Identification of heparin-binding proteins expressed on Trichosporon asahii cell surface.

Trichosporon asahii is a pathogenic yeast that cause trichosporonosis. T. asahii exhibits several colony morphologies, such as white (W)- or off-white (O)-type, which may affect virulence. In this study, we compared the expression pattern of heparin-binding proteins in various colony morphologies and identified heparin-binding protein in T. asahii. Surface plasmon resonance analysis revealed that cell surface molecules attached more strongly to heparin in W- than O-type cells. We purified and identified a heparin-binding protein strongly expressed in W-type cells using heparin-Sepharose beads, named it heparin-binding protein 1 (HepBP1), and expressed Flag-tagged HepBP1 in mammalian cells. The heparin-binding ability of Flag-tagged HepBP1 was confirmed by pulldown assay using heparin-Sepharose beads. Thus, HepBP1 is a heparin-binding protein on T. asahii cell surface. These results suggest that several T. asahii cell surface proteins interact with glycosaminoglycans; therefore, they could contribute to infection.

Sentinel Node Navigation Surgery for Early Gastric Cancer: Analysis of Factors Which Affect Direction of Lymphatic Drainage.

BACKGROUND AND PURPOSE: We started performing sentinel node navigation surgery (SNNS) for patients with early gastric cancer (EGC) using infrared ray electronic endoscopy (IREE) with indocyanine green injection from year 2000. The EGCs usually have complex lymphatic drainage, unidirectional or multidirectional lymphatic flow. In this study, we investigated and clarified factors that affect the direction of gastric lymphatic drainage. PATIENTS AND METHOD: Consecutive 60 patients with EGC who underwent SNNS by IREE from year 2006 to 2014 were enrolled to this study. Patients' age, gender, location of tumors, operative method, previous treatment by endoscopic submucosal dissection (ESD), presence of pathological ulcerative scar and maximum tumor diameter were enrolled as parameters which may affect direction of lymphatic drainage and analyzed. RESULT: Bivariate analysis demonstrated that the presence of pathological ulcerative scar (P = 0.01), tumor location (g.c vs. a.w vs. p.w vs. l.c, P = 0.01), and maxim tumor diameter (P = 0.0003) were relevant to direction of gastric lymphatic drainage. Multivariate analysis showed that tumor location (g.c/a.w/p.w vs. l.c, odds ratio 8.227, P = 0.011) and the maximum tumor diameter (odds ratio 1.057, P = 0.037) are independent factors that affect direction of gastric lymphatic flow. Of tumors, 78% located at lesser curvature had unidirectional lymphatic drainage, and 93% of tumors whose diameter was 40 mm and more had multidirectional lymphatic drainage. CONCLUSION: Our investigation revealed that the tumor location and tumor diameter were the key factors which affect the direction of lymphatic drainage, which is useful fact to understand the complexity of gastric lymphatic drainage.

Short-term surgical outcomes of reduced port surgery for esophageal achalasia.

PURPOSE: To clarify the feasibility and utility of reduced port surgery (RPS) for achalasia. METHODS: Between September 2005 and June 2013, 359 patients with esophageal achalasia, excluding cases of reoperation, underwent laparoscopic Heller myotomy and Dor fundoplication (LHD) according to our clinical pathway. Three-hundred and twenty-seven patients underwent LHD with five incisions (conventional approach), while the other 32 patients underwent RPS, including eight via SILS. The clinical data were collected in a prospective fashion and retrospectively reviewed. We selected 24 patients matched for gender, age and morphologic type with patients in the RPS group from among the 327 patients (C group). The surgical outcomes were compared between the C and RPS groups. RESULTS: There were no significant differences between the two groups in the duration of symptoms, dysphagia score, chest pain score, shape of the distal esophagus and esophageal clearance. The operative time was significantly longer in the RPS group than in the C group (p < 0.001). There were no significant differences between the two groups in the length of postoperative hospital stay or rates of bleeding, mucosal injury of the esophagus and/or stomach and postoperative complications. The symptom scores significantly improved after surgery in both groups (p < 0.001). Furthermore, there were no significant differences between the C group and RPS group in terms of the postoperative symptom scores or satisfaction scores after surgery. CONCLUSIONS: The surgical outcomes of RPS for achalasia are comparable to those obtained with the conventional method.

Interaction of Host Proteins with Cell Surface Molecules of the Pathogenic Yeast Trichosporon asahii.

Trichosporon asahii is an invasive pathogenic yeast that infects immunocompromised hosts. Several virulence factors contribute to the fungal infection; however, the factors that contribute to the occurrence of T. asahii infections remain unclear. Since adhesins are typical virulence factors reported for pathogenic fungi, we looked for host proteins that interact with the T. asahii cell surface. T. asahii and Candida albicans were used for screening using a pull-down assay with fetal bovine serum. Serum albumin and elongation factor 2 were identified as the yeast-binding serum proteins. Additionally, we investigated the interactions of the cell surface-associated molecules (CSM) of T. asahii with vitronectin (VTN), fibronectin, fetuin-A, and alpha-1antitrypsin (AAT). The surface plasmon resonance (SPR) method was used to examine the interaction between CSM and human proteins. On the other hand, the pull-down assay was used to examine the interaction between human proteins and the T. asahii cell surface. Serum albumin, AAT, and VTN were found to interact with T. asahii in both SPR and pull-down assays. This study identified several proteins that interact with T. asahii, suggesting that these proteins play a role in infection mechanisms.

Effect of laparoscopic esophagomyotomy on chest pain associated with achalasia and prediction of therapeutic outcomes.

BACKGROUND: The effect of myotomy for achalasia on chest pain has not been clarified. The current study aimed to investigate the therapeutic effect of laparoscopic myotomy on chest pain associated with achalasia and to identify prognostic factors for outcomes. METHOD: Between March 2005 and September 2008, 95 patients were available for detailed interviews and for assessment of clearance by timed barium esophagogram (TBE) before and after surgery. Of the 95 patients, 47 (24 men; mean age, 42.9 ± 13.5 years) who experienced chest pain before surgery were studied. The subjects were asked in detail about dysphagia and chest pain before surgery and 6 months after surgery. The frequency and severity of the symptoms were graded on a scale of 0 to 4. In addition, the values obtained by multiplying the grade for frequency by the grades for severity of the two symptoms were defined as the dysphagia score and the chest pain score, respectively. The patients with chest pain scores of 0 after surgery were defined as group A and those with scores smaller than their preoperative scores as group B. The remaining patients with other scores were defined as group C. The background factors and clinical conditions of the three groups were compared. RESULTS: The mean chest pain score decreased from 5.0 ± 3.2 to 1.0 ± 1.6 (p < 0.001). The score after surgery was 0 for 27 patients and showed a decrease for 15 patients. Although the three groups did not differ in their characteristics, differences were noted in postoperative TBE factors (i.e., groups A and B had significantly shorter barium columns than group C at 1 and 5 min after surgery (p = 0.001). CONCLUSION: Laparoscopic myotomy had a therapeutic effect on chest pain associated with achalasia, and improvement in postoperative esophageal clearance may influence the therapeutic effect.

A disposable, ultra-fine endoscope for non-invasive, close examination of the intraluminal surface of the peritoneal dialysis catheter and peritoneal cavity.

The ability to visualize intraluminal surface of peritoneal dialysis (PD) catheter and peritoneal cavity could allow elucidation of the cases of outflow problems, and provide information on changes to the peritoneal membrane leading to encapsulating peritoneal sclerosis. A non-invasive examination that allows those monitoring in need is desirable. We have developed a disposable ultra-fine endoscope that can be inserted into the lumen of the existing PD catheter, allowing observation of the luminal side of the catheter and peritoneal cavity from the tip of the PD catheter, with minimum invasion in practice. In a pre-clinical study in pigs and a clinical study in 10 PD patients, the device provided detailed images, enabling safe, easy observation of the intraluminal side of the entire catheter, and of the morphology and status of the peritoneal surface in the abdominal cavity under dwelling PD solution. Since this device can be used repeatedly during PD therapy, clinical application of this device could contribute to improved management of clinical issues in current PD therapy, positioning PD as a safer, more reliable treatment modality for end-stage renal disease.

Efficacy of Percutaneous Endoscopic Gastrostomy for Patients With Esophageal Cancer During Preoperative Therapy.

BACKGROUND/AIM: This study aimed to clarify the benefits and disadvantages of percutaneous endoscopic gastrostomy (PEG) for patients with esophageal cancer (EC) during preoperative therapy. MATERIALS AND METHODS: We retrospectively reviewed 92 patients who underwent esophagectomy for EC after preoperative therapy. Patients were divided into the PEG group (n=14) and the control group (n=78) and compared regarding patient characteristics, nutritional status, operative variables, and postoperative complications. RESULTS: In the PEG group first nutritional status and tumor stage were significantly worse, but changes of nutritional status from first visit to operation were significantly better. According to the intraoperative thermal imaging, there was no patient with blood flow disturbance in the gastric conduit due to PEG. Short-term surgical outcomes did not significantly differ. CONCLUSION: PEG has less adverse effects on gastric tube production in esophagectomy and may be considered in highly selective patients during preoperative therapy.

Candida albicans abrogates the expression of interferon-gamma-inducible protein-10 in human keratinocytes.

Candida albicans is the predominant causative agent of human cutaneous candidiasis. Epidermal keratinocytes play an important role in the cutaneous immune response through the production of cytokines and chemokines, including IFN-gamma-inducible protein 10 (IP-10). Here, we investigated the influence of C. albicans infection on IP-10 production by normal human epidermal keratinocytes (NHEK) in vitro. Our results showed that IFN-gamma-stimulated NHEK showed enhanced IP-10 mRNA and protein expression; this expression was downregulated by C. albicans infection. Candida tropicalis also impaired IFN-gamma-induced IP-10 expression, but Candida glabrata did not. Heat-killed C. albicans did not impair IFN-gamma-induced IP-10 expression. We found that coincubation of NHEK with live C. albicans without cell-to-fungi contact impaired IFN-gamma-induced IP-10 mRNA and protein expression in NHEK, suggesting the role of soluble factors derived from live C. albicans in this impairment. Enzyme-linked immunosorbent assay analysis revealed that C. albicans and C. tropicalis could produce marked levels of prostaglandin (PG) E(2), while C. glabrata produced low levels of this prostaglandin. Treatment with E-series prostaglandin receptor antagonists, AH6809 and AH23848, restored IFN-gamma-induced IP-10 expression in C. albicans-infected NHEK. Thus, Candida-derived PGE(2) may impair IFN-gamma-induced IP-10 expression in human keratinocytes and may play a role in the pathogenesis of cutaneous candidiasis.

Frequent splicing aberration of the base excision repair gene hMYH in human gastric cancer.

BACKGROUND: Missense mutation of hMYH, which prevents transversion mutations induced by oxidative DNA damage, is reportedly associated with the development of gastric and colon cancer. We investigated whether deficiency or mutation of hMYH is associated with gastric carcinogenesis. PATIENTS AND METHODS: Thirty patients with gastric carcinoma, three gastric cancer cell lines and lymphocytes from three healthy volunteers were investigated. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for hMYH, and the full-length sequence of hMYH mRNA was analysed. RESULTS: A silent mutation at codon 473 was seen in two tumours. Single nucleotide polymorphism at codon 345 was observed in 14 patients. These two base substitutions had no pathogenic effect. Seven splice variants were observed and two aberrant transcripts were detected more frequently in cancer specimens (67%) than in normal mucosa (10%). CONCLUSION: The high frequency of splicing aberration in cancer tissues suggests that aberrant transcripts may be involved in gastric carcinogenesis and cancer development.

Epidural administration of morphine facilitates time of appearance of first gastric interdigestive migrating complex in dogs with paralytic ileus after open abdominal surgery.

Morphine is known to delay gastric emptying and intestinal transit, although epidural morphine is believed to decrease postoperative complications. However, these findings are still controversial and based only on clinical observations. We investigated the effects of epidural morphine administration on gut motility by measuring interdigestive migrating complex after open surgery in dogs. Twenty-eight beagles were divided into four groups (n = 7 each) to receive epidural saline (control group), epidural morphine, epidural ropivacaine, or low-dose continuous intravenous morphine. Strain gauge force transducers were sutured under open operation to the serosal surface of the stomach, duodenum, jejunum, and ileum to monitor gut motility. Time of appearance of first interdigestive migrating complex from the stomach propagated to the distal intestine was significantly shorter in the group that received epidural morphine compared with the other three groups. These results suggest that epidural administration of morphine may facilitate recovery from paralytic ileus after open abdominal surgery, perhaps through its effects on the central nervous system.

Association of extracellular matrix metalloproteinase inducer in endometrial carcinoma with patient outcomes and clinicopathogenesis using monoclonal antibody 12C3.

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMPs). We evaluated whether EMMPRIN expression is related to tumor progression and patient outcome in human endometrial carcinoma. Paraffin-embedded surgical tissue samples from 112 patients with endometrial carcinoma were stained with anti-EMMPRIN antibody (monoclonal antibody 12C3:MoAb 12C3) for immunohistochemical analysis. EMMPRIN protein was expressed in cancerous lesions with the incidence of 97.3% (109 of 112 cases), but not in normal lesions. The scores determined by the combination of intensity and pattern of EMMPRIN staining in cancer cells correlated significantly with various histopathological risk factors: advanced stage, P=0.001; poorly differentiated carcinoma, P<0.001; lymph node metastasis, P=0.002; and lymphatic vessel infiltration, P=0.027. More importantly, recurrence-free survival was shortened in patients with higher EMMPRIN scores (HR, 3.08; 95% CI, 1.32-7.19; P=0.01). These results suggest that measurement of EMMPRIN expression with simple immunohistochemical staining may enhance the understanding of the pathophysiology of endometrial carcinoma.

Gastric ulcer after laparoscopic fundoplication for gastroesophageal reflux disease: significance of the eradication of Helicobacter pylori.

The occurrence of gastric ulcers after laparoscopic fundoplication for gastroesophageal reflux disease is not uncommon. Between December 1994 and December 2004, we performed laparoscopic fundoplication in 180 patients, of whom 4 (2.2%) men developed a gastric ulcer during follow-up. The ulcers occurred predominantly in the upper part of the lesser curvature of the stomach, which is definitely different from the usual location of gastric peptic ulcers. All cases we experienced had Helicobacter pylori infection and eradication was attempted in all of them. Although eradication was not possible in 1 patient because of adverse effects to the drugs, successful eradication was obtained in the remaining 3 patients. After successful eradication, these 3 patients were placed under observation without medication and the ulcer has not recurred. The eradication of H. pylori may be an effective therapeutic means to prevent gastric ulcers recurrence after fundoplication.

Cytokine secretion profiles of human keratinocytes during Trichophyton tonsurans and Arthroderma benhamiae infections.

Dermatophytes cause intractable superficial infections in humans. Arthroderma benhamiae, a zoophilic dermatophyte, triggers severe inflammatory responses in humans, while Trichophyton tonsurans, an anthropophilic dermatophyte, triggers minimal ones. Cytokines and other factors derived from keratinocytes play important roles in inflammatory and immune responses in the skin. The authors performed an in vitro investigation to determine the human keratinocyte cytokine profiles during dermatophyte infection. The human keratinocyte cell line PHK16-0b was infected with A. benhamiae or T. tonsurans for 24 h, and the cytokines secreted were analysed using a human cytokine antibody array. Marked differences were observed in the cytokine profiles of the cells infected with the two dermatophytes. A. benhamiae infection resulted in the secretion of a broad spectrum of cytokines, including proinflammatory cytokines, chemokines, and immunomodulatory cytokines. In contrast, T. tonsurans-infected keratinocytes secreted only limited cytokines, including eotaxin-2, interleukin (IL)-8 and IL-16. cDNA microarray analysis confirmed that A. benhamiae infection upregulated genes encoding IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-13, IL-15, IL-16, IL-17 and interferon (IFN)-gamma, while T. tonsurans infection upregulated only a few genes, such as those encoding IL-1beta and IL-16. RT-PCR demonstrated that infection by both dermatophytes enhanced IL-8 mRNA expression in keratinocytes. These results suggest that A. benhamiae-induced secretion of several cytokines from keratinocytes may be involved in a severe inflammatory response, and that the limited cytokine secretion from keratinocytes in response to T. tonsurans infection may result in a minimal inflammatory response in the skin. These cytokine profiles may aid in proving the clinical features of dermatophytosis.

Cytokine secretion profile of human keratinocytes exposed to Malassezia yeasts.

The lipophilic yeast Malassezia is an exacerbating factor in atopic dermatitis (AD). Among organisms of the Malassezia species, Malassezia globosa and Malassezia restricta are particularly dominant on the skin of AD patients. However, the precise role of Malassezia yeasts in the pathophysiology of AD remains uncertain. Keratinocytes play a critical role in cutaneous inflammatory and immune responses by secreting cytokines. In this study, we attempted to determine the cytokine secretion profiles of human keratinocytes that were exposed to Malassezia yeasts. The human keratinocyte cell line PHK16-0b was cocultivated with M. globosa or M. restricta for 24 h, and the resulting cytokine secretion profile was analysed using a cytokine antibody array. The keratinocytes responded to the two Malassezia species with different Th2-type cytokine profiles, i.e. M. globosa induced IL-5, IL-10 and IL-13 secretion from the keratinocytes, whereas M. restricta induced IL-4 secretion. Similar results were obtained with primary normal human epidermal keratinocytes. cDNA microarray analysis confirmed that IL-5, IL-10, and IL-13 mRNAs were induced only by M. globosa, while IL-4 mRNA expression was induced only by M. restricta. These findings suggest that M. globosa and M. restricta play a synergistic role in triggering or exacerbating AD by stimulating the Th2 immune response.

Laparoscopic Collis gastroplasty and Nissen fundoplication for reflux esophagitis with shortened esophagus in Japanese patients.

BACKGROUND: There is an extremely small number of surgical cases of laparoscopic Collis gastroplasty and Nissen fundoplication (LCN procedure) in Japan, and it is a fact that the surgical results are not thoroughly examined. PURPOSE: To investigate the results of LCN procedure for shortened esophagus. PATIENTS AND METHODS: The subjects consisted of 11 patients who underwent LCN procedure for shortened esophagus and followed for at least 2 years after surgery. The group of subjects consisted of 3 men and 8 women with an average age of 65.0+/-11.6 years, and an average follow-up period of 40.7+/-14.4 months. Esophagography, pH monitoring, and endoscopy were performed to assess preoperative conditions. Symptoms were clarified into 5 grades between 0 and 4 points, whereas patient satisfaction was assessed in 4 grades. The use of postoperative acid-reducing medication and the recurrence of esophagitis were also investigated. RESULTS: None of the patients experienced intraoperative complications, received transfusions, required conversion to open surgery, or died postoperatively. The average preoperative heartburn, regurgitation, and dysphagia scores were 2.36+/-1.29, 2.27+/-1.19, and 1.82+/-1.78 points, respectively. These scores improved after surgery to 0.55+/-1.21 (P=0.0063), 0.55+/-1.21 (P=0.0094), and 1.0+/-1.18 (P=0.1236) points, respectively. All patients had esophagitis preoperatively, which recurred in 3 patients (27%). In these 3 patients, acid-secreting mucosa was confirmed on the oral side of the wrap, by positive Congo-red staining. Hiatal hernia recurred in one patient, who also experienced recurrent esophagitis. Five patients received acid-reducing medication postoperatively. The degree of satisfaction was excellent in 2, good in 6 patients, fair in 2, and poor in 1 patient(s). CONCLUSIONS: Although the LCN procedure can be performed safely, the outcome was not necessarily satisfactory. The LCN procedure requires avoidance of residual acid-secreting mucosa on the oral side of the wrapped neoesophagus. If acid-secreting mucosa remains, continuous acid suppression therapy should be employed postoperatively.

Profiling gene expression ratios of paired cancerous and normal tissue predicts relapse of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma has heterogeneous clinical outcomes that cannot be predicted well using any existing clinical or molecular prognostic factors. Gene expression profiling may enable more precise prediction of the clinical outcome of these patients. We developed a new approach using gene expression ratios of paired cancerous and normal tissue specimens from the same patient to reduce the effects of variation among individuals. Using oligonucleotide microarrays, we analyzed total RNA expression levels corresponding to 12,600 transcript sequences in 24 paired cancerous and normal tissue operative specimens from 12 patients with esophageal squamous cell carcinoma. Hierarchical clustering analysis using gene expression ratios (cancer:normal) divided the 12 patients into two groups; all 7 patients in the first cluster survived without relapse (median follow-up, 483 days), whereas all 5 patients in the second cluster relapsed (median relapse-free survival time, 280 days; log-rank test, P = 0.006). In contrast, clustering either with cancerous tissue alone or with normal tissue alone did not show significant differences in the outcomes. The expressions of a variety of genes related with cell cycle, gene-repair, apoptosis and chemoradiotherpay resistance were up-regulated in the poor prognostic cluster. These results suggest that ratios of paired gene expression profiles may more efficiently predict relapse-free survival of esophageal squamous cell carcinoma than existing prognostic factors or than gene expression profiling with cancerous tissue alone.

Comparative Analysis of Extracellular Polymeric Substances from Cryptococcus gattii VGIIa Strain Isolated for the First Time in Japan.

Cryptococcus gattii and C. neoformans are pathogenic yeasts that cause meningoencephalitis. C. gattii has four molecular types: VGI, VGII, VGIII, and VGIV. Furthermore, three genotypes have been reported for VGII, and a high pathogenicity of the VGIIa genotype has been proposed. The VGIIa strain has been isolated from a patient in Japan, but little is known about the characteristics of the polysaccharides in this strain. In this study we examined the induction of interleukin-8（IL-8）transcriptional activation and compared the nuclear magnetic resonance（NMR）spectra of extracellular polymeric substances（EPSs）, mainly polysaccharides, from the VGIIa, VGIIb, and VGIIc genotypes. The induction of IL-8 by C. gattii EPSs was weaker than that by C. neoformans EPSs. The anomeric proton signals in the NMR spectra of EPSs obtained from VGII isolates were similar, and the polysaccharides were mainly mannose, xylose, galactose, and glucuronic acid. These results suggest that the extracellular polysaccharides from the VGIIa strain isolated in Japan are almost the same as those from other VGII strains.

Comparison of Short-term and Long-term Clinical Outcomes Between Laparoscopic and Open Total Gastrectomy for Patients With Gastric Cancer.

BACKGROUND AND PURPOSE: Validation of laparoscopic total gastrectomy (LTG) for patients with gastric cancer has not been fully investigated. In particular, the technique for esophagojejunostomy remains controversial. We performed 103 cases of LTG for patients with gastric cancer between 2007 and 2013, in which all esophagojejunostomy reconstruction was performed with intracorporeal circular stapling esophagojejunostomy using the OrVil system except for the first 3 cases. The purpose of this study is to retrospectively analyze the clinical usefulness of LTG with intracorporeal circular stapling esophagojejunostomy using the OrVil system and oncological feasibility of LTG as compared with open total gastrectomy (OTG). PATIENTS AND METHOD: We retrospectively analyzed clinical course of consecutive 100 operations with LTG in comparison with consecutive 53 operations with OTG for patients with gastric cancer. As an estimation of short-term outcome, operative time, blood loss, postoperative hospital days and postoperative data of blood and drain examination were included. Moreover, relapse-free survival time and overall survival time stratified by each stage were calculated by log-rank test as an estimation of prognostic relevance. RESULTS: Blood loss and postoperative hospital stay of LTG were significantly less than that of OTG. Postoperative complications were equivalent between the 2 groups and no patient died within 1 month post-LTG. Only 1 patient had recurrence and died for carcinomatosa peritonitis 50 months after LTG (median follow-up period: 44 mo). CONCLUSIONS: Our experience revealed that LTG with intracorporeal circular stapling esophagojejunostomy using the OrVil system could be performed safely and with acceptable oncological outcome for patients with gastric cancer.

Early Response of Esophageal Cancer to Neoadjuvant Chemotherapy with Docetaxel-Cisplatin-5-Fluorouracil Represents Sensitivity: A Phase II Study.

AIM: The aim of this study was to assess the response rate and find improvements. PATIENTS AND METHODS: Fifty-five patients with esophageal cancer were enrolled. Neoadjuvant chemotherapy (one or two courses) consisted of 60 mg/m(2)docetaxel on day 1, 70 mg/m(2)cisplatin on day 1 and continuous infusion of 5-fluorouracil at 600 mg/m(2)/day on day 1-5. All patients were examined for clinical response by computed tomography and endoscopy at each course. RESULTS: Grade 3/4 hematological toxicity was observed in 63.6% and grade 3/4 non-hematological toxicity in 41.8% of patients. The clinical response rate was 71% and histological complete response rate was 7.8%. We divided patients into three groups by clinical response to the first course of chemotherapy: partial response (PR), incomplete response (IR) and stable disease (SD). The final clinical response rate in those with SD to the first course was significantly lower (vs. those with PR p<0.001, vs. IR p<0.001). CONCLUSION: A high response rate was obtained and tolerability was good. Moreover, the presence of sensitivity to therapy was reflected in the initial clinical response.