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Kitayama J.,University of Tokyo | Emoto S.,University of Tokyo | Yamaguchi H.,University of Tokyo | Ishigami H.,University of Tokyo | And 5 more authors.
Annals of Surgical Oncology | Year: 2015

Background: The frequency of intraperitoneal free tumor cells (IPTC) is considered to reflect the severity of peritoneal metastasis (PM). We quantified the relative number of IPTC against leukocytes in peritoneal fluid and evaluated its clinical relevance in gastric cancer (GC) patients, particularly those with PM. Methods: Cells recovered from ascites or peritoneal lavage fluid were immunostained with monoclonal antibodies (mAb) to CD45 and CD326 (EpCAM). Using flow cytometry (FACS), CD326(+) and CD45(+) cells were classified as either tumor cells (T) or leukocytes (L) and the T/L ratio (TLR) was calculated in a total of 506 samples obtained from 300 patients with GC and 33 patients with liver cirrhosis (LC). Results: Median (M) of the TLR of the initial samples obtained from 199 patients with PM(+) GC was 1.32 % (0–1,868.44 %), which was significantly higher than that in patients with PM(−) GC (M = 0 %, 0–0.35 %; n = 101) or LC (M = 0 %, 0–0.031 %; n = 33). In 104 PM(+) patients who received combination chemotherapy including intraperitoneal paclitaxel, the TLR was repeatedly measured in peritoneal fluid obtained from the port. In these patients, the TLR showed a strong correlation with clinical features as well as cytological findings and carcinoembryonic antigen messenger RNA status. Finally, the median survival time of the 11 patients with initial TLR > 10 % was significantly shorter than that of the 52 patients with TLR < 10 % (271 vs. 627 days; p = 0.0002). Conclusion: The TLR excellently reflected tumor burden in the peritoneal cavity, and could be a reliable biomarker to determine the outcome, as well as the effectiveness, of chemotherapy in patients with PM(+) GC. © 2014, Society of Surgical Oncology. Source


Hyodo I.,University of Tsukuba | Morita T.,Palliative Care Team and Seirei Hospice | Adachi I.,Shizuoka Cancer Center | Shima Y.,Tsukuba Medical Center | And 2 more authors.
Japanese Journal of Clinical Oncology | Year: 2010

Objective: To develop a predicting tool for survival of terminally ill cancer patients. Methods: This prospective, multicenter study was composed of two cohorts of samples: development and test. In the development sample of terminally ill cancer patients, 32 candidate predictors were studied to develop a new tool, Japan Palliative Oncology Study Prognostic Index using the Cox proportional hazard model. Then the test sample was studied to validate Japan Palliative Oncology Study-Prognostic Index and compared it with the conventional predicting tools, such as palliative prognostic score and simplified palliative prognostic index. Results: Five significant predictors, physician's clinical prediction of survival, consciousness, pleural effusion, white blood cell count and lymphocyte % were derived from the analysis of 201 patients, and Japan Palliative Oncology Study-Prognostic Index was developed using these predictors. It could divide patients into three risk groups: low (A), intermediate (B) and high (C). Median survival times for Groups A, B and C were 51, 35 and 16 days, respectively. Survival probability for more than 30 days for Groups A, B and C in the development sample was 78%, 61% and 16%, respectively. Japan Palliative Oncology Study-Prognostic Index was studied in subsequent 208 patients for the test sample, and constant results (median survival times for Groups A, B and C; 67, 31 and 10 days, and survival probability for more than 30 days for Groups A, B and C; 81, 48 and 11%) were obtained. Palliative prognostic score can also predict three risk groups well, but simplified palliative prognostic index could not discriminate low risk from intermediate risk group. Conclusion: Japan Palliative Oncology Study-Prognostic Index, a tool to predict survival, has been developed. Its reliability should be confirmed further in the future study, comparing with palliative prognostic score. © The Author (2010). Published by Oxford University Press. All rights reserved. Source


Kitayama J.,Jichi Medical University | Yamaguchi H.,Jichi Medical University | Ishigami H.,University of Tokyo | Matsuzaki K.,Kanamecho Hospital | Sata N.,Jichi Medical University
PLoS ONE | Year: 2016

The human peritoneal cavity contains a small number of free cells of mesenchymal cell lineage. Intraperitoneal mesenchymal cells (PMC) play supportive roles in metastasis formation on the peritoneum. In this study, we found that PMC, when co-cultuerd with human gastric cancer cells, MKN45, enhanced the proliferation of MKN45 when cultured at low, but not high, cellular density. Also, PMC suppressed apoptotic cell death of MKN45 only under low density culture conditions. Time-lapse videoanalysis clearly demonstrated that PMC randomly migrated more vigorously than did MKN45, and strongly enhanced the migration behavior of co-cultured MKN45. In fact, the majority of MKN45 migrated together in direct physical contact with PMC, and the sum of migration lengths from original position of co-cultured MKN45 for 48 hours was approximately 10 times longer than that of MKN45 cultured alone. Our data suggest that enhanced migration can increase the chance of direct contact or positional proximity among sparcely distributed MKN45, which may bring survival advantages to tumor cells. This may be one of the important mechanisms of peritoneal metastasis, since only a small number of tumor cells are considered to be disseminated in the early step of metastasis formation on the peritoneum. © 2016 Kitayama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Kitayama J.,University of Tokyo | Emoto S.,University of Tokyo | Yamaguchi H.,University of Tokyo | Ishigami H.,University of Tokyo | And 5 more authors.
Cytometry Part B - Clinical Cytometry | Year: 2014

Background Peritoneal metastasis (PM) is the most life-threatening type of metastasis in abdominal malignancy. To improve the diagnostic accuracy of cytologic detection (CY) of free tumor cells (FTC) in the peritoneal cavity, we tried to quantify the FTC to leukocyte ratio using flow cytometry in patients with peritoneal metastasis. Methods Cells were recovered from ascites or peritoneal lavages from 106 patients who underwent abdominal surgery and additional 89 samples which were obtained from peritoneal catheter or access port in patients with PM (+) gastric cancer. The cells were immunostained with monoclonal antibodies to CD45 and to CD326 (EpCAM). Using flow cytometry, CD326 (+) and CD45 (+) cells were classified as either tumor cells (T) or leukocytes (L) and the T/L ratio (TLR) was calculated. Results In 106 samples obtained by laparotomy, Median (M) of the TLR of PM (+) patients was 1.39% (0-807.87%) which was significantly higher than PM (-) patients (M=0%, 0-2.14%, P < 0.001). In PM (+) patients, 86 CY (+) samples showed higher TLR than 61 CY (-) samples (M=2.81%, 0.02-1868.44% vs. M=0%, 0-3.45%, p<0.0001). In all of the 24 patients who were monitored for TLR before and after intraperitoneal (IP) chemotherapy, the TLR was reduced which was more dramatic than the results of the change in cytology. Conclusions TLR measured with FACS is an excellent reflection of the tumor spread in the peritoneal cavity and could be a reliable diagnostic biomarker to determine the severity of PM as well as effectiveness of IP chemotherapy. © 2013 International Clinical Cytometry Society © 2013 International Clinical Cytometry Society. Source


Matsusaki K.,Hofu Institute of Gastroenterology | Ohta K.,International University of Health and Welfare | Yoshizawa A.,Kanamecho Hospital | Gyoda Y.,Kanamecho Hospital
International Journal of Clinical Oncology | Year: 2011

Background: We have actively carried out cell-free and concentrated ascites reinfusion therapy (CART) for refractory ascites. However, with conventional CART, the membrane becomes clogged after processing about 2 L of cancerous ascites fluid due to the fact that it is rich in cellular and mucous components; it is therefore difficult to process the entire volume of collected ascites. Methods: We developed KM-CART which includes a membrane cleaning function, and applied it in 73 cases of cancerous ascites, after its basic functions had been evaluated in 11 cases of refractory cancerous ascites. Results: On average, using KM-CART, 6.4 L (range 1.7-14.9 L) of ascites were filtrated and concentrated to 0.8 L (0.2-2.0 L) in 57 min (5-129 min); the membrane was cleaned an average of three times (range 0-10 times) and this enabled the processing of more ascites in a shorter period. In addition, the circuit and the handling were both markedly simple, and fever, which has been the most notable adverse effect with the conventional system, was not an issue. Conclusion: Since KM-CART was safe and is expected to improve the subjective symptoms and general condition of the patient, it is proposed that this novel system should actively be used not only for palliation but also as supplementary treatment for cancerous peritonitis. © 2011 Japan Society of Clinical Oncology. Source

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