Publications (138)342.48 Total impact
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Article: Clinical significance of surgery for gastric submucosal tumours with size enlargement during watchful waiting period.
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ABSTRACT: BACKGROUND: The true impact of surgery for small, asymptomatic and biopsy-negative gastric submucosal tumours (SMTs) with size enlargement during 'watchful waiting' period has not been fully understood. METHODS: From 2005 to 2012, 100 patients with gastric SMTs underwent surgery. Twenty-three of them with size enlargement during observation period were enrolled in the retrospective analysis. Data included clinicopathologic findings, genetic findings, operative outcomes and prognoses. RESULTS: All patients (13 males, 10 females), with median age of 54 (41-71), had their lesions detected by routine health check-up (n=21) or incidentally (2). The tumours were 1.8 (0.5-4.0)cm in size at their initial detection, and enlarged up to 3.2 (2.0-7.0)cm at the operation during 63.0 (14.6-233.7) months. As surgical procedure, laparoscopic partial gastrectomy accounted for the majority (78.3%). Histologic examination revealed gastrointestinal stromal tumour (GIST) (21) and schwannoma (2). Although 16 out of 21 GISTs were categorised into 'Very low' (1), and 'Low' (13) risk according to Fletcher's classification, 'Intermediate' (5) and 'High' (2) risk were identified in the series. No recurrences/metastases were noted in 23.2 (0.9-87) months of postoperative follow-up. CONCLUSION: Our study revealed the existence of high mitotic GISTs in asymptomatic, small gastric SMTs with size enlargement, and laparoscopic surgery was safely applied to majority of those cases. Prompt surgical intervention should therefore be considered for those lesions.European journal of cancer (Oxford, England: 1990) 05/2013; · 4.12 Impact Factor -
Article: Preservation of the Celiac Branch of the Vagus Nerve during Laparoscopy-assisted Distal Gastrectomy: Impact on Postprandial Changes in Ghrelin Secretion.
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ABSTRACT: BACKGROUND: Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing properties. Because ghrelin is secreted mainly by the stomach, fasting levels fall after distal gastrectomy. The vagal nerve is responsible for periprandial changes. The presents study investigated the impact of preserving the celiac branch of the vagus nerve during laparoscopy-assisted distal gastrectomy on postoperative ghrelin secretion. METHOD: Between May 2009 and July 2010, 42 consecutive patients who underwent LADG were divided into two groups, the first in which the celiac branch of the vagus was preserved ("Preserved," n = 21) and the second in which it was not ("Not Preserved," n = 21). Blood samples were collected for assays of several hormones, including ghrelin, leptin, and insulin; these were taken before and 2 h after breakfast on postoperative day 7. RESULTS: There were no significant differences in the background characteristics of the two groups. Plasma fasting ghrelin decreased significantly after LADG, by about 50 % of the baseline values in both groups. Postprandial plasma ghrelin levels in the Preserved group were significantly lower than those in the Not Preserved group (23 ± 8 vs 32 ± 9 fmol/ml; p = 0.0058). The ratio of the total ghrelin concentration after breakfast to that before was defined as the A/B ratio. The mean preoperative and postoperative A/B ratios were almost the same in the Preserved group (preoperative vs postoperative: 0.41 vs 0.44; p = 0.52). On the other hand, the mean A/B ratio in the Not Preserved group increased from 0.41 to 0.61 postoperatively (preoperative vs postoperative; p = 0.0003). Preservation of the celiac branch of the vagus nerve during LADG was related to the prandial ghrelin changes.World Journal of Surgery 05/2013; · 2.36 Impact Factor -
Article: Aldehyde dehydrogenasehigh gastric cancer stem cells are resistant to chemotherapy.
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ABSTRACT: Cancer stem cells (CSCs) are known to influence chemoresistance, survival, relapse and metastasis. Aldehyde dehydrogenase (ALDH) functions as an epithelial CSC marker. In the present study, we investigated the involvement of ALDH in gastric CSC maintenance, chemoresistance and survival. Following screening for eight candidate markers (CD13, CD26, CD44, CD90, CD117, CD133, EpCAM and ALDH), five gastric cancer cell lines were found to contain small subpopulations of high ALDH activity (ALDHhigh cells). We also examined the involvement of ALDHhigh cell populations in human primary tumor samples. Immunodeficient NOD/SCID mice were inoculated with tumor tissues obtained from surgical specimens. ALDHhigh cells were found to persist in the xenotransplanted primary tumor samples. in the immunodeficient mice, ALDHhigh cells exhibited a greater sphere‑forming ability in vitro and tumorigenic potential in vivo, compared with subpopulations of low ALDH activity (ALDHlow cells). Cell cultures treated with 5-fluoro-uracil and cisplatin exhibited higher numbers of ALDHhigh cells. Notch1 and Sonic hedgehog (Shh) expression was also found to increase in ALDHhigh cells compared with ALDHlow cells. Therefore, it can be concluded that ALDH generates chemoresistance in gastric cancer cells through Notch1 and Shh signaling, suggesting novel treatment targets.International Journal of Oncology 04/2013; 42(4):1437-42. · 2.40 Impact Factor -
Article: C4.4A Expression Is Associated with a Poor Prognosis of Esophageal Squamous Cell Carcinoma.
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ABSTRACT: BACKGROUND: C4.4A is a glycolipid-anchored membrane protein expressed in several human malignancies. We examined clinical relevance of C4.4A expression in 111 esophageal squamous cell carcinoma (ESCC) tissue samples. METHODS: Anti-human C4.4A antibody that recognizes the glycosylphosphatidyl inositol (GPI) anchor signaling sequence (C4.4A-GPI Ab) and anti-human C4.4A-119 polyclonal antibody (C4.4A-119 Ab) were used for immunohistochemistry and Western blot testing. RESULTS: Both antibodies detected the C4.4A protein expression at the parabasal layer of normal epithelium of the esophagus. In tumor tissues, the C4.4A protein was detected in 66 (59.5 %) and 95 (85.6 %) of 111 ESCCs by the C4.4A-GPI Ab and the C4.4A-119 Ab, respectively. The C4.4A-GPI Ab mainly detected membranous C4.4A expression (83.3 %, 55 of 66 positive cases), while the C4.4A-119 Ab exclusively detected cytoplasmic C4.4A expression (100 %, 73 cytoplasm alone and 22 cytoplasm plus membrane in 95 positive cases). Western blot analysis indicated that normal epithelium expressed the band of C4.4A at 70 kDa, whereas the tumor tissues displayed the band at the lower molecular weight. Survival analysis indicated that the C4.4A-positive ESCCs had significantly worse 5-year overall survival than the C4.4A-negative ESCC samples (P = 0.021) when using the C4.4A-GPI Ab, but not when using the C4.4A-119 Ab. This difference was most evident with membranous expression of C4.4A (P = 0.005). CONCLUSIONS: C4.4A expression was associated with a poor prognosis of ESCC when the GPI-related antibody was used. On the other hand, the C4.4A-119 Ab may be a useful diagnostic tool for ESCC because of its high detection rate.Annals of Surgical Oncology 02/2013; · 4.17 Impact Factor -
Article: Feasibility of laparoscopy-assisted total gastrectomy in patients with clinical stage I gastric cancer.
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ABSTRACT: BACKGROUND: Laparoscopy-assisted total gastrectomy (LATG) for gastric cancer is not yet widespread because of the technical difficulty of reconstruction. We have performed LATG on 100 patients with clinical stage I gastric cancer. This study investigated the short-term outcomes of LATG. METHODS: Between September 2001 and September 2012, 100 patients with clinical stage I gastric cancer underwent LATG with D1 plus beta or D2 lymphadenectomy. Roux-en-Y esophagojejunostomy was performed intracorporeally using end-to-side anastomosis with a circular stapler (the purse-string suture method). The primary endpoint was the proportion of postoperative complications during hospitalization. RESULTS: Mean operation time was 249 min; mean blood loss was 182 ml. There were no conversions to open surgery. According to the Clavien-Dindo classification, there were 8 grade II (8 %) and 10 grade IIIa/b (10 %) complications. There were no treatment-related deaths or grade IV complications. The most frequent complication was anastomotic or stump leakage (6 %), followed by pancreatic fistula (5 %). Reoperations were required in two patients with leakage. CONCLUSIONS: The short-term outcomes of LATG in our study involving 100 patients were outlined. LATG for gastric cancer patients should be attempted preferably in a clinical trial setting by surgeons with sufficient experience in laparoscopic gastrectomy.Gastric Cancer 02/2013; · 2.42 Impact Factor -
Article: C4.4A Expression Is Associated with a Poor Prognosis of Esophageal Squamous Cell Carcinoma.
Annals of Surgical Oncology 01/2013; · 4.17 Impact Factor -
Article: Larynx-Preserving Limited Resection and Free Jejunal Graft For Carcinoma of the Cervical Esophagus.
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ABSTRACT: BACKGROUND: There is no generally accepted treatment strategy for cervical cancer. The aim of this study was to evaluate the safety and efficacy of larynx-preserving limited resection with free jejunal graft for cervical esophageal cancer. METHODS: We retrospectively reviewed data of 58 patients with cervical esophageal cancer who underwent limited resection and free jejunal graft with or without laryngeal preservation. Among them, 45 patients received neoadjuvant treatment. RESULTS: Larynx-preserving surgery was conducted in 33 of the 58 patients (56.9 %). A higher proportion of patients who underwent laryngopharyngectomy with cervical esophagectomy (larynx-nonpreserving group) had cT4 tumors than those who underwent larynx-preserving cervical esophagectomy (larynx-preserving group) (72 vs. 12 %). The overall incidence of postoperative complications was similar in the two groups (56 vs. 52 %). The 5-year survival rate was 44.9 % for the entire group. Laryngeal preservation did not reduce overall survival compared with the larynx-nonpreserving operation (5-year survival rate: 57.8 vs. 25.8 %). Multivariate analysis identified the number of metastatic lymph nodes as the only independent prognostic factor. CONCLUSIONS: The present study demonstrated that larynx-preserving limited resection with free jejunal graft is feasible. Also, this approach did not worsen the prognosis compared with the larynx-nonpreserving operation. Limited resection with free jejunal graft and laryngeal preservation is a promising treatment strategy for cervical esophageal cancer.World Journal of Surgery 12/2012; · 2.36 Impact Factor -
Article: A case of simultaneous transvaginal NOTES gastrectomy and vaginal hysterectomy in a patient with gastric submucosal tumor and uterine prolapse.
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ABSTRACT: A 5-cm gastric submucosal tumor was incidentally found through abdominal CT as a preoperative work-up for hysterectomy in a 62-year-old woman with uterine prolapse. NOTES using a flexible gastrointestinal endoscope via the transvaginal route was indicated to accomplish concomitant partial gastrectomy and hysterectomy. Perigastric dissection was performed, followed by stapled partial gastrectomy using transvaginal NOTES technique with two transabdominal ports. The specimen was delivered transvaginally by enlarging the initial vaginal entry site. Vaginal hysterectomy was then accomplished by utilizing the enlarged vaginal wound. The patient showed rapid and uneventful postoperative recovery without any narcotic need. No complication was noted, her cosmetic result was satisfactory, and there was complete resolution of preoperative gynecological symptoms. Female patients with concomitant gastrointestinal and gynecological conditions requiring large specimen retrieval would potentially be suitable candidates for the transvaginal NOTES approach.Asian Journal of Endoscopic Surgery 11/2012; 5(4):168-71. -
Article: Comparison of Billroth I and Roux-en-Y Reconstruction after Distal Gastrectomy for Gastric Cancer: One-year Postoperative Effects Assessed by a Multi-institutional RCT.
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ABSTRACT: PURPOSE: This randomized, controlled trial evaluated the clinical efficacy of Billroth I (BI) and Roux-en-Y (RY) reconstruction at 1 year after distal gastrectomy for gastric cancer. METHODS: The primary end point was the amount of body weight lost at 1 postoperative year, and secondary end points included other items related to nutritional status such as serum albumin and lymphocyte count, as well as endoscopic examination findings of the remnant stomach and esophagus. Of the 332 patients enrolled, 163 were assigned to the BI group and 169 were randomized to the RY group. RESULTS: The loss in body weight 1 year after surgery did not differ significantly between the BI and RY groups (9.1 % and 9.7 %, respectively, p = 0.39). There were no significant differences in other aspects of nutritional status between the 2 groups. Endoscopic examination 1 year after gastrectomy showed reflux esophagitis in 26 patients (17 %) in the BI group versus 10 patients (6 %) in the RY group (p = 0.0037), while remnant gastritis was observed in 71 patients (46 %) in the BI group versus 44 patients (28 %) in the RY group (p = 0.0013); differences were significant for both conditions. Multivariable analysis showed that the only reconstruction was the independently associated factor with the incidence of reflux esophagitis. CONCLUSIONS: RY reconstruction was not superior to BI in terms of body weight change or other aspects of nutritional status at 1 year after surgery, although RY more effectively prevented reflux esophagitis and remnant gastritis after distal gastrectomy.Annals of Surgical Oncology 10/2012; · 4.17 Impact Factor -
Article: Overexpression of Forkhead Box M1 Transcription Factor (FOXM1) is a Potential Prognostic Marker and Enhances Chemoresistance for Docetaxel in Gastric Cancer.
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ABSTRACT: BACKGROUND: Mammalian forkhead box transcription factor 1 (FoxM1) has been overexpressed and correlated with pathogenesis in a variety of human malignancies. We investigated the expression status and clinical significance of its overexpression in gastric adenocarcinoma. Furthermore, we demonstrated correlations between FoxM1 overexpression and drug resistance to chemotherapeutic agents in gastric cancer cells and gastric cancer patients treated with chemotherapy. METHODS: Fifty-three (69 %) of 77 tumors were diagnosed as positive for FoxM1 by immunohistochemistry. Multivariate analysis identified FoxM1 expression as a significant independent prognostic predictor for overall and disease-free survival in gastric cancer patients (hazard ratio 3.9 and 3.5, respectively). Furthermore, we investigated associations between FoxM1 overexpression and clinical response of chemotherapy for patients with advanced gastric cancer. RESULTS: Our clinical results showed that FoxM1 overexpression was significantly associated with resistance in chemotherapy of docetaxel in addition to 5-fluorouracil (5-FU) plus S-1 plus cisplatin (CDDP) and was not significant in chemotherapy of 5-FU plus CDDP for patients with advanced gastric cancer. In vitro experiments showed that Mkn7 transfected FoxM1 siRNA significantly reduced chemoresistance to docetaxel over that with parental cell lines and Mkn45 transfected with FoxM1 significantly enhanced chemoresistance to docetaxel over that with parental cell lines. CONCLUSIONS: Our study showed that FoxM1 was an independent prognostic factor in gastric cancer. Furthermore, we showed that FoxM1 was a critical molecule for chemoresistance to a microtubule-stabilizing anticancer agent, docetaxel. Taken together, those results suggest that inhibition of overexpressed FoxM1 will be a promising therapeutic strategy for advanced gastric cancer.Annals of Surgical Oncology 10/2012; · 4.17 Impact Factor -
Article: Evaluation of Dysphagia and Diminished Airway Protection after Three-Field Esophagectomy and a Remedy.
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ABSTRACT: BACKGROUND: Recently, reports from the West have indicated three-field lymphadenectomy (3FL) for esophageal cancer increases the accuracy of tumor staging and survival. However, this cervical procedure is likely to lead to swallowing dysfunction and aspiration, which are barriers to introducing this procedure in clinical practice. METHODS: Our goal is to elucidate the etiology of swallowing dysfunction after 3FL and devise a remedy. First, based on evaluation of swallowing function in ten patients with two-field lymphadenectomy (2FL) and ten with 3FL, we hypothesized that the scarred sternohyoid and sternothyroid muscles might be impairing laryngeal elevation after 3FL; thus, complete division of the bilateral infrahyoid muscles attached to the sternum (CDBIMS) could be an effective remedy. Next, the utility of this additive procedure was examined in 20 patients with 3FL. Swallowing function was evaluated by the distance of total laryngeal elevation (TLE) and the frequency of incomplete airway protection (IAP) (laryngeal penetration or aspiration) on videofluoroscopic study. RESULTS: The average TLE and frequency of IAP were, respectively, 0.37 cm and 70 % in the 3FL group, showing significant deterioration (p < 0.001 and 0.025), in contrast to 1.79 cm and 20 % in the 2FL group. The 3FL + CDBIMS group showed significant improvements in the average TLE and the frequency of IAP (1.70 cm and 25 %), compared with the 3FL group (p < 0.001 and 0.018). Multivariate logistic regression identified additive CDBIMS as a significant suppressor of IAP after 3FL. CONCLUSIONS: Laryngeal elevation was significantly impaired after 3FL. Adding CDBIMS might improve swallowing function in these patients.World Journal of Surgery 10/2012; · 2.36 Impact Factor -
Article: Gastric schwannomas revisited: has precise preoperative diagnosis become feasible?
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ABSTRACT: BACKGROUND: Gastric schwannomas are not common but are clinically important in terms of differential diagnosis from other submucosal lesions. The precise preoperative diagnosis, however, has been challenging mainly owing to the lack of specific findings in conventional imaging studies. The aim of this study was to revisit the possibilities and limitations of modern preoperative diagnostic modalities for gastric schwannomas. METHODS: Fourteen consecutive patients with a final pathological diagnosis of gastric schwannoma were retrospectively analyzed. Data included demographics, preoperative imaging studies/diagnosis, surgery, histopathology, and follow-up results. RESULTS: The series included 6 males and 8 females, with a median age of 49 years (range 26-68 years). No symptoms were presented, except for 1 patient with epigastric pain. The tumors were located in the upper (n = 5), middle (3), and lower stomach (6), with a median size of 41 mm (range 20-75 mm). Twelve schwannomas (86 %) showed homogeneous enhancement on computed tomography. Ulceration was seen on endoscopy in 4 of 12 available cases (33 %). Positron emission tomography was performed in the last 4 patients, showing fluorodeoxy-glucose uptake in all cases (100 %). A preoperative diagnosis of schwannoma was not obtained in the majority of cases (13/14, 93 %); only 1 case was correctly diagnosed, by endoscopic aspiration cytology. Laparoscopic partial gastrectomy was attempted and completed in 13 cases. The patients have been followed up for 4.7 years (range 2.1-20.3 years), with no recurrencesor metastases and acceptable gastrointestinal function. CONCLUSIONS: The precise preoperative diagnosis of gastric schwannomas remains difficult even with modern imaging studies. Surgery, therefore, should be positively considered for patients without a conclusive preoperative diagnosis.Gastric Cancer 08/2012; · 2.42 Impact Factor -
Article: Effect of rikkunshito, a Japanese herbal medicine, on gastrointestinal symptoms and ghrelin levels in gastric cancer patients after gastrectomy.
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ABSTRACT: BACKGROUND: Gastric cancer patients who undergo gastrectomy suffer from a post-gastrectomy syndrome that includes weight loss, dumping syndrome, reflux esophagitis, alkaline gastritis, and finally malnutrition. It is important to ameliorate the post-gastrectomy symptoms to restore postoperative quality of life (QoL). The aim of this study was to investigate the effect of rikkunshito, a Japanese herbal medicine, on postoperative symptoms and ghrelin levels in gastric cancer patients after gastrectomy. METHODS: Twenty-five patients who had undergone gastrectomy received 2.5 g of rikkunshito before every meal for 4 weeks, and a drug withdrawal period was established for the next 4 weeks. Changes in gastrointestinal hormones, including ghrelin, and appetite visual analog scale scores were measured, and QoL was estimated by using the European Organization for Research and Treatment of Cancer core questionnaire QLQ-C30. The Dysfunction After Upper Gastrointestinal Surgery for Cancer (DAUGS) scoring system was used to evaluate gastrointestinal symptoms after gastrectomy. RESULTS: Sixteen men and nine women (mean age 61.9 years) were enrolled in the study. All patients had either stage I (n = 24) or II (n = 1) disease and had undergone either distal gastrectomy (n = 17) or total gastrectomy (n = 8) by a laparoscopy-assisted approach. The mean ratio of the acyl-/total ghrelin concentration increased significantly after rikkunshito administration (Pre: 7.8 ± 2.1, 4 weeks: 10.5 ± 1.7 %, p = 0.0026). The total DAUGS score, as well as the scores reflecting limited activity due to decreased food consumption, reflux symptoms, dumping symptoms, and nausea and vomiting significantly improved after rikkunshito administration. CONCLUSIONS: The present study demonstrated a significant attenuation of gastrointestinal symptoms after gastrectomy by treatment with rikkunshito. Rikkunshito is potentially useful to minimize gastrointestinal symptoms after gastrectomy.Gastric Cancer 08/2012; · 2.42 Impact Factor -
Article: Pattern of abdominal nodal spread and optimal abdominal lymphadenectomy for advanced Siewert type II adenocarcinoma of the cardia: results of a multicenter study.
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ABSTRACT: BACKGROUND: It remains uncertain whether radical lymphadenectomy combined with total gastrectomy actually contributes to long-term survival for Siewert type II adenocarcinoma of the cardia. We identified the pattern of abdominal nodal spread in advanced type II adenocarcinoma and defined the optimal extent of abdominal lymphadenectomy. METHODS: Eighty-six patients undergoing R0 total gastrectomy for advanced type II adenocarcinoma were identified from the gastric cancer database of 4,884 patients. Prognostic factors were investigated by multivariate analysis. The therapeutic value of lymph node dissection for each station was estimated by multiplying the incidence of metastasis by the 5-year survival rate of patients with positive nodes in each station. RESULTS: The overall 5-year survival rate was 37.1 %. Age less than 65 years [hazard ratio, 0.455 (95 % confidence interval (CI), 0.261-0.793)] and nodal involvement with pN3 as referent [hazard ratio for pN0, 0.129 (95 % CI, 0.048-0.344); for pN1, 0.209 (95 % CI, 0.097-0.448); and for pN2, 0.376 (95 % CI, 0.189-0.746)] were identified as significant prognosticators for longer survival. Perigastric nodes of the lower half of the stomach in positions 4d-6 were considered not beneficial to dissect, whereas there were substantial therapeutic benefits to dissecting the perigastric nodes of the upper half of the stomach in positions 1-3 and the second-tier nodes in positions 7 and 11. CONCLUSIONS: Limited lymphadenectomy attained by proximal gastrectomy might suffice as an alternative to extended lymphadenectomy with total gastrectomy for obtaining potential therapeutic benefit in abdominal lymphadenectomy for advanced Siewert type II adenocarcinoma.Gastric Cancer 08/2012; · 2.42 Impact Factor -
Article: Let-7 Expression Is a Significant Determinant of Response to Chemotherapy through the Regulation of IL-6/STAT3 Pathway in Esophageal Squamous Cell Carcinoma.
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ABSTRACT: Cisplatin-based chemotherapy is widely used for esophageal cancer, sometimes in combination with surgery/radiotherapy, but poor response to chemotherapy is not uncommon. The aim of this study was to examine whether miRNA expression is useful to predict the response to chemotherapy in patients with esophageal cancer. Using pretreatment biopsy samples from 98 patients with esophageal cancer who received preoperative chemotherapy, we measured the expression level of several miRNAs whose expression was altered in cisplatin-resistant esophageal cancer cell lines compared with those parent cell lines and examined the relationship between the miRNA expression and response to chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA-induced changes in chemosensitivity. The expression levels of 15 miRNAs were altered in cisplatin-resistant cells. Of these, low expression of let-7b and let-7c in before-treatment biopsies from 74 patients of the training set correlated significantly with poor response to chemotherapy, both clinically and histopathologically. Low expression of let-7c also correlated with poor prognosis (P = 0.032). The relationship between let-7b and let-7c expression and response to chemotherapy was confirmed in the other 24 patients of the validation set. In in vitro assay, transfection of let-7c restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin. Let-7c directly repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway. Let-7 expression in esophageal cancer can be potentially used to predict the response to cisplatin-based chemotherapy. Let-7 modulates the chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in esophageal cancer. Clin Cancer Res; 18(18); 5144-53. ©2012 AACR.Clinical Cancer Research 07/2012; 18(18):5144-53. · 7.74 Impact Factor -
Article: Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer.
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ABSTRACT: The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A*2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55%) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100% after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82%) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82%) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.International Journal of Oncology 07/2012; · 2.40 Impact Factor -
Article: Use of fibrin glue sealant with polyglycolic acid sheets to prevent pancreatic fistula formation after laparoscopic-assisted gastrectomy.
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ABSTRACT: PURPOSE: A pancreatic fistula is a serious postoperative complication that can occur after gastrectomy with lymphadenectomy for gastric cancer. The aim of this prospective study was to analyze the usefulness of the local application of fibrin glue sealant (FG) and polyglycolic acid sheets (PAS) in preventing pancreatic fistula formation after gastrectomy. PATIENTS AND METHODS: The surface of the pancreas was covered with FG and PAS after peri-pancreatic lymph node dissection in 34 patients (F/P group). The postoperative outcome was compared with historical control subjects who did not receive the same application (control group, 64 patients). RESULTS: A pancreatic fistula occurred in three patients in the control group but in none the F/P group (P = 0.049). The volume of drainage fluid on postoperative day (POD) 1 and 3 was smaller in the F/P group than in the control group (POD1: F/P group, 80 ml; control: 150 ml, P < 0.001; POD3: 60 vs. 120 ml, P < 0.001). The amylase levels in the drainage fluid on POD1 and 3 were also significantly lower in the F/P group than in the control group (POD1: F/P group, 660 U/L; control: 1220 U/L, P = 0.030; POD2: 270 vs. 830 U/L, P = 0.038; POD3, 160 vs. 630 U/L, P = 0.041). CONCLUSION: The application of FG and PAS after LAG helps to prevent pancreatic fistula formation.Surgery Today 07/2012; · 1.22 Impact Factor -
Article: Clinical trial of the intratumoral administration of labeled DC combined with systemic chemotherapy for esophageal cancer.
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ABSTRACT: Esophageal cancer is a highly aggressive disease, and improved modalities for its treatment are needed. We performed chemoimmunotherapy involving the intratumoral administration of 111In-labeled dendritic cells (DC) in combination with preoperative chemotherapy in 5 esophageal cancer patients. Mature DC were generated and traced by scintigraphy after their administration. No adverse events that were directly related to the intratumoral DC administration were observed. Delayed-type hypersensitivity skin tests against keyhole limpet hemocyanin, which was added to the culture medium, detected a positive response in 3 patients, and keyhole limpet hemocyanin antibody production was observed in 4 patients, suggesting that intratumorally administered DC migrate to the lymph nodes, where they function as antigen-presenting cells. However, scintigraphic images obtained after the DC administration demonstrated that the DC remained at the esophageal tumor injection sites in all cases, and no DC accumulation was observed elsewhere. The accumulation of CD83+ cells in the primary tumor was also observed in 2 out of 4 patients in an immunohistochemical analysis using surgically resected specimens. Although the induction of tumor-specific immune responses during chemoimmunotherapy was also analyzed in enzyme-linked immunosorbent assay against 28 tumor antigens, none of the antibodies against the antigens displayed enhanced titers. No changes of NY-ESO-1-specific cellular immune response was observed in a patient who displayed NY-ESO-1 antibody production before the DC administration. These results suggest that the intratumoral administration of 111In-labeled mature DC during chemotherapy does not lead to detectable DC migration from the primary tumor to the draining lymph nodes, and therefore, might not achieve an optimal clinical response.Journal of immunotherapy (Hagerstown, Md.: 1997) 07/2012; 35(6):513-21. · 3.20 Impact Factor -
Article: Single-port laparoscopic surgery of the distal esophagus: initial clinical experience.
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ABSTRACT: Laparoscopic fundoplication (LF) is considered to be potentially suitable for single-port surgery because of lack of requirements of organ resection, anastomosis, and specimen retrieval. However, its feasibility and safety have not been fully established. The objective of this study was to evaluate the feasibility and safety of single-port LF (sLF) in our institution. sLF was attempted in 11 patients and was completed without the additional ports in 3 patients (27%). The remaining 8 patients required the addition of 1 to 3 ports to complete LF. Median operating time and blood loss were 221 minutes and 20 mL, respectively (intention-to-treat). No major complications were noted. All patients showed uneventful postoperative recovery and clinical improvement of their preoperative symptoms with satisfactory cosmetic outcome. sLF is technically feasible and safe, although the use of extra ports should be positively considered to ensure the safety and quality of LP.Surgical laparoscopy, endoscopy & percutaneous techniques 06/2012; 22(3):e118-21. · 1.23 Impact Factor -
Article: Laparoscopic intragastric surgery revisited: its role for submucosal tumors adjacent to the esophagogastric junction.
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ABSTRACT: When the gastric submucosal tumor (SMT) locates adjacent to the esophagogastric junction (EGJ), it is difficult to preserve EGJ technically and oncologically. In this study, we describe our clinical experience with laparoscopic intragastric surgery (LIGS) and discuss its role for gastric SMTs adjacent to EGJ. A retrospective review was performed on patients who underwent surgical treatment of gastric SMTs adjacent to EGJ (April 1994 to May 2010). They were divided into 3 groups: laparoscopic partial gastrectomy (LAP, n=10), LIGS (n=10), and open laparotomy (OPEN, n=7), respectively. The completion rates were 50% in LAP and 90% in LIGS. Overall preservation rate of EGJ was 80% (LAP), 100% (LIGS), and 29% (OPEN), respectively. The patients who underwent total/proximal mastectomy showed significantly higher incidence of postoperative gastrointestinal symptoms, which required long-term medication. LIGS stays as a valuable alternative and would be an attractive option for gastric SMTs adjacent to EGJ.Surgical laparoscopy, endoscopy & percutaneous techniques 06/2012; 22(3):251-4. · 1.23 Impact Factor
Top co-authors
Top Journals
Institutions
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2002–2013
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Osaka University
- • Gastroenterological Surgery
- • Department of Mechanical Science and Bioengineering
- • Department of Integrated Medicine
Ibaraki, Osaka-fu, Japan
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2012
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Osaka National Hospital
Ōsaka-shi, Osaka-fu, Japan
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2006–2012
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Osaka City University
- Department of Gastroenterological Surgery
Ōsaka-shi, Osaka-fu, Japan
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