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Yoshie K, Ishihara K. [Solubilization of Poorly Water-soluble Drugs with Amphiphilic Phospholipid Polymers]. YAKUGAKU ZASSHI 2023; 143:745-756. [PMID: 37661440 DOI: 10.1248/yakushi.23-00023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Most drug candidates developed in recent years are poorly water-soluble, which is a key challenge in pharmaceutical science. Various solubilization methods have been investigated thus far, most of which require solubilizers that provide a local hydrophobic environment wherein a drug can dissolve or induce interactions with drug molecules. We have focused on amphiphilic 2-methacryloyloxyethyl phosphoryl choline (MPC) polymers. In addition to the ease of molecular design of amphiphilic MPC polymers owing to their chemical structures, they have been reported to possess high biocompatibility in various biomaterial applications. Additionally, amphiphilic MPC polymers have been applied in the pharmaceutical field, especially in solubilization. We have qualitatively and quantitatively evaluated the effects of the chemical structure and physical properties of the solubilizer on the MPC polymers. In particular, MPC polymers with different chemical structures were designed and synthesized. The inner polarity and molecular mobility in the polymer aggregates were evaluated, indicating that the intrinsic properties reflect the chemical structure of the polymer. Additionally, amphiphilic MPC polymers were used to improve the solubility of poorly water-soluble drugs and as solid dispersion carriers, and they exhibited superior solubilizing abilities compared to a commonly used polymer. Furthermore, the solubility of biopharmaceuticals, such as peptides, was improved. It is possible to design and synthesize optimal structures based on the polarity of the hydrophobic environment and the intermolecular interaction with a drug. This research provides a unified interpretation of drugs and efficiently summarizes knowledge about drug development, which will facilitate the efficient and rapid development of drug formulations.
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Affiliation(s)
- Kensuke Yoshie
- Formulation Technology Research Laboratories, Daiichi Sankyo., Ltd
| | - Kazuhiko Ishihara
- Department of Materials Engineering, School of Engineering, The University of Tokyo
- Division of Materials and Manufacturing Science, School of Engineering, Osaka University
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Kinami S, Nakamura N, Miyashita T, Kitakata H, Fushida S, Fujimura T, Iida Y, Inaki N, Ito T, Takamura H. Life prognosis of sentinel node navigation surgery for early-stage gastric cancer: Outcome of lymphatic basin dissection. World J Gastroenterol 2021; 27:8010-8030. [PMID: 35046627 PMCID: PMC8678813 DOI: 10.3748/wjg.v27.i46.8010] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/28/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer. In this method, the dyed lymphatic system is dissected en bloc, and sentinel nodes are identified at the back table (ex vivo). Even with lymphatic basin dissection, blood flow to the residual stomach can be preserved, and function-preserving curative gastrectomy can be performed. The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated. We hypothesized that the oncological safety of sentinel node navigation surgery (SNNS) is not inferior to that of the guidelines. AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery. METHODS This was a retrospective cohort study. Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016. Patients from April 1999 to August 2008 were from the Department of Surgery II, Kanazawa University Hospital, and patients from August 2009 to March 2016 were from the Department of Surgical Oncology, Kanazawa Medical University Hospital. Patients who were diagnosed with gastric cancer, which was preoperatively diagnosed as superficial type (type 0), 5 cm or less in length, clinical T1-2 and node negative, and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected. The overall survival (OS) and relapse-free survival (RFS) of these patients (SNNS group) were investigated. Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group. RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included. Pathological nodal metastasis was observed in 10.5% and 10.4% of the SNNS and control groups, respectively. The diagnostic abilities of sentinel node biopsy were 84% and 98.6% for sensitivity and accuracy, respectively. In the SNNS group, 81.6% of patients underwent modified gastrectomy or function-preserving curative gastrectomy with lymphatic basin dissection, in which the extent of nodal dissection was further reduced compared to the guidelines. The OS rate in the SNNS group was 96.8% at 5 years and was significantly better than 91.3% in the control group (P = 0.0014). The RFS rates were equal in both groups. After propensity score matching, there were 231 patients in both groups, and the cumulative recurrence rate was 0.43% at 5 years in the SNNS group and 1.30% in the control group, which was not statistically different. CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.
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Affiliation(s)
- Shinichi Kinami
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Naohiko Nakamura
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Tomoharu Miyashita
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Hidekazu Kitakata
- Department of Gastroenterological Endoscopy, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Sachio Fushida
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa 920-8641, Ishikawa, Japan
| | - Takashi Fujimura
- Department of Surgery, Toyama City Hospital, Toyama 939-8511, Toyama, Japan
| | - Yasuo Iida
- Department of Mathematics, Division of General Education, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa 920-8641, Ishikawa, Japan
| | - Toru Ito
- Department of Gastroenterological Endoscopy, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Hiroyuki Takamura
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
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He C, Zou Z, Xia S, Xing X, Hu S, Hu Z, Li Y, Li S, Zhang H, Yang Y, Liu Y, Xu X, Liu B, Wang Y, Xu Y, Du X. Application of highly efficient and lowly toxic bufadienolides screened from toad skin in lymphatic chemotherapy for colorectal cancer through a lymphatic metastatic model. Int Immunopharmacol 2019; 70:241-251. [PMID: 30851704 DOI: 10.1016/j.intimp.2019.02.036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 02/14/2019] [Accepted: 02/22/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND Lymph node metastasis (LNM) remains a major obstacle to treat colorectal cancer (CRC). Increasing evidences have suggested that bufadienolides contain several fractions displaying antitumor activity and may be applied in lymphatic chemotherapy. However, effects of the highly efficient and lowly toxic (HELT) bufadienolides on CRC in lymphatic chemotherapy have not been reported. METHODS Adenosine triphosphate tumor chemosensitivity assays (ATP-TCA) was performed to detect the inhibition rate (IR) of fractions of bufadienolides to cytokine-induced killer (CIK) cells and tumor cells. HELT fraction-loaded emulsions of different concentrations were prepared. Nude mouse bearing HCT116 tumors in footpad received high-dose emulsion (HD-E), middle-dose emulsion (MD-E), low-dose emulsion (LD-E), control emulsion (CE), Cinobufacini Injection (CI), or normal saline (NS), respectively. Hematoxylin and eosin (H&E) staining, Flow Cytometry (FCM), enzyme-linked immune sorbent assay (ELISA) and hematological examination were applied to evaluate therapeutic effects and potential toxicity. RESULTS F18 and F19 were screened out as HELT fractions in vivo and F18-loaded emulsions of different concentrations for lymphatic administration were prepared. We confirmed that HD-E and MD-E produced obvious antitumor activities in footpad tumors and LNM compared with other groups in vitro. We also verified the effects of F18-loaded emulsions on activating hematopoietic function, stimulating proliferation of the spleen and natural killer (NK) cells, and promoting the secretion of IFN-γ and IgG1, although HD-E performed mild toxicity on liver. CONCLUSION The present study demonstrated that lymphatic chemotherapy with HELT fraction of bufadienolides could be an effective approach to the treatment of CRC patients with LNM.
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Affiliation(s)
- Changzheng He
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Zhenyu Zou
- Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, PR China
| | - Shaoyou Xia
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Xiaowei Xing
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Shidong Hu
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Zilong Hu
- Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
| | - Yuxuan Li
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Songyan Li
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Hongliang Zhang
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Yu Yang
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Yichen Liu
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Xiaolei Xu
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Boyan Liu
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Yufeng Wang
- Department of Patient Admission Management, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China
| | - Yingxin Xu
- Institute of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China.
| | - Xiaohui Du
- Department of General Surgery, Chinese General Hospital of People's Liberation Army, Beijing 100853, PR China.
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Aoyama J, Kawakubo H, Goto O, Nakahara T, Mayanagi S, Fukuda K, Suda K, Nakamura R, Wada N, Takeuchi H, Kitagawa Y. Potential for local resection with sentinel node basin dissection for early gastric cancer based on the distribution of primary sites. Gastric Cancer 2019; 22:386-391. [PMID: 30099636 DOI: 10.1007/s10120-018-0865-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 08/05/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Based on the sentinel node (SN) concept, function-preserving surgery with SN basin dissection (SNBD) can be performed for SN-negative early gastric cancers. Particularly, a resection area can be minimized when the SN basin and primary site are closely localized. The aim of this study was to compare probabilities of being candidates for local resection with SNBD based on tumor location among patients with early gastric cancer. METHODS We retrospectively analyzed 358 patients who underwent surgery with SN mapping for gastric cancer in our institution from November 1999 to April 2014. The proportion of patients who had a localized single basin and the distributions of the SN basins and primary sites were investigated. Patients with single basin drainage excluding remote sentinel node basin were considered as candidates for local resection with SNBD. RESULTS Of the 358 patients, 191 (53%) patients were considered eligible for local resection with SNBD. Patients with tumors located in the upper third of the stomach were more likely candidates for local resection than those with tumors in other locations (upper third, 68%; middle third, 50%; and lower third, 51%), whereas patients with tumors located in the anterior wall were less likely candidates than those with tumors other locations (anterior wall, 31%; posterior wall, 58%; greater curvature, 55%; and lesser curvature, 57%). CONCLUSION We found that > 50% of the patients indicated for SN navigation surgery, particularly those with tumors in the upper third of the stomach, potentially could undergo partial resection with SNBD.
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Affiliation(s)
- Junya Aoyama
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Osamu Goto
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Tadaki Nakahara
- Department of Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Shuhei Mayanagi
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Kazumasa Fukuda
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Koichi Suda
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Rieko Nakamura
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Norihito Wada
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hiroya Takeuchi
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
- Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Yuko Kitagawa
- Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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Ishihara K, Mu M, Konno T. Water-soluble and amphiphilic phospholipid copolymers having 2-methacryloyloxyethyl phosphorylcholine units for the solubilization of bioactive compounds. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2017; 29:844-862. [DOI: 10.1080/09205063.2017.1377023] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Kazuhiko Ishihara
- Department of Materials Engineering, School of Engineering, The University of Tokyo, Tokyo, Japan
- Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan
| | - Mingwei Mu
- Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan
| | - Tomohiro Konno
- Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan
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Kinami S, Kosaka T. Laparoscopic sentinel node navigation surgery for early gastric cancer. Transl Gastroenterol Hepatol 2017; 2:42. [PMID: 28616598 PMCID: PMC5460179 DOI: 10.21037/tgh.2017.05.02] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 04/07/2017] [Indexed: 12/18/2022] Open
Abstract
Currently, the most accurate method for identifying lymph node metastasis is intraoperative diagnosis by sentinel node (SN) biopsy. Based on the SNNS study-a recent large-scale, nationwide, multicenter prospective study-the SN concept seems to be scientifically valid in patients with early gastric cancer. SN biopsy is a multistep technique consisted of six essential elements: indication, the selection of a tracer, a proper tracer injection method, the objective detection of SNs, a reliable biopsy technique, and the precise detection of nodal metastasis. For SN biopsy of gastric cancer, these elements have been validated as follows: the indication should be limited to clinical T1 less than 4 cm in diameter; combination mapping with radioactive colloid and blue dye is used as the standard; and endoscopic submucosal injection is the standard tracer injection. Detection of SNs and a reliable biopsy technique are enabled by adaptation of lymphatic basin dissection, a proper biopsy technique for gastric cancer. Lymphatic basin dissection is a selective lymphadenectomy procedure for dissecting basins en bloc, collecting lymph nodes and lymphatic vessels stained with dye. Lymphatic basin dissection is superior to the ordinary pick-up method, not only for minimizing the rate of missed SNs, but also in terms of oncological safety as it complements an intraoperative frozen section diagnosis by serving as a backup dissection. Moreover, indocyanine green (ICG) fluorescence mapping has been developed in recent years. ICG fluorescence mapping is superior because of its high sensitivity and signal stability. Moreover, it is feasible for both open and laparoscopic gastrectomy in treating early gastric cancer. SN biopsy has brought dramatic changes to laparoscopic surgery for early gastric cancer. With laparoscopic SN biopsy using ICG fluorescence navigation, laparoscopic surgery for early gastric cancer has changed from the uniform standard gastrectomy with D1+ into a tailor-made function-preserving surgical procedure, such as local resection with lymphatic basin dissection.
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Affiliation(s)
- Shinichi Kinami
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku, Japan
| | - Takeo Kosaka
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku, Japan
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Lianos GD, Hasemaki N, Vaggelis G, Karampa A, Anastasiadi Z, Lianou A, Papanikolaou S, Floras G, Bali CD, Lekkas E, Katsios C, Mitsis M. Sentinel node navigation in gastric cancer: new horizons for personalized minimally invasive surgical oncology? Transl Gastroenterol Hepatol 2016; 1:91. [PMID: 28138656 PMCID: PMC5244601 DOI: 10.21037/tgh.2016.12.02] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Accepted: 11/24/2016] [Indexed: 12/23/2022] Open
Abstract
Complete (R0) resection and regional lymph nodes (LNs) dissection represent undoubtedly the basic surgical tools for patients with gastric cancer. It is reported that the LN metastasis rate in patients with early gastric cancer (EGC) is approximately 15-20%. Therefore, the innovative clinical application of sentinel node navigation surgery (SNNS) for EGC might be able to prevent unnecessary LN dissection as well as to reduce significantly the volume of gastric resection. Recent evidence suggests that double tracer methods appear superior compared to single tracer techniques. However, the researchers' interest is now focused on the identification of new LN detection methods utilizing sophisticated technology such as infrared ray endoscopy, fluorescence imaging and near-infrared technology. Despite its notable limitations, hematoxylin-eosin is still considered the mainstay staining for assessing the metastatic status of LNs. In this review, we summarize the current evidences and we provide the latest scientific information assessing safety, efficacy and potential limitations of the innovative sentinel node (SN) navigation technique for gastric cancer. We try also to provide a "view" towards a future potential application of personalized minimally invasive surgery in gastric cancer field.
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Affiliation(s)
- Georgios D. Lianos
- Department of Surgery, Ioannina University Hospital & University of Ioannina, Ioannina, Greece
- Department of Surgery, General Hospital of Preveza, Preveza, Greece
| | - Natasha Hasemaki
- Department of Surgery, General Hospital of Preveza, Preveza, Greece
| | | | | | - Zoi Anastasiadi
- Department of Surgery, Ioannina University Hospital & University of Ioannina, Ioannina, Greece
| | - Aikaterini Lianou
- Department of Surgery, Ioannina University Hospital & University of Ioannina, Ioannina, Greece
| | | | - Grigorios Floras
- Department of Surgery, General Hospital of Preveza, Preveza, Greece
| | - Christina D. Bali
- Department of Surgery, Ioannina University Hospital & University of Ioannina, Ioannina, Greece
| | | | - Christos Katsios
- Department of Surgery, Ioannina University Hospital & University of Ioannina, Ioannina, Greece
| | - Michail Mitsis
- Department of Surgery, Ioannina University Hospital & University of Ioannina, Ioannina, Greece
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C-C motif chemokine ligand 5 (CCL5) levels in gastric cancer patient sera predict occult peritoneal metastasis and a poorer prognosis. Int J Surg 2016; 32:136-42. [DOI: 10.1016/j.ijsu.2016.07.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 07/03/2016] [Indexed: 12/20/2022]
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KINAMI SHINICHI, OONISHI TOSHIO, FUJITA JUN, TOMITA YASUTO, FUNAKI HIROSHI, FUJITA HIDETO, NAKANO YASUHARU, UEDA NOBUHIKO, KOSAKA TAKEO. Optimal settings and accuracy of indocyanine green fluorescence imaging for sentinel node biopsy in early gastric cancer. Oncol Lett 2016; 11:4055-4062. [PMID: 27313740 PMCID: PMC4888277 DOI: 10.3892/ol.2016.4492] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Accepted: 04/08/2016] [Indexed: 02/07/2023] Open
Abstract
Indocyanine green (ICG) fluorescence imaging represents a promising method for sentinel node (SN) biopsy in laparoscopic gastric surgery due to its signal stability. In the present study, the suitability and optimal settings of ICG fluorescence imaging for SN biopsy in early gastric cancer were determined. Patients with single primary superficial-type adenocarcinoma of the stomach, lesions <5 cm in diameter, and no evident nodal metastasis and out of indication for endoscopic submucosal dissection were enrolled. The day prior to surgery, ICG solution was endoscopically injected into four quadrants of the submucosal layer of the tumor. The Photodynamic Eye was used to detect ICG fluorescence. Bright nodes were defined as clearly fluorescent nodes. A total of 72 patients were enrolled; 11 cases presented with metastasis, and of these, 10 could be diagnosed by bright node biopsy. The adequate concentration and injection volume of ICG was determined to be 50 µg/ml (×100) and 0.5 mlx4 points, respectively. There was 1 false-negative case, and this was attributed to the failure of the frozen section diagnosis. These results suggested that ICG fluorescence imaging for SN biopsy in laparoscopic surgery for early gastric cancer is feasible. However, a weakness of ICG fluorescence imaging is the subjectivity of bright node evaluation.
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Affiliation(s)
- SHINICHI KINAMI
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - TOSHIO OONISHI
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - JUN FUJITA
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - YASUTO TOMITA
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - HIROSHI FUNAKI
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - HIDETO FUJITA
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - YASUHARU NAKANO
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - NOBUHIKO UEDA
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
| | - TAKEO KOSAKA
- Department of Surgical Oncology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan
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Kwak Y, Nam SK, Shin E, Ahn SH, Lee HE, Park DJ, Kim WH, Kim HH, Lee HS. Comparison of the Diagnostic Value Between Real-Time Reverse Transcription-Polymerase Chain Reaction Assay and Histopathologic Examination in Sentinel Lymph Nodes for Patients With Gastric Carcinoma. Am J Clin Pathol 2016; 145:651-9. [PMID: 27247370 DOI: 10.1093/ajcp/aqw055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES Sentinel lymph node (SLN)-based diagnosis in gastric cancers has shown varied sensitivities and false-negative rates in several studies. Application of the reverse transcription-polymerase chain reaction (RT-PCR) in SLN diagnosis has recently been proposed. METHODS A total of 155 SLNs from 65 patients with cT1-2, N0 gastric cancer were examined. The histopathologic results were compared with results obtained by real-time RT-PCR for detecting molecular RNA (mRNA) of cytokeratin (CK)19, carcinoembryonic antigen (CEA), and CK20. RESULTS The sensitivity and specificity of the multiple marker RT-PCR assay standardized against the results of the postoperative histological examination were 0.778 (95% confidence interval [CI], 0.577-0.914) and 0.781 (95% CI, 0.700-0.850), respectively. In comparison, the sensitivity and specificity of intraoperative diagnosis were 0.819 (95% CI, 0.619-0.937) and 1.000 (95% CI, 0.972-1.000), respectively. The positive predictive value of the multiple-marker RT-PCR assay was 0.355 (95% CI, 0.192-0.546) for predicting non-SLN metastasis, which was lower than that of intraoperative diagnosis (0.813, 95% CI, 0.544-0.960). CONCLUSIONS The real-time RT-PCR assay could detect SLN metastasis in gastric cancer. However, the predictive value of the real-time RT-PCR assay was lower than that of precise histopathologic examination and did not outweigh that of our intraoperative SLN diagnosis.
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Affiliation(s)
- Yoonjin Kwak
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Soo Kyung Nam
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Eun Shin
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Sang-Hoon Ahn
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Hee Eun Lee
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Do Joong Park
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Woo Ho Kim
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Hyung-Ho Kim
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
| | - Hye Seung Lee
- From the Departments of Pathology and Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
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Tani T, Sonoda H, Tani M. Sentinel lymph node navigation surgery for gastric cancer: Does it really benefit the patient? World J Gastroenterol 2016; 22:2894-2899. [PMID: 26973385 PMCID: PMC4779912 DOI: 10.3748/wjg.v22.i10.2894] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
Sentinel lymph node (SLN) navigation surgery is accepted as a standard treatment procedure for malignant melanoma and breast cancer. However, the benefit of reduced lymphadenectomy based on SLN examination remains unclear in cases of gastric cancer. Here, we review previous studies to determine whether SLN navigation surgery is beneficial for gastric cancer patients. Recently, a large-scale prospective study from the Japanese Society of Sentinel Node Navigation Surgery reported that the endoscopic dual tracer method, using a dye and radioisotope for SLN biopsy, was safe and effective when applied to cases of superficial and relatively small gastric cancers. SLN mapping with SLN basin dissection was preferred for early gastric cancer since it is minimally invasive. However, previous studies reported that limited gastrectomy and lymphadenectomy may not improve the patient’s postoperative quality of life (QOL). As a result, the benefit of SLN navigation surgery for gastric cancer patients, in terms of their QOL, is limited. Thus, endoscopic and laparoscopic limited gastrectomy combined with SLN navigation surgery has the potential to become the standard minimally invasive surgery in early gastric cancer.
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Fujimura T, Fushida S, Tsukada T, Kinoshita J, Oyama K, Miyashita T, Takamura H, Kinami S, Ohta T. A new stage of sentinel node navigation surgery in early gastric cancer. Gastric Cancer 2015; 18:210-217. [PMID: 25433568 DOI: 10.1007/s10120-014-0446-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 11/17/2014] [Indexed: 02/07/2023]
Abstract
Sentinel node (SN) navigation surgery is expected to realize organ- and function-preserving surgery with SN mapping, and has been applied in operations for breast cancer and melanoma. But there has been no definite evidence for the SN concept in gastric cancer. A prospective multicenter trial to confirm the SN concept for gastric cancer conducted by the Japan Society of Sentinel Node Navigation Surgery reported that the SN detection rate, sensitivity of positive SNs, and accuracy of nodal status are 97.5% (387/397), 93% (53/57), and 99% (383/387), respectively. A detailed analysis of the trial suggested that strictly the "lymphatic basin concept" rather than the "SN concept" was confirmed in early gastric cancer. The Japan Society of Sentinel Node Navigation Surgery started a new trial of function-preserving gastrectomy with lymphatic basin dissection (LBD) for early gastric cancer without metastasis in SNs on the basis of this promising outcome of the trial. It is supposed that LBD guarantees curability in SN navigation surgery for early gastric cancer. Full-thickness resection or endoscopic submucosal dissection in combination with laparoscopic LBD will soon be a new treatment option for early gastric cancer.
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Affiliation(s)
- Takashi Fujimura
- Gastroenterologic Surgery, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan,
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Zhang X, Soori G, Dobleman TJ, Xiao GG. The application of monoclonal antibodies in cancer diagnosis. Expert Rev Mol Diagn 2013; 14:97-106. [PMID: 24308340 DOI: 10.1586/14737159.2014.866039] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Cancer becomes the second leading cause of death in the world. An effective strategy for early diagnosis of the disease is key to reduce the mortality and morbidity. Development of effective monoclonal antibody (mAb)-based assays or diagnostic imaging techniques for detection of antigens and small molecules that are released from cancerous cells will enhance modern diagnostic medicine of cancer significantly. Although mAb technology is still under development, recent advances in preparation of recombinant antigen and antibody engineering techniques have dramatically enhanced the applications of this technology in cancer diagnosis. Compared with other methods, mAb-based assays may provide spatial, temporal, accurate and quantitative measurement for diagnosis of the disease. This review summarizes the progress of the mAb-based assays in the field of molecular diagnosis of cancer.
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Affiliation(s)
- Xuemei Zhang
- The Medical College of Dalian University, Dalian Economic & Technical Development Zone, Dalian 116622, People's Republic of China, China
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Abstract
Since the concept of early gastric cancer was first described in Japan in 1962, its treatment has evolved from curative surgical resection to endoscopic resection, initially with polypectomy to more recently with endoscopic submucosal dissection. As worldwide experience with these endoscopic techniques evolve and gain acceptance, studies have confirmed its comparable effectiveness with historical surgical outcomes in carefully selected patients. The criteria for endoscopic resection have expanded to offer more patients improved quality of life, avoiding the morbidity and mortality associated with surgery. This article summarizes the evolutional role of endoscopic and surgical therapy in early gastric cancer.
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Affiliation(s)
- Wataru Tamura
- Division of Gastroenterology & Hepatology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA
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Lee HS, Lee HE, Park DJ, Park YS, Kim HH. Precise pathologic examination decreases the false-negative rate of sentinel lymph node biopsy in gastric cancer. Ann Surg Oncol 2011; 19:772-8. [PMID: 21979113 DOI: 10.1245/s10434-011-2106-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2010] [Indexed: 12/27/2022]
Abstract
BACKGROUND Gastric cancer has been identified as a target for sentinel lymph node (SLN) navigational surgery. Although accurate evaluation of SLNs is essential for applying the SLN concept to gastric cancer surgery, there is no standardized pathologic examination protocol for SLNs in gastric cancer. METHODS A total of 231 SLNs from 69 patients with cT1-2, N0 gastric cancer were prospectively examined in this study. During the operation, SLNs were sliced at 2-mm intervals, and frozen sections were analyzed by hematoxylin and eosin (HE) staining in 35 patients or HE staining with rapid immunohistochemistry (IHC) for pancytokeratin (CK) in 34 patients. HE staining and CK IHC were performed postoperatively on each remaining SLN. Non-SLNs were evaluated with 2 levels of HE slides and 1 CK IHC. RESULTS Of 35 patients, metastasis was identified in 10 patients by intraoperative HE staining, and in 12 patients by postoperative HE staining and CK IHC. Two patients had isolated tumor cells (ITCs) detectable by postoperative CK IHC; these patients had non-SLN metastasis. We enrolled another 34 patients and examined 147 SLNs by frozen HE and rapid IHC. In this cohort, 26 patients with negative SLNs by intraoperative examination did not have non-SLN metastasis even after deeper sectioning and CK IHC of non-SLNs (sensitivity, 100%; false negative value, 0%). CONCLUSIONS Our study indicated that precise and detailed intraoperative examination decreases the false-negative rate of SLN biopsy. ITCs in SLNs should not be overlooked, and rapid IHC can be helpful for detecting ITCs intraoperatively.
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Affiliation(s)
- Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
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Lee HE, Park DJ, Kim WH, Kim HH, Lee HS. High FOXP3+ regulatory T-cell density in the sentinel lymph node is associated with downstream non-sentinel lymph-node metastasis in gastric cancer. Br J Cancer 2011; 105:413-9. [PMID: 21730981 PMCID: PMC3172906 DOI: 10.1038/bjc.2011.248] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Background: We aimed to evaluate the immunologic nature of sentinel lymph nodes (SLNs) in gastric cancer patients and to determine whether it can predict non-SLN metastasis. Methods: Sentinel lymph node samples were collected from 64 gastric carcinoma patients who had undergone gastrectomy with SLN biopsy. One representative SLN sample was selected from each patient and was subjected to immunostaining for CD8, CD57, FOXP3, and DC-LAMP. The numbers of marker-positive cells in each sample were counted. The relationships between various immune cell densities and clinicopathologic parameters or metastasis status of SLNs and non-SLNs were sought. Results: High FOXP3+ Treg density of the SLN was found to be significantly associated with the presence of metastasis in either SLNs or non-SLNs. DC-LAMP+ cell density of the SLN was the highest at the isolated tumours cell level, and this decreased along with an increase in tumour metastasis in either SLNs or non-SLNs. Univariate and multivariate logistic regression models revealed that high FOXP3+ Treg density of the SLN was an independently significant predictor of non-SLN metastasis. Conclusions: This study is the first to indicate an important role of SLNs in metastatic dissemination of gastric cancer. Our findings suggest that Tregs could be a new therapeutic target for regulating the metastasis of gastric cancer.
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Affiliation(s)
- H E Lee
- Department of Pathology, Seoul National University Hospital, 28 Yeongon-dong, Jongno-gu, Seoul 110-744, Korea
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Blei F. Literature Watch. Lymphat Res Biol 2010. [DOI: 10.1089/lrb.2010.8402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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