with early breast cancer, however, an indication of SLN navigation to metastatic disease may lead to misdiagnosis for staging. Preoperative CTLG with a water-soluble iodinated contrast medium visualizes the correct primary SLNs and its afferent lymphatic channels surrounding detailed anatomy, therefore it can predict LN metastasis by visualizing the lymph vessel obstruction or stain defect of the SLN by tumor. The current study presents the value of CTLG for preoperative prediction for SLN status. METHODS: A total of 228 patients with Tis-T2 breast cancer who did not receive primary chemotherapy were studied. SLN metastasis was diagnosed according to the following staining patterns of SLNs and afferent lymphatic vessels: stain defect of SLN, obstruction, stagnation, dilation, and detour of the lymphatic vessels by tumor occupation. The diagnosis was compared with the pathological results to evaluate the accuracy of prediction for SLN metastasis using CTLG. RESULTS: Twenty-seven of 228 patients had metastatic SLN pathologically. Twenty-five of these were diagnosed as metastatic preoperatively. The accuracy for metastatic diagnosis using CTLG was 89.0%, sensitivity was 92.6%, and specificity was 88.6%. The positive predictive value was 52.1% and negative predictive value was 98.8%. CONCLUSION: CTLG can select the candidate with truly node negative cases in early breast cancer patients, because it predicts lymph node metastasis preoperatively from natural status of the lymphographic image. It also might omit the SLN biopsy itself.

Triple assessment of sentinel lymph node metastasis in early breast cancer using preoperative CTLG, intraoperative fluorescence navigation and OSNA.

BACKGROUND: Sentinel lymph node biopsy (SLNB) became a standard surgical procedure for patients with early breast cancer; however, the optimal method of sentinel lymph node (SLN) identification remains controversial. The current study presents the protocol of our institution for preoperative and intraoperative SLN detection. METHODS: Fifty female patients with early breast cancer and clinically node-negative axilla were enrolled in this study. All patients underwent preoperative CT lymphography (CTLG), intraoperative SLNB using fluorescence navigation, intraoperative one-step nucleic acid amplification (OSNA) and postoperative hematoxylin and eosin histopathological analysis. Prediction of metastasis by CTLG and detection of metastasis by OSNA were compared to results of histopathology as standard reference. RESULTS: SLN were identified by preoperative CTLG and intraoperative SLNB with fluorescence navigation in all patients, the identification rate was 100 %. SLN metastases were detected as positive by OSNA in 9 patients (18 %), 4 were (++), 4 were (+) and 1 was (+I). SLN metastases were detected as positive by histopathology in 10 patients (20 %). The concordance rate between OSNA and permanent sections was 90 %. The negative predictive value of CTLG was 80 %. CONCLUSION: Use of CTLG and fluorescence navigation made performing SLNB with high accuracy possible in institutions that cannot use the radioisotope method. OSNA provided accurate intraoperative method, allowing for completion of axillary node dissection during surgery and avoidance of second surgical procedure in patients with positive SLNs, thereby reducing patient distress and, finally, saving hospital costs.

Immunocytochemical results for HER2 and Ki67 in breast cancer touch-smear cell specimens are reliable.

BACKGROUND: Re-evaluation of the subtype of recurrent breast cancer is necessary for deciding the treatment approach, but it is often not performed due to the difficulty of obtaining tissue specimens from a recurrent lesion, etc. However, when a recurrent lesion is close to the body surface, fine-needle aspiration cells (FNA cells) can be easily obtained, and immunocytochemical (ICC) analysis of hormone receptors expression in FNA cells is said to be highly reliable. However, there is no consensus regarding ICC analysis of human epidermal growth factor receptor type 2 (HER2) expression and the Ki67 index using FNA cells. METHODS: Touch-smear cells (TSC) were prepared from resected specimens from 36 patients with primary invasive ductal carcinoma of the breast. The TSC were fixed in 95 % ethanol and subjected to ICC analysis for HER2 using HercepTest™ (Dako) and Ki67 using MIB-1™ (Dako). HER2 expression and the Ki67 index for the TSC were compared with the results of immunohistochemical analysis of histological section (HS). Statistical analyses used the kappa test and Pearson's correlation coefficients. RESULTS: HER2 and Ki67 were analyzed in TSC from 36 and 28 patients, respectively. The HER2 expression scores in the TSC and HS groups showed good agreement (kappa value =0.640) and significant correlation (correlation coefficient =0.860, p < 0.001). The Ki67 indexes in the TSC and HS groups also showed significant correlation (correlation coefficient =0.861, p < 0.001). CONCLUSIONS: The reliability of ICC analysis of HER2 expression and the Ki67 index using TSC were recognized.

Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis.

Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.

Efficacy of percutaneous endoscopic gastrostomy on unplanned treatment interruption and nutritional status in patients undergoing chemoradiotherapy for advanced head and neck cancer.

OBJECTIVE: Efficacy of percutaneous endoscopic gastrostomy (PEG) on unplanned treatment interruption and nutritional status was examined in patients undergoing chemoradiotherapy (CRT) for advanced head and neck cancer. METHODS: We retrospectively reviewed hospital charts of 44 patients with advanced head and neck cancer who were treated with CRT. RESULTS: CRT-induced mucositis of grade 3 or worse and inadequate oral intake of less than one third of their usual intake developed in 33 patients who were recommended PEG placement, but not in 11 patients. Thirteen patients accepted PEG placement and then completed CRT (compliant group). However, among 20 patients who refused both PEG and nasogastoric tube (NGT) placements (non-compliant group), 10 required unplanned interruptions of CRT at a radiation dose around 30-40 Gy (UI-CRT group) while 10 others could complete CRT without interruption (C-CRT group) CRT. Total serum protein levels were significantly decreased after CRT in all patients. DISCUSSION: It is suggested that therapeutic PEG placement is useful for preventing unplanned interruption of CRT in patients with advanced head and neck cancer. After severe mucositis and inadequate oral intake have developed during CRT, PEG placement should be considered before the radiation therapy dose of 30 Gy.

Glutamine protects the small intestinal mucosa in anticancer drug-induced rat enteritis model.

Supportive therapy during chemotherapy has become essential, but effective preventive therapies to gastrointestinal mucosal injury are few. We investigated the efficacy of glutamine in rat anticancer drug-induced enteritis model. In this study, we used twenty male SD rats. They were divided into control, 5-fluorouracil (5-FU) (orally administered at 20 mg/kg day), 5-FU+glutamine (1000 mg/kg/day) and 5-FU+glutamine+fiber and oligosaccharide (GFO(®)) (1000 mg/kg/day) groups. All groups were sacrificed on day 6 and upper jejunums were excised. The jejunal villous height was measured in specimens. IgA level in jejunal washing solution, and serum diamine oxidase activity were also measured. The jejunal villous height was recognized as shorter in the specimen from 5-FU treated rats compared with 5-FU+glutamine treated rats (p<0.001). Serum diamine oxidase activity in 5-FU+glutamine group were significantly superior to that in 5-FU group (p=0.028). IgA level in jejunal washing solution tended to be higher in 5-FU+glutamine group than that in 5-FU group (p=0.076). On the other hand, serum diamine oxidase activity and IgA level in jejunal washing solution showed no significant difference between 5-FU+GFO and 5-FU treatment group. Our results suggest that glutamine showed protective effects on mucosal injury of small intestine in rat anticancer drug-induced enteritis model.