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1.  Clinicopathological Analysis of Borrmann Type IV Gastric Cancer 
Borrmann type IV gastric cancer is often diagnosed only at an advanced stage, resulting in a prognosis poor. We performed a retrospective study of the clinical characteristics of Borrmann type IV gastric cancer and the prognostic factors affecting the survival rate in such patients.
Materials and Methods
Of 4,063 patients with all gastric cancers, 370 (9%) with Borrmann type IV gastric cancer were analyzed.
The clinical characteristics of these patients included a higher incidence rate in young females, and higher rates of serosa exposure, metastasis to lymph nodes and early peritoneal dissemination. Of patients presenting with peritoneal seeding, those resected had a higher survival rate than those that were not. A univariate analysis showed that the prognostic factors affecting the survival rate following a curative resection were the location, occupied area and depth of the primary tumor, as well as the presence of lymph node metastasis and the tumor stage. A multivariate analysis indicated that the tumor location and stage were significant independent prognostic factors after a curative resection for Borrmann type IV gastric cancer.
In conclusion, the early diagnosis and treatment of patients with Borrmann type IV gastric cancer are essential for the better survival of these patients. Even in patients with advanced tumors, a noncurative palliative resection may improve the prognosis.
PMCID: PMC2785394  PMID: 19956485
Borrmann type IV; Stomach neoplasms
2.  FAIRY: a randomized controlled patient-blind phase III study to compare the efficacy and safety of intravenous ferric carboxymaltose (Ferinject®) to placebo in patients with acute isovolemic anemia after gastrectomy - study protocol for a randomized controlled trial 
Trials  2014;15:111.
Isovolemic anemia (decrease in hemoglobin concentration with normal or even increased blood volume) after gastric cancer surgery may negatively influence short- and long-term outcomes. Therefore correction of isovolemic postoperative anemia is supposed to be beneficial. This prospective randomized placebo-controlled multicenter trial is designed to evaluate the efficacy of ferric carboxymaltose administration with the primary end point of successful hemoglobin level increase by 2 g/dl at 12 weeks after randomization.
Methods and design
Gastric cancer patients after oncologic resection and postoperative hemoglobin level ≥ 7 g/dl to <10 g/dl at postoperative days 5 to 7 will be eligible for trial inclusion. After randomization, 450 patients (225 per group) are going to be subjected either to administration of ferric carboxymaltose (treatment group) or normal (0.9%) saline (placebo group). Patients will be blinded to the intervention. Patients will undergo evaluation for hemoglobin level, hematology and quality of life assessment 3 and 12 weeks after randomization.
Correction of isovolemic postoperative anemia in gastric cancer patients after oncologic resection is considered to be beneficial. Administration of ferric carboxymaltose is considered to be superior to placebo for anemia correction without the possible risks of red blood cell transfusion. Further, improved quality of life for patients with quick recovery of hemoglobin levels is expected.
Trial registration
NCT01725789 (international: and NCCCTS-12-644 (NCC, Korea).
PMCID: PMC3992134  PMID: 24708660
Ferric carboxymaltose; Isovolemic postoperative anemia; Gastric cancer; Randomized controlled trial
3.  CD49fhigh Cells Retain Sphere-Forming and Tumor-Initiating Activities in Human Gastric Tumors 
PLoS ONE  2013;8(8):e72438.
Identification of gastric tumor-initiating cells (TICs) is essential to explore new therapies for gastric cancer patients. There are reports that gastric TICs can be identified using the cell surface marker CD44 and that they form floating spheres in culture, but we could not obtain consistent results with our patient-derived tumor xenograft (PDTX) cells. We thus searched for another marker for gastric TICs, and found that CD49fhigh cells from newly-dissected gastric cancers formed tumors with histological features of parental ones while CD49flow cells did not when subcutaneously injected into immunodeficient mice. These results indicate that CD49f, a subunit of laminin receptors, is a promising marker for human gastric TICs. We established a primary culture system for PDTX cells where only CD49fhigh cells could grow on extracellular matrix (ECM) to form ECM-attaching spheres. When injected into immunodeficient mice, these CD49fhigh sphere cells formed tumors with histological features of parental ones, indicating that only TICs could grow in the culture system. Using this system, we found that some sphere-forming TICs were more resistant than gastric tumor cell lines to chemotherapeutic agents, including doxorubicin, 5-fluorouracil and doxifluridine. There was a patient-dependent difference in the tumorigenicity of sphere-forming TICs and their response to anti-tumor drugs. These results suggest that ECM plays an essential role for the growth of TICs, and that this culture system will be useful to find new drugs targeting gastric TICs.
PMCID: PMC3756075  PMID: 24015244
4.  Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma – a randomized, controlled pilot study 
Mistletoe (Viscum album L.) extracts are widely used in complementary cancer therapy. Aim of this study was to evaluate safety and efficacy of a standardized mistletoe extract (abnobaVISCUM® Quercus, aVQ) in patients with gastric cancer.
Patients and Methods
32 operated gastric cancer patients (stage Ib or II) who were waiting for oral chemotherapy with the 5-FU prodrug doxifluridine were randomized 1:1 to receive additional therapy with aVQ or no additional therapy. aVQ was injected subcutaneously three times per week from postoperative day 7 to week 24 in increasing doses. EORTC QLQ-C30 and -STO22 Quality of Life questionnaire, differential blood count, liver function tests, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-2), CD 16+/CD56+ and CD 19+ lymphocytes were analyzed at baseline and 8, 16 and 24 weeks later.
Global health status (p <0.01), leukocyte- and eosinophil counts (p ≤0.01) increased significantly in the treatment group compared to the control group. Diarrhea was less frequently reported (7% vs. 50%, p=0.014) in the intervention group. There was no significant treatment effect on levels of TNF-alpha, IL-2, CD16+/CD56+ and CD 19+ lymphocytes and liver function tests measured by ANOVA.
Additional treatment with aVQ is safe and was associated with improved QoL of gastric cancer patients. ClinicalTrials.Gov Registration number NCT01401075.
PMCID: PMC3488325  PMID: 23033982
Qol; EORTC QLQ-C30; QLQ-STO22; 5-FU; Viscum album
5.  Treatment outcome of postoperative radiotherapy for retroperitoneal sarcoma 
Radiation Oncology Journal  2011;29(4):260-268.
To evaluate the treatment outcome and prognostic factor after postoperative radiotherapy in retroperitoneal sarcoma.
Materials and Methods
Forty patients were treated with surgical resection and postoperative radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008. Treatment volume was judged by the location of initial tumor and surgical field, and 45-50 Gy of radiation was basically delivered and additional dose was considered to the high-risk area.
The median follow-up period was 41.4 months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8% and disease free survival was 31.5%. The 5-year locoregional recurrence free survival was 61.9% and distant metastasis free survival was 50.6%. In univariate analysis, histologic type (p = 0.006) was the strongest prognostic factor for the OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also effect on the OS. Histologic type (p = 0.004) was unique significant prognostic factor for the actuarial local control.
Retroperitoneal sarcoma still remains as a poor prognostic disease despite the combined modality treatment including surgery and postoperative radiotherapy. Selective dose-escalation of radiotherapy or combination of effective chemotherapeutic agent must be considered to improve the treatment result especially for the histopathologic type showing poor prognosis.
PMCID: PMC3429911  PMID: 22984679
Sarcoma; Retroperitoneal; Radiotherapy; Postoperative; Outcome
6.  The effects of laparoscopic assisted total gastrectomy on surgical outcomes in the treatment of gastric cancer 
To evaluate the effectiveness of laparoscopic assisted total gastrectomy (LATG), we compared its early surgical outcomes with those of conventional open total gastrectomy (OTG) in patients who were diagnosed as having early gastric cancer preoperatively.
We retrospectively analyzed early surgical outcomes in 190 consecutive patients who underwent total gastrectomy for early gastric cancer between January 2009 to April 2010. The patients were divided into those who underwent LATG and those who underwent OTG. Their early surgical outcomes were analyzed to evaluate the effectiveness of LATG.
There was no significant difference in postoperative complication rates (P = 0.291). But in the analysis of other early surgical outcomes, we found that LATG could improve time to first flatus (P < 0.001), time to commencement of soft diet (P = 0.034), administration of analgesics (P = 0.024), pain score (Numeric Rating Scale), and hospital discharge (P = 0.045).
Although LATG didn't show better results for postoperative complications than those of OTG, LATG contributes to the improvement of early surgical outcomes, including bowel movement, pain score and hospital discharge. Therefore, we suggest that LATG could be a method to improve early surgical outcomes in patients who need total gastrectomy.
PMCID: PMC3204674  PMID: 22066043
Early gastric cancer; Laparoscopic assisted total gastrectomy; Open total gastrectomy
7.  Positioning During CT Gastrography in Patients with Gastric Cancer: the Effect on Gastric Distension and Lesion Conspicuity 
Korean Journal of Radiology  2009;10(3):252-259.
We wanted to prospectively evaluate the effect of various positions of the patient on gastric distension and lesion conspicuity during performance of CT gastrography (CTG).
Materials and Methods
One hundred thirteen consecutive patients with gastric cancer underwent CTG in the 30° left posterior oblique (LPO), supine, and prone positions. Two radiologists scored (a grade from 1-4) the degree of gastric distension and the lesion conspicuity according to the three scanning positions and the three gastric portions. Two- (2D) and three-dimensional (3D) images were used for analysis. Finally, these data were compared with the endoscopic findings and surgical results.
The mean scores of gastric distension and lesion conspicuity for the LPO and supine positions were higher than those for the prone position (p < 0.001) in the gastric middle and lower portions. However, there was no significant difference between the LPO and supine positions (p ≥ 0.21). As for the gastric upper portion, the mean scores of gastric distension in the prone position were higher than those in the two other positions (p < 0.001). The prone position showed better lesion conspicuity than the two other positions for only one of two cases of gastric cancer in the upper portion of the stomach.
CTG performed in the LPO position or the supine position combined with CTG performed in the prone position is optimal for achieving good gastric distension and evaluating the lesion conspicuity of gastric cancer.
PMCID: PMC2672180  PMID: 19412513
Computed tomography (CT), gastrography; Gastric cancer; Distension; Lesion conspicuity
8.  Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors of the Stomach: Report of Three Cases 
Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.
PMCID: PMC2741673  PMID: 19771279
Gastrointestinal stromal tumors; Imatinib; Neoadjuvant therapy; Surgery
9.  Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy 
Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy.
Materials and Methods
A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m2 IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy.
A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%.
Docetaxel, 75 mg/m2, is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.
PMCID: PMC2785917  PMID: 19956514
Stomach neoplasms; Docetaxel; Salvage therapy; Drug therapy

Results 1-9 (9)