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Zhang Y, Uehara T, Toyota T, Endo R, Matsubara H, Hayashi H. Stannous colloid mixed with indocyanine green as a tracer for sentinel lymph node navigation surgery. Sci Rep 2022; 12:17056. [PMID: 36224309 PMCID: PMC9556759 DOI: 10.1038/s41598-022-21420-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 09/27/2022] [Indexed: 12/30/2022] Open
Abstract
The combined use of a vital dye and radioactive colloid reportedly performs better in detecting sentinel lymph nodes (SLNs) for cancers than the use of either of them alone. However, especially for gastric cancer, two endoscopic procedures are required to administer these two tracers, which burdens the patients and practitioners. Here we propose the use of stannous colloid (SnC) mixed with indocyanine green (ICG) as a new mixed tracer (SnC-ICG); its characteristics were investigated in vivo and in vitro to estimate its usefulness for SLN navigation. The tracers were administered to rats and the accumulation of radioactivity and/or near-infrared fluorescence were evaluated in the regional lymph nodes (LNs) using single positron emission computed tomography and near-infrared fluorescence imaging, respectively. SnC-ICG showed significantly better clearance from the injection site and better migration to primary LNs than the single administration of SnC or ICG aqueous solution. SnC-ICG demonstrated a wide particle size variability, stabilized to 1200-nm upon the addition of albumin in vitro; These properties could contribute to its behavior in vivo. The use of SnC-ICG could contribute better performance to detect SLNs for gastric cancer with less burden on both patients and medical practitioners.
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Affiliation(s)
- Yiting Zhang
- grid.136304.30000 0004 0370 1101Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan
| | - Tomoya Uehara
- grid.136304.30000 0004 0370 1101Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan
| | - Taro Toyota
- grid.26999.3d0000 0001 2151 536XDepartment of Graduate School of Arts and Sciences, The University of Tokyo, Komaba Meguro-ku, Tokyo, Japan
| | - Ryusuke Endo
- grid.136304.30000 0004 0370 1101Department of Medical System Engineering, Graduate School of Engineering, Chiba University, Yayoi-cho, Chiba-shi inage-ku, Chiba, Japan
| | - Hisahiro Matsubara
- grid.136304.30000 0004 0370 1101Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan
| | - Hideki Hayashi
- grid.136304.30000 0004 0370 1101Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan ,grid.136304.30000 0004 0370 1101Center for Frontier Medical Engineering, Chiba University, Chiba, Japan
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Okubo K, Uenosono Y, Arigami T, Matsushita D, Yanagita S, Kijima T, Amatatsu M, Ishigami S, Maemura K, Natsugoe S. Quantitative assessment of fluorescence intensity of ICG in sentinel nodes in early gastric cancer. Gastric Cancer 2018. [PMID: 29516211 DOI: 10.1007/s10120-018-0816-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The sentinel node (SN) detection by dual tracer method using indocyanine green (ICG) and a radioisotope (RI) has been recommended for early gastric cancer. However, institutions are limited due to radioactivity in the RI method. The greatest advantage of the RI method is that it objectively assesses RI uptake as a numerical value. The aim of the present study was to verify the usefulness of ICG fluorescence intensity in SN. METHODS Seventeen patients with early gastric cancer were enrolled in this study. RI uptake by each lymph node was measured using Navigator GPS and fluorescence nodes were identified using the hyper eye medical system (HEMS). Fluorescence intensity in fluorescence nodes was evaluated using ICG intensity imaging software (Mizuho, Japan) of the HEMS. RESULTS The total number of dissected lymph nodes was 227, with an average of 13.3 per patient. The numbers of HN, FN-S, and FN-B were 64, 77, and 34. RI uptake was significantly greater by FN-S than by non-FN-S (P = 0.0016). The median fluorescence intensity value was higher in HN than in non-HN (P < 0.001). A correlation was observed between RI uptake and fluorescence intensity. Dissecting FNs with fluorescence intensity levels of 1-6 resulted in 92.1% dissection of HNs. CONCLUSION It is possible that the evaluation of fluorescence intensity is useful for selected SNs instead of RI tracer. If fluorescence intensity is measurable in surgery, an infrared fluorescence method using ICG may be useful and safe for the detection of SN in early gastric cancer.
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Affiliation(s)
- Keishi Okubo
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
| | - Yoshikazu Uenosono
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.,Molecular Frontier Surgery, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takaaki Arigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.,Molecular Frontier Surgery, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Daisuke Matsushita
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shigehiro Yanagita
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takashi Kijima
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Masahiko Amatatsu
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Sumiya Ishigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Kosei Maemura
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.,Molecular Frontier Surgery, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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Development of a mouse model for the visual and quantitative assessment of lymphatic trafficking and function by in vivo imaging. Sci Rep 2018; 8:5921. [PMID: 29651026 PMCID: PMC5897414 DOI: 10.1038/s41598-018-23693-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 03/15/2018] [Indexed: 12/31/2022] Open
Abstract
Methods for quantitative analysis of long distance lymphatic transport of nanoparticles in live animals are yet to be established. We established a mouse model for analysis of time-dependent transport just beneath the abdominal skin to investigate lymph node-to-lymph node trafficking by in vivo imaging. For this purpose, popliteal lymph nodes (PLNs) as well as efferent and afferent lymphatic vessels, marginal veins, and feeding blood vessels were surgically resected to change the lymphatic flow from footpad injections. Using this model, we observed a novel lymphatic flow from the footpad to the proper axillary lymph node (ALN) via the inguinal lymph node (ILN). This drainage pathway was maintained over 12 weeks. Time-dependent transportation of 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide-labelled liposomes from the footpad to the ILN was successfully quantified by an in vivo imaging system. Moreover, congestion and development of a new collateral lymphatic route was visualised under a lymphedema status. Histological analysis of abdominal skin tissues of this model revealed that PLN resection had no effect on the abdominal lymphatic system between the ILN and ALN. These data indicate that this model might be useful to clarify the mechanisms of lymphedema and study direct transportation of lymph or other substances between lymph nodes.
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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 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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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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Yanagita S, Uenosono Y, Arigami T, Daisuke M, Okubo K, Kijima T, Arima H, Hirata M, Haraguchi N, Hagihara T, Nishizono Y, Ishigami S, Natsugoe S. The clinical usefulness of the intraoperative detection of sentinel lymph node metastases by a rapid RT-PCR system in patients with gastric cancer. Cancer 2015; 122:386-92. [PMID: 26479552 DOI: 10.1002/cncr.29740] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2015] [Revised: 09/15/2015] [Accepted: 09/21/2015] [Indexed: 12/16/2022]
Abstract
BACKGROUND The incidence of pathological lymph node metastases in patients with gastric cancer is 5% to 10%, which means that approximately 90% of patients with gastric cancer may undergo unnecessary lymphadenectomy. The precise intraoperative diagnosis of sentinel lymph node (SN) metastases is essential. The purpose of the current study was to verify the usefulness of a rapid reverse transcriptase-polymerase chain reaction (RT-PCR) system compared with hematoxylin and eosin staining for such diagnoses. METHODS A total of 113 patients with clinical T1-T2 (cT1-T2) gastric cancer, including 73 patients with cT1cN0 disease with a tumor diameter <4 cm, were enrolled in the current study. SNs were identified by a radioisotope method. Carcinoembryonic antigen and cytokeratin 19 were used as markers for RT-PCR and the cutoff values were set using 1701 lymph nodes harvested from 157 patients with gastric cancer. RESULTS SNs were detected in all 113 patients. Sensitivity and accuracy for detection by paraffin section were both 100% in patients with cT1 disease and were 60% and 90%, respectively, in patients with cT2 disease. The sensitivity of RT-PCR for the detection of pathological SN metastases was 92.3%. Furthermore, 11 patients had SN metastases detected only by RT-PCR, and these patients had frequent lymphatic invasion. Hematoxylin and eosin staining detected SN metastases in 6 of 73 patients with cT1cN0 gastric cancer; RT-PCR and frozen section detected SN metastases in 6 and 4 of these patients, respectively. Accordingly, the sensitivity of RT-PCR and frozen section for the detection of those pathological SN metastases were 100% and 66.6%, respectively. CONCLUSIONS The rapid RT-PCR system appears to have clinical usefulness for the intraoperative detection of SN metastases in patients with gastric cancer.
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Affiliation(s)
- Shigehiro Yanagita
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yoshikazu Uenosono
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takaaki Arigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Matsushita Daisuke
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Keishi Okubo
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takashi Kijima
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Hideo Arima
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Munetsugu Hirata
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Naoto Haraguchi
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takahiko Hagihara
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yuka Nishizono
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Sumiya Ishigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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Mitsumori N, Nimura H, Takahashi N, Kawamura M, Aoki H, Shida A, Omura N, Yanaga K. Sentinel lymph node navigation surgery for early stage gastric cancer. World J Gastroenterol 2015. [PMID: 24914329 DOI: 10.3748/wjg.v20.i19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient's quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.
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Affiliation(s)
- Norio Mitsumori
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Hiroshi Nimura
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Naoto Takahashi
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Masahiko Kawamura
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Hiroaki Aoki
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Atsuo Shida
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Nobuo Omura
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Katsuhiko Yanaga
- Norio Mitsumori, Hiroshi Nimura, Naoto Takahashi, Masahiko Kawamura, Hiroaki Aoki, Atsuo Shida, Nobuo Omura, Katsuhiko Yanaga, Department of surgery, the Jikei University School of Medicine, Nisi-shinbashi, Minato-ku, Tokyo 105-8461, Japan
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Kim KH, Kim SH, Kim MC. How much progress has been made in minimally invasive surgery for gastric cancer in Korea?: a viewpoint from Korean prospective clinical trials. Medicine (Baltimore) 2014; 93:e233. [PMID: 25526443 PMCID: PMC4603086 DOI: 10.1097/md.0000000000000233] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Gastric cancer is the most common cancer in Korea. Because the incidence of gastric cancer is still high even with early detection and because of developments in surgical instruments and technological advances, minimally invasive surgery has rapidly become an accepted treatment for gastric cancer in Korea. Many Korean gastric surgeons have contributed to the rapid adaptation of minimally invasive surgery for gastric cancer: not only the Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) group, but also other expert surgeons after the 2000s. Thanks to their vigorous efforts involving active learning, education, workshops, academic communications, and international communications with active laparoscopic gastric surgeons in Korea, numerous results and well-designed large-scale clinical studies have been published or are actively ongoing, thus increasing its wide acceptance as an option for gastric cancer. Now, Korea has become one of the leading countries using minimally invasive surgery for the treatment of gastric cancer. This review article will summarize the current status and issues, as well as the clinical trials that have finished or are ongoing, regarding minimally invasive surgery for gastric cancer in Korea.
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Affiliation(s)
- Ki-Han Kim
- From the Department of Surgery, Dong-A University College of Medicine, Busan, Korea
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9
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Mitsumori N, Nimura H, Takahashi N, Kawamura M, Aoki H, Shida A, Omura N, Yanaga K. Sentinel lymph node navigation surgery for early stage gastric cancer. World J Gastroenterol 2014; 20:5685-93. [PMID: 24914329 PMCID: PMC4024778 DOI: 10.3748/wjg.v20.i19.5685] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 12/28/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient's quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.
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10
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Can MF, Yagci G, Cetiner S. Systematic Review of Studies Investigating Sentinel Node Navigation Surgery and Lymphatic Mapping for Gastric Cancer. J Laparoendosc Adv Surg Tech A 2013; 23:651-62. [DOI: 10.1089/lap.2012.0311] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Mehmet Fatih Can
- Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, Etlik, Ankara, Turkey
| | - Gokhan Yagci
- Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, Etlik, Ankara, Turkey
| | - Sadettin Cetiner
- Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, Etlik, Ankara, Turkey
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Hagihara T, Uenosono Y, Arigami T, Kozono T, Arima H, Yanagita S, Hirata M, Ehi K, Okumura H, Matsumoto M, Uchikado Y, Ishigami S, Natsugoe S. Assessment of sentinel node concept in esophageal cancer based on lymph node micrometastasis. Ann Surg Oncol 2013; 20:3031-7. [PMID: 23584517 DOI: 10.1245/s10434-013-2973-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2012] [Indexed: 12/22/2022]
Abstract
PURPOSE The clinical significance of lymph node micrometastasis remains unclear in patients with esophageal cancer. Therefore, accurate assessment of lymph node status including micrometastasis is important when performing sentinel node (SN) navigation surgery. The purpose of the present study was to investigate the adequacy of SN concept based on lymph node micrometastasis determined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in patients with esophageal cancer. METHODS A total of 57 patients with esophageal cancer who were preoperatively diagnosed as having T1-T2 (cT1-T2) and N0 (cN0) were enrolled. They underwent standard esophagectomy with lymph node dissection. One day before surgery, a total of 3 mCi of 99mTechnetium-tin colloid was endoscopically injected into the submucosa around the tumor. During the operation, radioisotope uptake in the lymph nodes was measured using Navigator GPS. All dissected lymph nodes were investigated by RT-PCR using the double marker of CEA and SCC, hematoxylin-eosin (HE) staining, and IHC. RESULTS Node-positive incidence identified by HE and IHC was 12.3% (7/57) and 19.3% (11/57), respectively. RT-PCR demonstrated micrometastasis in four of 46 patients without nodal metastasis determined by HE staining and IHC. No non-SN metastases were found in 42 patients without micrometastasis identified by IHC and RT-PCR of SN. Accuracy and false negative rates were 100% (57/57) and 0% (0/42), respectively. CONCLUSIONS SN concept might be acceptable in patients with cT1-T2 and cN0 esophageal cancer, even in the presence of micrometastasis identified by IHC and RT-PCR.
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Affiliation(s)
- Takahiko Hagihara
- Department of Digestive Surgery, Breast and Thyroid Surgery, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
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12
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Kusano T, Shiraishi N, Shiroshita H, Etoh T, Inomata M, Kitano S. Poor prognosis of advanced gastric cancer with metastatic suprapancreatic lymph nodes. Ann Surg Oncol 2013; 20:2290-5. [PMID: 23299769 PMCID: PMC3675275 DOI: 10.1245/s10434-012-2839-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Indexed: 12/14/2022]
Abstract
Background Whether gastrectomy with D2 lymphadenectomy improves survival of patients with advanced gastric cancer (AGC) remains controversial. Few studies have described the pathological features of AGC with metastatic suprapancreatic lymph nodes (LN), which are the target of D2 lymphadenectomy. This study therefore aims to clarify the prognosis and clinical pathological features including the number and location of metastatic LN in AGC with metastatic suprapancreatic LN. Methods 406 patients with AGC, who underwent gastrectomy with D2 lymphadenectomy from 1982 to 2007 at Oita University, were reviewed retrospectively with regard to presence or absence of metastatic suprapancreatic LN. The pathological factors associated with AGC with metastatic suprapancreatic LN were examined by univariate and multivariate analysis. Results Of 362 patients with AGC, 78 had suprapancreatic LN metastasis (21.5 %), differing significantly in terms of presence of vascular invasion and having a larger number of metastatic perigastric LN in comparison with only metastatic perigastric LN on univariate analysis. According to multivariate analysis, they were associated with presence of vascular invasion and a large number of total metastatic LN (more than two; N2≤). The overall 5-year survival rate of the AGC with perigastric LN metastasis (station 1–7) group was 37.9 % and of the AGC with suprapancreatic LN metastasis group was 12.8 %. There were significant differences in each group (P < 0.05). Conclusions Patients with AGC with metastatic suprapancreatic LN had a large number of total metastatic LN and poor prognosis, suggesting that it may be a systemic disease.
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Affiliation(s)
- Toru Kusano
- Department of Gastroenterological Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan.
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Yano K, Nimura H, Mitsumori N, Takahashi N, Kashiwagi H, Yanaga K. The efficiency of micrometastasis by sentinel node navigation surgery using indocyanine green and infrared ray laparoscopy system for gastric cancer. Gastric Cancer 2012; 15:287-91. [PMID: 22041868 DOI: 10.1007/s10120-011-0105-6] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Accepted: 09/23/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND The clinical application of sentinel node navigation surgery (SNNS) for patients with gastric cancer requires accurate intraoperative diagnosis of lymph node metastasis. However, the clinical significance of the diagnosis of lymph node micrometastasis for gastric cancer has not been established. In this study, we evaluated lymph nodes dissected during SNNS by immunohistochemistry with anti-cytokeratin antibody (IHC) staining for gastric cancer to investigate the usefulness of SNNS. PATIENTS AND METHODS The subjects were 130 patients with gastric cancer (3,381 lymph nodes) who underwent SNNS with infrared ray observation and lymph node dissection of D1+α or more. The dissected lymph nodes were stained with IHC (CAM 5.2), and the results were compared with intra- and postoperative diagnoses by hematoxylin and eosin (H&E) staining. In addition, the association of metastatic lymph nodes and ICG-positive lymph nodes was examined. RESULTS The number of patients (lymph nodes) with lymph node metastasis by HE and IHC staining was 16 (52 nodes) and 31 (91 nodes), respectively. Fifteen patients (27 nodes) diagnosed with pN0 by HE staining were diagnosed to be metastatic by IHC staining. The tumor depth of these patients was pT1 in ten patients (m, 3; sm, 7) and pT2 in five (mp, 4; ss, 1). Regarding the histological type, three patients were classified as well-differentiated type, while six patients each had moderately and poorly differentiated types. The grade of lymphatic invasion was ly0 in 5, ly1 in 6, and ly2 in 4, respectively. Histological assessment of 27 IHC-positive and HE-negative cells indicated 5 single cells, 16 clusters, and 6 micrometastases. These lymph nodes were all included in the sentinel nodes (SN) identified during surgery. All but one patient (0.8%) were recurrence-free at 2-8 years after surgery (median 74.7 months). The one patient developed anastomotic recurrence 4.5 years after the first operation and died. CONCLUSION Since all 27 lymph nodes in 15 patients with metastasis by IHC staining but not by HE staining were micrometastasis or less and included in the SN, ICG-positive lymphatic basin dissection by SNNS with infrared ray observation seems to be an adequate method of lymph node dissection for gastric cancer.
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Affiliation(s)
- Kentaro Yano
- Department of Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
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Can MF, Yagci G, Cetiner S. Sentinel lymph node biopsy for gastric cancer: Where do we stand? World J Gastrointest Surg 2011; 3:131-7. [PMID: 22007282 PMCID: PMC3192223 DOI: 10.4240/wjgs.v3.i9.131] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2011] [Revised: 08/27/2011] [Accepted: 09/12/2011] [Indexed: 02/06/2023] Open
Abstract
Development of sentinel node navigation surgery (SNNS) and advances in minimally invasive surgical techniques have greatly shaped the modern day approach to gastric cancer surgery. An extensive body of knowledge now exists on this type of clinical application but is principally composed of single institute studies. Certain dye tracers, such as isosulfan blue or patent blue violet, have been widely utilized with a notable amount of success; however, indocyanine green is gaining popularity. The double tracer method, a synchronized use of dye and radio-isotope tracers, appears to be superior to any of the dyes alone. In the meantime, the concepts of infrared ray electronic endoscopy, florescence imaging, nanoparticles and near-infrared technology are emerging as particularly promising alternative techniques. Hematoxylin and eosin staining remains the main method for the detection of sentinel lymph node (SLN) metastases. Several specialized centers have begun to employ immunohistochemical staining for this type of clinical analysis but the equipment costs involving the associated ultra-rapid processing systems is limiting its widespread application. Laparoscopic function-preserving resection of primary tumor from the stomach in conjunction with lymphatic basin dissection navigated by SLN identification represents the current paramount of SNNS for early gastric cancer. Patients with cT3 stage or higher still require standard D2 dissection.
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Affiliation(s)
- Mehmet Fatih Can
- Mehmet Fatih Can, Gokhan Yagci, Sadettin Cetiner, Division of Gastrointestinal Surgery, Department of Surgery, Gulhane School of Medicine, 06018, Etlik, Ankara, Turkey
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15
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Ryu KW, Eom BW, Nam BH, Lee JH, Kook MC, Choi IJ, Kim YW. Is the sentinel node biopsy clinically applicable for limited lymphadenectomy and modified gastric resection in gastric cancer? A meta-analysis of feasibility studies. J Surg Oncol 2011; 104:578-84. [PMID: 21695700 DOI: 10.1002/jso.21995] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2010] [Accepted: 05/23/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND Sentinel node biopsies (SNBs) have been clinically applied in melanoma and breast cancer for limited lymphadenectomy. However, the use of SNB remains controversial in gastric cancer due to unsatisfactory sensitivity and variability. This meta-analysis was performed to determine the sensitivity of SNB in gastric cancer and to identify factors that improve its sensitivity. METHODS Feasibility studies on SNB in gastric cancer were searched for from 2001 to 2009 in Pubmed, Cochrane, and Embase. Forty-six reports, which included 2,684 patients, were found. Estimated sensitivities, detection rates, and negative (NPV), and positive predictive values (PPV) were calculated using a random effects model. Inter-study heterogeneity, meta-regression, and subgroup analysis for sensitivity was performed. RESULTS The estimated sensitivity, detection rate, NPV, and PPV were 87.8%, 97.5%, 91.8%, and 38.0%, respectively, with significant inter-study heterogeneity (P < 0.0001). However, no significant contributor to heterogeneity was identified. By subgroup analysis, sensitivity was found to depend significantly on the number of SNs harvested. CONCLUSIONS SNB in gastric cancer is probably not clinically applicable for limited lymphadenectomy due its unsatisfactory sensitivity and heterogeneity between practicing surgeons. To improve sensitivity, more than four SNs should be harvested, and a tumor specific SNB method should be developed.
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Affiliation(s)
- Keun Won Ryu
- Gastric Cancer Branch, Research Institute & Hospital, National Cancer Center, Gyeonggi-do, Republic of Korea
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16
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Lips DJ, Schutte HW, van der Linden RLA, Dassen AE, Voogd AC, Bosscha K. Sentinel lymph node biopsy to direct treatment in gastric cancer. A systematic review of the literature. Eur J Surg Oncol 2011; 37:655-61. [PMID: 21636243 DOI: 10.1016/j.ejso.2011.05.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2010] [Revised: 03/01/2011] [Accepted: 05/05/2011] [Indexed: 12/23/2022] Open
Abstract
Gastric cancer is one of the main causes of cancer-related deaths around the world. The prevalence of early gastric cancer (EGC) among all gastric cancers of 45-51% in Japan, but only 7-28% in Western countries. The prevalence of EGC is growing partly because of better diagnostics and screening programmes. Possible treatment options for EGC treatment are expanded by the introduction of endoscopic mucosal resection and endoscopic submucosal dissection Therefore, detailed knowledge about nodal metastatic risk is warranted. We performed a systematic review of the literature concerning studies investigating the role of sentinel lymph node biopsy in EGCr and whether there is enough proof to introduce SLN as a part of treatment for EGC in the Netherlands. Several detection substances (dye or radiocolloid) and injection methods (submucosal or subserosal) are investigated. An overall sensitivity percentage of 85.4% was found. In comparison, high and clinically sufficient percentages were observed for specificity (98.2%), negative predictive value (90.7%) and accuracy (94%). Subgroup analyses showed that the combination of dye and radiocolloid detection substances is the best method for sentinel lymph node detection in early gastric cancer. However, the precise method of sentinel lymph node biopsy in EGC has to be determined further. Large, randomized series should be initiated in Europe to address this issue.
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Affiliation(s)
- D J Lips
- Department of Surgery, Jeroen Bosch Hospital, PO Box 90153, Zip code 5200 ME, 's-Hertogenbosch, The Netherlands.
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Hikage M, Gonda K, Takeda M, Kamei T, Kobayashi M, Kumasaka M, Watanabe M, Satomi S, Ohuchi N. Nano-imaging of the lymph network structure with quantum dots. NANOTECHNOLOGY 2010; 21:185103. [PMID: 20388975 DOI: 10.1088/0957-4484/21/18/185103] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Sentinel lymph node diagnosis contributes to operative strategy in cancer surgery. During lymph node metastasis, cancer cells first reach the sentinel lymph node (SLN) via lymph flow. To perform SLN biopsy effectively, it is important that cancer cells are detected with high sensitivity in SLN connected to the tumor site. Here we present a method to visualize a high-risk area in the SLN for lymph node metastasis with a high degree of accuracy. Quantum dots (QDs), bright fluorescent nanoparticles, were endoscopically injected into the gastrointestinal wall of pigs, and their signal was specifically detected in the SLN with a laparoscopic device. Single-particle imaging under a confocal microscope showed that the QDs were distributed heterogeneously in the SLN and that their distribution marked the inflow locus of afferent lymphatic vessels where lymph node metastasis begins. Moreover, we developed a method using cellular marker conjugated QDs that visualizes specific cells in SLNs, suggesting that this method can be applied for the detection of cancer cells in sentinel lymph nodes using tumor-specific-molecular conjugated QDs. These results show that our method might significantly increase the detection rate of cancer metastasis in SLNs.
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Affiliation(s)
- Makoto Hikage
- Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
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18
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Povoski SP, Neff RL, Mojzisik CM, O'Malley DM, Hinkle GH, Hall NC, Murrey DA, Knopp MV, Martin EW. A comprehensive overview of radioguided surgery using gamma detection probe technology. World J Surg Oncol 2009; 7:11. [PMID: 19173715 PMCID: PMC2653072 DOI: 10.1186/1477-7819-7-11] [Citation(s) in RCA: 141] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2008] [Accepted: 01/27/2009] [Indexed: 02/08/2023] Open
Abstract
The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology.
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Affiliation(s)
- Stephen P Povoski
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - Ryan L Neff
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - Cathy M Mojzisik
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - David M O'Malley
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - George H Hinkle
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
- College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA
| | - Nathan C Hall
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - Douglas A Murrey
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - Michael V Knopp
- Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA
| | - Edward W Martin
- Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
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Dong S, Huang G, Liu P, Ma Y, Yan W, Wan L, Zhu C. Efficacy and safety of (32)P-nanocolloid for treatment of distant lymph node metastasis in VX2 tumor-bearing rabbits. Ann Nucl Med 2009; 22:849-58. [PMID: 19142703 DOI: 10.1007/s12149-008-0188-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2008] [Accepted: 06/26/2008] [Indexed: 10/21/2022]
Abstract
BACKGROUND Eradication of micrometastases present in lymph nodes of cancer patients improves their prognosis significantly. Radionuclide therapy possesses the potential to eliminate such metastases. OBJECTIVE This study was performed to evaluate the efficacy and safety of (32)P-nanocolloid therapy in the treatment of distant carcinoma cell metastases in lymph nodes of VX2 tumor-bearing rabbits. METHODS To obtain VX2 tumor micrometastases in right armpit lymph nodes of 12 male New Zealand white rabbits, VX2 tumors were implanted by hypodermal inoculation into the right anterior limb. Animals were randomly divided into therapy (n = 6) and control (n = 6) groups. (32)P-nanocolloid (0.5 mCi), 95% of which was >50 nm in diameter, was administered to the therapy group, and saline was administered to the control group. Injections were given once weekly for 4 weeks. RESULTS 2-Deoxy-2[(18)F]-fluoro-D -glucose positron emission tomography revealed that the number of involved lymph nodes and the maximum standardized uptake value decreased in the (32)P-nanocolloid therapy group as compared with the baseline or saline control group (P < 0.05). The expression of the lymphangiogenesis factors vascular endothelial growth factors (VEGF)-C and VEGF-D by VX2 tumor cells present in lymph nodes was significantly lower in the therapy group as compared with the control group. Additionally, apoptotic VX2 tumor cell death was significantly greater in lymph nodes of the therapy as compared with the control group (P < 0.01). With the exception of a decrease in white blood cells of peripheral blood (P < 0.05), standard laboratory values were unaffected throughout the course of therapy with (32)P-nanocolloid. CONCLUSIONS These findings support treatment with (32)P-nanocolloid as a safe and effective approach for eradication of lymph node micrometastases.
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Affiliation(s)
- Shengxiang Dong
- Department of Nuclear Medicine, Renji Hospital, Medical School of Shanghi Jiaotong University, No. 1630, Rd Dong Fang, 200127 Pudong New District, Shanghai, China
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20
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Lee YJ, Ha WS, Park ST, Choi SK, Hong SC, Park JW. Which biopsy method is more suitable between a basin dissection and pick-up biopsy for sentinel nodes in laparoscopic sentinel-node navigation surgery (LSNNS) for gastric cancer? J Laparoendosc Adv Surg Tech A 2008; 18:357-63. [PMID: 18503367 DOI: 10.1089/lap.2007.0024] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Sentinel-node navigation surgery (SNNS) for breast cancer and melanoma has been accepted as a reasonable oncologic surgery worldwide. On the other hand, in gastric cancers that do metastasize well to the lymph node, the use of SNNS has been approached with care and performed in only limited cases. Some obstacles still have to be overcome, such as the shortcomings of SN tracers and the technical limitations of laparoscopic SN detection. The aims of this study were to determine whether laparoscopic SNNS is possible, and which biopsy method is more suitable for SN tracers, in gastric cancer, preoperatively diagnosed as < or =T2 and with < or =4-cm-sized lesions. MATERIALS AND METHODS Between January 2005 and October 2006, 92 consecutive patients that underwent LSNNS, using a combined indocyanine green and (99m)Tc-labeled tin colloid technique, were prospectively studied. SNs were laparoscopically removed by using two biopsy methods: a basin dissection and pick-up method, with the results of these two SN biopsy methods then compared with the final diagnosis obtained from a permanent section. RESULTS With the pick-up method, SNs were identified in 23 of 42 patients (54.8%); however, with basin dissection, the detection rate was 96% (48 of 50 patients). The average number of SNs detected by the two methods were 2.1 (range, 0-4) and 3.5 (range, 1-7), respectively. The sensitivities of the two methods were 66% (4/6) and 85.7% (12/14), with specificities of 100% (17/17) and 100% (34/34), respectively. CONCLUSION In gastric cancer, it was possible to perform LSNNS. At this moment, we believe the laparoscopic basin dissection technique with a dual-tracer injection, followed by SN detection on the back table, will be a reasonable procedure for gastric cancer, owing to the shortcomings related to the dye and radioisotope, the so-called "stained lymphatic duct only" and "shine-through phenomenon."
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Affiliation(s)
- Young-Joon Lee
- Department of Surgery, Gyeongsang National University Hospital, Jinju, Gyeongsang South Province, Korea. yjlee@
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21
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Yanagita S, Natsugoe S, Uenosono Y, Arigami T, Arima H, Kozono T, Funasako Y, Ehi K, Nakajo A, Ishigami S, Aikou T. Detection of micrometastases in sentinel node navigation surgery for gastric cancer. Surg Oncol 2008; 17:203-10. [PMID: 18539025 DOI: 10.1016/j.suronc.2008.04.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Although lymph node metastasis is one of the important prognostic factors for patients with gastric cancer, the clinical significance of micrometastasis remains controversial. In the 6th edition of the TMN classification, micrometastases were classified as micrometastasis (MM) and isolated tumor cells (ITC) according to its greatest dimension. The accurate diagnosis of micrometastases is required when considering less invasive surgery, especially in early stage of gastric cancer. Since generating useful information about micrometastases by conventional RT-PCR is time-consuming, this procedure is not useful for rapid diagnosis during surgery. Recently some new methods of genetic diagnosis have reduced the amount of time required to obtain information about micrometastases in lymph nodes to 30-40 min. Such methodology can be clinically applied during less invasive surgery. The sentinel node (SN) concept has recently been applied to gastric cancer and SN navigation surgery (SNNS) is ideal for reduction of lymphadenectomy in patients with early gastric cancer. However, we should think about some conditions to establish SN concept for gastric cancer: the particle size of radioisotope, relationship between metastatic area and RI uptake, and the diagnosis of micrometastases by various method such as histological examination, immunostaining and RT-PCR. Here, we described the current status of MM and ITC in the lymph nodes and the SN concept in gastric cancer.
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Affiliation(s)
- Shigehiro Yanagita
- Department of Surgical Oncology, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
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22
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Li C, Kim S, Lai JF, Oh SJ, Hyung WJ, Choi WH, Choi SH, Noh SH. Solitary lymph node metastasis in gastric cancer. J Gastrointest Surg 2008; 12:550-4. [PMID: 17786527 DOI: 10.1007/s11605-007-0285-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2007] [Accepted: 07/29/2007] [Indexed: 02/07/2023]
Abstract
The feasibility and diagnostic reliability of sentinel node (SN) biopsy for gastric cancer are still controversial. We studied the clinicopathological features and localization of solitary lymph node metastasis (SLM) in gastric cancer to provide useful information for use of the SN concept in gastric cancer. From 2000 to 2004, 3,267 patients with gastric cancer underwent D2 radical gastrectomy. The clinicopathological features of 195 patients with histologically proven SLM and the distribution of metastasized nodes were assessed. The incidence of SLM was 6.0% in all cases. Compared with the node-negative patients, significant differences were observed in age, tumor size, depth of invasion, and surgical type. The cumulative 5-year survival rate of patients with SLM was 80.5%, which was significantly lower than 90.2% for node-negative patients (P<0.001). Of patients with SLM, 82.6% had it in the perigastric node area (N1), and the other 17.4% patients had skip metastasis in the N2-N3 nodes. Perigastric nodes were the most common first sites of drainage from the tumor, making them the main targets of the operative SN mapping procedure. Due to the higher than expected incidence of skip metastasis in gastric cancer, D2 lymphadenectomy should be performed until the reliability of SN navigation surgery is validated in multicenter prospective clinical trials.
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Affiliation(s)
- Chen Li
- Department of Surgery, Yonsei University College of Medicine, 134 Shinchon-dong Seodaemun-gu, Seoul, 120-752, South Korea
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Bembenek A, Gretschel S, Schlag PM. Sentinel lymph node biopsy for gastrointestinal cancers. J Surg Oncol 2007; 96:342-52. [PMID: 17726666 DOI: 10.1002/jso.20863] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Sentinel lymph node biopsy (SLNB) in gastrointestinal-(GI)-tract cancer is not yet of clinical relevance. Nevertheless, the results in the upper GI-tract promise to be helpful to individualize the indication for surgical therapy. SLNB in colon cancer still fails to show high validity to predict the nodal status, but may be helpful to clarify the prognostic role of micrometastases/isolated tumor cells. In anal cancer SLNB is able to guide the indication for groin irradiation.
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Affiliation(s)
- A Bembenek
- Department of Surgery and Surgical Oncology, Robert-Rössle-Klinik, Charité Universitätsmedizin Berlin, Campus Buch, Lindenberger, Berlin, Germany
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Yanagita S, Natsugoe S, Uenosono Y, Kozono T, Ehi K, Arigami T, Arima H, Ishigami S, Aikou T. Sentinel node micrometastases have high proliferative potential in gastric cancer. J Surg Res 2007; 145:238-43. [PMID: 17603078 DOI: 10.1016/j.jss.2007.04.037] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2006] [Revised: 03/20/2007] [Accepted: 04/24/2007] [Indexed: 02/07/2023]
Abstract
BACKGROUND The 6th edition of the TNM classification has recently defined "sentinel nodes (SN)," "micrometastasis," and "isolated tumor cells (ITC)." The present study examines the frequency and proliferative activity of such metastases with focus on the SNs of gastric cancer. METHODS We enrolled 133 patients with cT1-2 tumors (cT1: 104, cT2: 29) and mapped SNs. Lymph node metastases were examined by routine histology and by immunohistochemistry with anti-cytokeratin. We used the Ki-67 antibody to detect the primary tumor and lymph node metastases to evaluate proliferative activity. RESULTS The number of patients with SNs metastases and metastatic SNs was 19 and 52, respectively. The frequencies of macrometastasis, micrometastasis, and ITC were 48%, 25%, and 27%, respectively. Ki-67 expression in the tumor closely correlated with lymphatic invasion (P = 0.0001), venous invasion (P < 0.0001), and lymph node metastasis (P < 0.0001). Cells in 96% of macrometastases, 92% of micrometastases, and 29% of ITCs were Ki-67 positive. CONCLUSIONS We showed that micrometastasis and some ITCs in SNs had proliferative activity. We suggest that micrometastasis and ITCs should be removed, especially during SN navigation surgery, until their clinical significance is clarified.
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Affiliation(s)
- Shigehiro Yanagita
- Course of Advanced Therapeutics, Field of Oncology, Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
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de Haas RJ, Wicherts DA, Hobbelink MGG, Borel Rinkes IHM, Schipper MEI, van der Zee JA, van Hillegersberg R. Sentinel lymph node mapping in colon cancer: current status. Ann Surg Oncol 2007; 14:1070-80. [PMID: 17206482 DOI: 10.1245/s10434-006-9258-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND The primary role of sentinel lymph node (SLN) mapping in colon cancer is to increase the accuracy of nodal staging by identifying those lymph nodes with the greatest potential for harbouring metastatic disease. Ultrastaging techniques aim to identify the otherwise undetected metastases. Until now, no consensus exists as to the most optimal procedure in patients with colon cancer. METHODS A systematic literature search on the value of different SLN mapping techniques in patients with colon cancer was performed using the electronic search engine PubMed. Prospective studies published before 1 December 2005 were included and further articles were selected by cross-referencing. The results of different techniques using either blue dye or radiocolloid, were investigated. RESULTS The literature search yielded 17 relevant articles. SLN mapping using blue dye was described in 15 studies. Two studies reported the results of SLN mapping using a combination of blue dye and radiocolloid. The reported results on identification rate varied between 71 and 100%. Accuracy rates were between 78 and 100%, sensitivity rates between 25 and 100% and true upstaging rates between 0 and 26%. The results were not affected by the addition of radiocolloid to blue dye. CONCLUSIONS Sentinel lymph node mapping in patients with colon cancer remains an experimental procedure with varying results. Further evaluation may lead to a standardized technique that offers the potential for significant upstaging of stage II patients. This may have important implications as to tailor adjuvant chemotherapeutic regimens in these patients.
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Affiliation(s)
- Robbert J de Haas
- Department of Surgery, University Medical Center Utrecht, P.O. Box 85500, 3508, GA, Utrecht, The Netherlands
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Tangoku A, Seike J, Nakano K, Nagao T, Honda J, Yoshida T, Yamai H, Matsuoka H, Uyama K, Goto M, Miyoshi T, Morimoto T. Current status of sentinel lymph node navigation surgery in breast and gastrointestinal tract. THE JOURNAL OF MEDICAL INVESTIGATION 2007; 54:1-18. [PMID: 17380009 DOI: 10.2152/jmi.54.1] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Sentinel lymph node biopsy (SLNB) has been developed as a new diagnostic and therapeutic modality in melanoma and breast cancer surgery. The purpose of the SLNB include preventing the operative morbidity and improving the pathologic stage by focusing on fewer lymph nodes using immunocytochemic and molecular technology has almost achieved in breast cancer surgery. The prognostic meaning of immunocytochemically detected micrometastases is also evaluating in the SLN and bone marrow aspirates of women with early-stage breast cancer. SLNB using available techniques have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent because of an aberrant lymphatic drainage outside of the basin exist. At the moment, the available data does not justify reduced extent of lymphadenectomy, but provides strong evidence for an improvement in tumor staging on the basis of SLNB. Two large scale prospective multi-center trials concerning feasibility of gamma-probe and dye detection for gastric cancer are ongoing in Japan. Recent studies have shown favorable results for identification of SLN in esophageal cancer. CT lymphography with endoscopic mucosal injection of iopamidol was applicable for SLN navigation of superficial esophageal cancer. The aim of surgical treatment is complete resection of the tumor-infiltrated organ including the regional lymph nodes. Accurate detection of SLN can achieve a selection of a more sophisticated tailor made approach. The patient can make a individualized choice from a broader spectrum of therapeutic options including endoscopic, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissection. Ultrastaging by detecting micrometastasis at the molecular level and the choice of an adequate treatment improve the postoperative quality of life and survival. However these issues require further investigation.
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Affiliation(s)
- Akira Tangoku
- Department of Oncological and Regenerative Surgery, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
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Gretschel S, Bembenek A, Hünerbein M, Dresel S, Schneider W, Schlag PM. Efficacy of different technical procedures for sentinel lymph node biopsy in gastric cancer staging. Ann Surg Oncol 2007; 14:2028-35. [PMID: 17453300 DOI: 10.1245/s10434-007-9367-y] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2006] [Accepted: 01/12/2007] [Indexed: 12/20/2022]
Abstract
BACKGROUND The clinical impact of sentinel lymph node biopsy (SLNB) in gastric cancer is controversial. We performed a prospective trial to compare different methods: radiocolloid method (RM), dye method (DM), and both methods simultaneously (dual method, or DUM) for reliability and therapeutic consequences. METHODS RM and DM were applied in 35 gastric cancer patients. After endoscopic peritumoral injection of (99m)Tc-colloid and Patent Blue V, the positions of all blue sentinel lymph nodes (SLNs) were recorded, and the SLNs microscopically examined by hematoxylin and eosin, step sections, and immunohistochemistry. RESULTS RM, DM, and DUM identified the SLNs in 34 (97%) of 35 patients. The sensitivity for the prediction of positive lymph node status for RM was 22 (92%) of 24, for DM 16 (66%) of 24, and for DUM 22 (92%) of 24. In 7 of 17 (RM), 5 of 15 (DM), and 7 of 17 (DUM) patients classified as N0 by routine hematoxylin and eosin staining, micrometastases or isolated tumor cells were found in the SLN (upstaging) after focused examination. If only a limited lymph node dissection of the SLN basins would have been performed in patients, residual lymph node metastases were left in 9 of 24 (RM), in 7 of 34 (DM), and in 5 of 24 (DUM) of patients with node-positive disease. CONCLUSIONS Use of RM was superior. DUM did not further increase the sensitivity. A limited lymph node dissection-i.e., lymphatic basin in patients with SLN-positive disease-is associated with a high risk of residual metastases. Patients with negative SLNs may be selected for a limited surgical procedure if they meet certain criteria.
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Affiliation(s)
- Stephan Gretschel
- Department of Surgery and Surgical Oncology, Charité, University Medicine Berlin, Campus Buch, Robert-Rössle-Cancer Hospital, HELIOS Klinikum, Lindenberger Weg 80, Berlin, 13125, Germany
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Arima H, Natsugoe S, Uenosono Y, Arigami T, Ehi K, Yanagita S, Higashi H, Ishigami S, Hokita S, Aikou T. Area of Nodal Metastasis and Radioisotope Uptake in Sentinel Nodes of Upper Gastrointestinal Cancer. J Surg Res 2006; 135:250-4. [PMID: 16863652 DOI: 10.1016/j.jss.2006.06.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2005] [Revised: 05/31/2006] [Accepted: 06/06/2006] [Indexed: 12/19/2022]
Abstract
BACKGROUND Sentinel node navigation surgery has been introduced for the treatment of gastrointestinal tumor. As few studies have examined relationships between metastatic area and radioisotope uptake in sentinel nodes, the present study examined this relationship for gastric and esophageal cancers. METHODS Subjects comprised 43 patients (esophageal cancer, n = 19; gastric cancer, n = 24) with < or =3 lymph node metastases in whom sentinel node mapping with radio-guided methods was performed. Radioisotope uptake was measured after surgery for all dissected lymph nodes. Metastatic area was calculated using the following formula: metastatic area (%) = (area of metastasis/total area of lymph node) x 100. Based on radioisotope uptake, lymph nodes were divided into RI(-) and RI(+) groups. RESULTS In 35 patients, > or =1 metastatic node was present among the sentinel nodes. In 1 patient, no sentinel nodes were detected. No lymph node metastasis was found in sentinel nodes in the remaining seven patients. Lymph nodes were diagnosed as metastatic using preoperative imaging. Mean (+/-SD) metastatic area was significantly higher for RI(-) (68.3 +/- 20.5%) than for RI(+) (15.1 +/- 20.8%; P < 0.0001). Radioisotope uptake was decreased in lymph nodes with >60% metastatic area. CONCLUSIONS The fact that radioisotope uptake is not detectable in some lymph nodes with >60% metastatic area must be considered when planning sentinel node navigation surgery.
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Affiliation(s)
- Hideo Arima
- Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University School of Medical and Dental Science, Kagoshima, Japan.
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Lee JH, Ryu KW, Kim CG, Kim SK, Lee JS, Kook MC, Choi IJ, Kim YW, Chang HJ, Bae JM. Sentinel node biopsy using dye and isotope double tracers in early gastric cancer. Ann Surg Oncol 2006; 13:1168-74. [PMID: 16924376 DOI: 10.1245/s10434-006-9038-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2005] [Accepted: 03/18/2006] [Indexed: 12/31/2022]
Abstract
BACKGROUND The results of sentinel node (SN) biopsy have been improved by the use of dye and isotope double tracers in melanoma and breast cancer. However, the usefulness of this double tracer technique has not been determined in gastric cancer. The aim of this study was to investigate the possibility of improving SN biopsy results by using double tracers in gastric cancer. METHODS Sixty-four gastric adenocarcinoma patients preoperatively diagnosed as cT1N0, were enrolled in the study. (99m)Tc tin colloid was injected by preoperative endoscopy, and lymphoscintigraphy was performed prior to operation. After laparotomy, isosulfan blue was intraoperatively injected using an endoscope. Blue-stained or radioactive nodes were identified and defined as SNs. Gastrectomy with D2 lymphadenectomy was performed in all patients. All dissected lymph nodes were evaluated for metastasis by hematoxylin and eosin staining and immunohistochemistry. RESULTS SN detection rates using dye, isotope, or both tracers were 95.3%, 84.4%, and 96.9%, respectively, and their corresponding sensitivities were 52.9%, 52.9%, and 70.6%. In the pT1 subset, the sensitivity of the double tracer was 87.5%; and in a subset of tumors with diameter <4.5 cm, this was also 87.5%. CONCLUSIONS These findings confirm that SN biopsy results are improved by using double tracers in gastric cancer and suggest that SN biopsy is suitable in cases of small-sized early gastric cancer.
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Affiliation(s)
- Jun Ho Lee
- Research Institute and Hospital, National Cancer Center, 809 Madu1-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, South Korea
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Ichikura T, Chochi K, Sugasawa H, Yaguchi Y, Sakamoto N, Takahata R, Kosuda S, Mochizuki H. Individualized surgery for early gastric cancer guided by sentinel node biopsy. Surgery 2006; 139:501-7. [PMID: 16627059 DOI: 10.1016/j.surg.2005.09.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2005] [Revised: 09/01/2005] [Accepted: 09/10/2005] [Indexed: 12/12/2022]
Abstract
BACKGROUND We have reported that lymphatic mapping using indocyanine green (ICG) solution can be a good tool for identifying sentinel nodes (SNs) in gastric cancer. The purpose of this study was to evaluate individualized operations for gastric cancer guided by SN biopsy and to explore the possibility for more limited operative procedures using SN technology. METHODS SNs were identified by using (99m)Tc-labeled tin colloid and ICG solution in patients with clinically T1N0M0 gastric cancer. When pathologic examination by frozen section revealed metastasis in SNs, we performed a standard D2 gastrectomy. Less extensive lymphadenectomy preserving vagus and pylorus was applied when the SN biopsy was negative. Then, postoperative pathology was analyzed. RESULTS Among the 80 enrolled patients, 7 patients with apparent node metastasis or T2-3 neoplasms and 10 patients with positive metastasis in SNs underwent D2 gastrectomy. Sixty-one patients with negative metastasis in SNs underwent a less extensive, function-preserving gastrectomy. The false-negative rate in sentinel node biopsy was 23% (3/13) for frozen section and 7% (1/14) for postoperative pathology. In 3 patients with a false-negative result, metastasis was found in lymph nodes located at the station where the tracers were distributed. Of the 7 patients in whom metastasis was detected in 2 or more SNs by frozen section, postoperative pathology revealed that 3 patients (43%) belonged to the N2 category. CONCLUSIONS SN biopsy is a useful tool for individualizing the operative procedure for early gastric cancer. Dissecting the lymph node stations only where the tracers are distributed may be a promising procedure for patients with no metastatic SNs.
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Affiliation(s)
- Takashi Ichikura
- Department of Surgery I, National Defense Medical College Hospital, Tokorozawa, Japan.
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Mochiki E, Kuwano H, Kamiyama Y, Aihara R, Nakabayashi T, Katoh H, Asao T, Oriuchi N, Endo K. Sentinel lymph node mapping with technetium-99m colloidal rhenium sulfide in patients with gastric carcinoma. Am J Surg 2006; 191:465-9. [PMID: 16531137 DOI: 10.1016/j.amjsurg.2005.09.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2005] [Revised: 09/21/2005] [Accepted: 09/21/2005] [Indexed: 12/26/2022]
Abstract
BACKGROUND The objective of this study was to determine, with the use of technetium-99m colloidal rhenium sulfide, whether the concept of sentinel lymph nodes (SLNs) is applicable to gastric cancers. METHODS Fifty-nine gastric cancer patients underwent radical gastrectomy and SLN mapping with an intraoperative hand-held gamma probe. After surgery, each transected lymph node was measured for radioisotope (RI) activities by a well-type scintillation counter. RESULTS SLNs were detectable in 57 (96%) of 59 patients. The sensitivity, specificity, and diagnostic accuracy were calculated to be 83.3%, 100%, and 92.9%, respectively. Sensitivity was 100% in the T1 group, 91.6% in the T2 group, and 62.5% in the T3 group. When RI activities were measured with a well-type scintillation counter, every metastatic non-SLN was found to be situated in the same lymphatic basin as the SLNs. CONCLUSION The SLN concept is applicable to patients with early gastric cancer (T1). SLN mapping is suitable for identifying the lymphatic basin in cases of gastric cancer.
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Affiliation(s)
- Erito Mochiki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan.
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Arigami T, Natsugoe S, Uenosono Y, Mataki Y, Ehi K, Higashi H, Arima H, Yanagida S, Ishigami S, Hokita S, Aikou T. Evaluation of sentinel node concept in gastric cancer based on lymph node micrometastasis determined by reverse transcription-polymerase chain reaction. Ann Surg 2006; 243:341-7. [PMID: 16495698 PMCID: PMC1448932 DOI: 10.1097/01.sla.0000201453.65534.f1] [Citation(s) in RCA: 98] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To determine the adequacy of sentinel node (SN) concept based on micrometastasis using immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in gastric cancer. SUMMARY BACKGROUND DATA The SN concept has recently been introduced in gastrointestinal tract cancers. The precise detection of lymph node metastasis including micrometastasis is important for SN navigation surgery. METHODS Sixty-one patients with gastric cancer who were preoperatively diagnosed with T1-T2 (cT1-T2) and N0 (cN0) were enrolled. They underwent standard radical gastrectomy with lymph node dissection. One day before surgery, 4 mCi of (99m)Technetium-tin colloid was endoscopically injected into the submucosa around the tumor. During surgery, radioisotope uptake in the lymph node was measured using Navigator GPS. All dissected lymph nodes were examined by RT-PCR in addition to hematoxylin and eosin staining and IHC. RESULTS Sentinel nodes were identified in all patients (100%). The incidences of metastasis determined by hematoxylin and eosin and IHC were 8.2% (5 of 61) and 13.1% (8 of 61), respectively. Micrometastases undetectable by IHC were identified in 14 patients (23.0%) by RT-PCR. Only 1 patient had micrometastasis detectable by RT-PCR in lymph nodes other than SN, but this patient had a cT2 tumor. In patients with cT1 and cN0 tumors, the false negative and accuracy rates were 0% and 100%, respectively. CONCLUSIONS Although the incidence of micrometastasis detected by RT-PCR was quite high, SN navigation identified such metastasis in all patients except one. Thus, the SN concept was applicable to patients with cT1 and cN0 gastric cancer, even when micrometastasis was detectable by RT-PCR.
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Affiliation(s)
- Takaaki Arigami
- Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
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Arigami T, Natsugoe S, Uenosono Y, Arima H, Mataki Y, Ehi K, Yanagida S, Ishigami S, Hokita S, Aikou T. Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pN0 gastric cancer. Br J Cancer 2005; 93:688-93. [PMID: 16136051 PMCID: PMC2361610 DOI: 10.1038/sj.bjc.6602739] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The monoclonal antibody D2-40 is a specific lymphatic endothelial markers and D2-40 staining have been applicable to evaluate lymphatic invasion in various malignant neoplasms. In the present study, we investigated lymph node micrometastasis determined by immunohistochemistry (IHC) and reverse transcription–polymerase chain reaction (RT–PCR) in all dissected lymph nodes obtained from 80 patients with node-negative gastric cancer, and analysed the relationship between micrometastasis and clinicopathological findings including lymphatic invasion of the resected primary tumour using D2-40 immunohistochemical staining. The incidence of micrometastasis determined by IHC and RT–PCR was 11.3% (nine out of 80) and 31.3% (25 out of 80), respectively. Although haematoxylin–eosin (HE) staining revealed lymphatic invasion in 11.3% (nine out of 80) of patients, D2-40 staining uncovered new invasion in 23.8% (19 out of 80) of patients. In the diagnosis of HE and D2-40 staining, the incidence of micrometastasis was significantly higher in patients with lymphatic invasion than in those without lymphatic invasion (P=0.0150 and P<0.0001, respectively). Micrometastasis correlated more closely with D2-40 than with HE staining. We demonstrated a high incidence of micrometastasis and lymphatic invasion and a correlation between them even in pN0 gastric cancer. When planning less invasive treatment, the presence of such occult cancer cells should be considered.
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Affiliation(s)
- T Arigami
- Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
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Uenosono Y, Natsugoe S, Ehi K, Arigami T, Hokita S, Aikou T. Detection of sentinel nodes and micrometastases using radioisotope navigation and immunohistochemistry in patients with gastric cancer. Br J Surg 2005; 92:886-9. [PMID: 15892159 DOI: 10.1002/bjs.4953] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Patients with early gastric cancer may be treated by minimally invasive surgery. This study investigated the value of sentinel node (SN) navigation surgery, including detection of micrometastases, in patients with clinical (c) T1 and T2 gastric cancer. METHODS The day before surgery (99m)Tc-radiolabelled tin colloid was injected submucosally near the tumour. After resecting the stomach, radioisotope uptake in all dissected lymph nodes was measured during and after surgery. Micrometastasis was detected immunohistochemically using an anticytokeratin antibody. RESULTS SNs were identified in 99 of 104 patients. The rate of identification of SNs in patients with cT1 and cT2 tumours, excluding three technical failures, was 99 and 95 per cent respectively. Lymph node metastases and/or micrometastases were found in 28 patients (15 cT1 and 13 cT2). In the 15 patients with cT1 tumours, at least one SN contained metastasis and/or micrometastasis. For cT1 tumours, the sensitivity and accuracy of detecting SNs were both 100 per cent. Six patients with cT2 tumours had false-negative results. CONCLUSION SN navigation surgery appears to be clinically useful only for cT1 tumours. Based on SN results, the extent of lymphadenectomy may be reduced in patients with early gastric cancer.
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Affiliation(s)
- Y Uenosono
- Department of Surgical Oncology and Digestive Surgery, Kagoshima University School of Medicine, Japan.
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Kitagawa Y, Fujii H, Kumai K, Kubota T, Otani Y, Saikawa Y, Yoshida M, Kubo A, Kitajima M. Recent advances in sentinel node navigation for gastric cancer: a paradigm shift of surgical management. J Surg Oncol 2005; 90:147-51; discussion 151-2. [PMID: 15895450 DOI: 10.1002/jso.20220] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The sentinel node (SN) is defined as the first draining node from the primary lesion and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. In the past 5 years, the validity of SN concept for gastric cancer has been demonstrated by a number of single institutional studies. Using a dual tracer method as the optimal procedure, the radio-guided method allows us to confirm the complete harvest of SNs by gamma probing, while the dye procedure enables us to perform real time observation of the lymphatic vessels. From previous reports, clinically staged T1N0 gastric cancer seems to be a good entity on which to try to change the therapeutic approach based on SN biopsy. At present, two large scale prospective multicenter trials are on-going in Japan. To overcome some remaining issues, such as limited sensitivity of intra-operative diagnosis of metastasis, and technical difficulty in laparoscopic SN detection, further technical and instrumental developments will be required. During this transitional phase, focused lymph node dissection targeted to sentinel lymphatic basins and modified resection of the stomach is an acceptable approach. Although there are several remaining issues, SN navigation should provide a paradigm shift for the surgical management of early gastric cancer in near future.
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Affiliation(s)
- Yuko Kitagawa
- Department of Surgery, Keio University, School of Medicine, Shinanomachi, Tokyo, Japan.
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Owaki T, Yoshinaka H, Ehi K, Kijima Y, Uenosono Y, Shirao K, Nakano S, Natsugoe S, Aikou T. Endoscopic quadrantectomy for breast cancer with sentinel lymph node navigation via a small axillary incision. Breast 2005; 14:57-60. [PMID: 15695082 DOI: 10.1016/j.breast.2004.05.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2003] [Revised: 05/10/2004] [Accepted: 05/12/2004] [Indexed: 02/06/2023] Open
Abstract
A great deal of clinical experience has firmly established the concept of the sentinel lymph node (SN) in breast cancer. SN biopsy allows treatment without axillary lymphadenectomy and has made it possible to perform a surgical intervention via just a small skin incision. In partial resection of the breast (quadrantectomy), we use a double retractor to form a workspace under the skin via a small axillary incision. Resection does not require a large incision even in cases in which the cancer lesion is located in the upper inner or lower inner quadrant of the breast, as the endoscope allows the surgeon to see the workspace formed by the double retractors.
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Affiliation(s)
- T Owaki
- Surgical Center, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, Japan.
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Gretschel S, Bembenek A, Ulmer C, Hünerbein M, Markwardt J, Schneider U, Schlag PM. Prediction of gastric cancer lymph node status by sentinel lymph node biopsy and the Maruyama computer model. Eur J Surg Oncol 2005; 31:393-400. [PMID: 15837046 DOI: 10.1016/j.ejso.2004.11.014] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2004] [Revised: 11/15/2004] [Accepted: 11/23/2004] [Indexed: 12/12/2022] Open
Abstract
AIMS The extent of lymph node dissection in gastric cancer remains controversial. The Maruyama computer model and the sentinel lymph node biopsy (SLNB) are compared for their value to predict the nodal status and lead to stage-adapted surgery. METHODS Thirty four patients with stage I-IV gastric cancer underwent both staging procedures. For SLNB, 15 patients underwent endoscopic, peri-tumoural injection of (99m)Tc-colloid, and 19 patients were injected of Patent blue V. All 'hot' or blue sentinel lymph nodes (SLNs) were separately excised and histopathologically assessed. If the SLN was negative after routine staining by H&E, it was processed completely and reanalysed after immunohistochemistry. RESULTS At least, one SLN was detected by means of SLNB in 33/34 of the patients. The sensitivity to identify a positive nodal status was 22/33 and the specificity/positive predictive value was 10/10 and 22/22. Additional micrometastases or isolated tumour cells in the SLN led to 'upstaging' of 5/15, initially classified as nodal negative by H&E-staining. Using the Maruyama computer model, a sensitivity of 22/23 for the correct prediction of the lymph node involvement was associated with a specificity of 2/10 and a positive predictive value of 22/30. CONCLUSIONS The clinical impact of the Maruyama computer model is limited due to low specificity and a low positive predictive value, rendering the method less useful as an indicator for individualised surgery.
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Affiliation(s)
- S Gretschel
- Department of Surgery and Surgical Oncology, Universitätsmedizin Berlin, Charité Campus Berlin-Buch, Robert-Rössle Hospital, Lindenberger Weg 80, D-13122 Berlin, Germany
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Schlag PM, Bembenek A, Schulze T. Sentinel node biopsy in gastrointestinal-tract cancer. Eur J Cancer 2004; 40:2022-32. [PMID: 15341974 DOI: 10.1016/j.ejca.2004.04.033] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2004] [Accepted: 04/22/2004] [Indexed: 10/26/2022]
Abstract
Forty three years after Gould's first description of the sentinel lymph node (SN) technique in malignant tumours of the parotid, sentinel lymph node biopsy (SLNB) has become an invaluable tool for the treatment of solid tumours. In some tumour types, it has been shown to reliably reflect the lymph node (LN) status of the tumour-draining LN basin. In melanoma and breast cancers, it has become a widely accepted element in the routine surgical management of these malignant diseases. In gastrointestinal tumours, the technique is currently under intense investigation. First reports on its application in other solid tumours like non-small cell lung cancer, thyroid carcinoma, oropharyngeal carcinoma, vulvar carcinoma, and Merkel Cell carcinoma of the skin were published more recently. In the following review, we will give a synopsis of the fundamentals of the SN concept and will then proceed to an overview of recent advances of SLNB in gastrointestinal cancers.
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Affiliation(s)
- P M Schlag
- Klinik für Chirurgie und Chirurgische Onkologie, Universitätsmedizin Berlin, Robert-Rössle-Klinik Berlin, Charité, Campus Buch, Lidenberger Weg 80, 13125, Germany.
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Burian M, Stein HJ, Sendler A, Feith M, Siewert JR. [Sentinel lymph node mapping in gastric and esophageal carcinomas]. Chirurg 2004; 75:756-60. [PMID: 15278234 DOI: 10.1007/s00104-004-0909-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
During the last 5 years, the concept of sentinel lymph nodes has been investigated in a variety of solid tumors. Despite the multidirectional and complex lymphatic drainage of the stomach, early gastric cancer has been shown to be a suitable model for sentinel lymph node mapping. In contrast, sentinel lymph node mapping of esophageal cancer is compromised by the anatomic location of the esophagus and its lymphatic drainage in the closed space of the mediastinum. The technique and clinical application of sentinel lymph node mapping thus differ between esophageal and gastric cancer. Reliable detection of sentinel lymph nodes in the mediastinum requires radioisotope labelling, while blue dye and radioisotope labelling are both feasible for gastric cancer. In patients with early gastric cancer, laparoscopic resection with sentinel node negative status is already under investigation in clinical trials. In esophageal cancer, sentinel node mapping is still considered an experimental technique. Preliminary data, however, indicate that it may be reliable and feasible in patients with early adenocarcinoma of the distal esophagus.
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Affiliation(s)
- M Burian
- Chirurgische Klinik und Poliklinik, Klinikum Rechts der Isar, Technische Universität München.
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Higashi H, Natsugoe S, Uenosono Y, Ehi K, Arigami T, Nakabeppu Y, Nakajo M, Aikou T. Particle size of tin and phytate colloid in sentinel node identification1. J Surg Res 2004; 121:1-4. [PMID: 15313367 DOI: 10.1016/j.jss.2004.02.011] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2003] [Indexed: 11/24/2022]
Abstract
BACKGROUND Sentinel node navigation surgery (SNNS) has recently been introduced for various types of carcinoma. Numerous radioisotopes are used as tracers for SNNS. However, few reports have examined particle sizes of isotope colloids used in SNNS. MATERIALS AND METHODS Tin and phytate colloids were used in the present study. Isotonic sodium chloride and tin solutions were mixed ratios of 1:4, 1:2, 1:1, 2:1, and 4:1. Calcium solution and Tc-phytate were mixed at ratios of 1:4, 1:2, 1:1, 2:1 and 4:1. Particle size was measured using a Coulter Model N4SD Sub-micron Particle Analyzer. RESULTS When isotonic sodium chloride and tin solutions were mixed at ratios of 1:4, 1:2, 1:1, 2:1, and 4:1, particle size was 47 +/- 9, 96 +/- 10, 712 +/- 83, 925 +/- 66 and 1079 +/- 132 nm, respectively. As the ratio of tin solution decreased, colloid particle size increased. Particle size of phytate colloid varied from 174 +/- 39 nm to 1222 +/- 283 nm, according to calcium concentration. Phytate colloid particle size became larger as the ratio of phytate solution decreased. CONCLUSIONS We ascertained that the particle size of tin and phytate colloids is controllable by manipulating the conditions under which the colloids form. These results will offer useful information when SNNS is performed.
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Affiliation(s)
- Hiroshi Higashi
- First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
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Sato K, Krag D, Tamaki K, Anzai M, Tsuda H, Kosuda S, Kusano S, Hiraide H, Mochizuki H. Optimal particle size of radiocolloid for sentinel node identification in breast cancer — Electron microscopic study and clinical comparison. Breast Cancer 2004; 11:256-63; discussion 264-6. [PMID: 15550844 DOI: 10.1007/bf02984546] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Sentinel node (SN) biopsy using a radiotracer is easy to learn, reproducible, and performed by the majority of breast cancer surgeons. However, this technique raises the question: what is the optimal particle size of colloid? METHODS Patients were injected with conventional tin colloid (median particle diameter: 700 nm) and the predominant particle size of radiocolloid retained in the SN was measured using electron microscopy. This showed a narrow distribution of colloidal size (100-150 nm). Patients were then injected with modified tin colloid having a median particle size of 100 nm. A clinical comparison was performed between conventional particle size or reduced particle size tin colloid and the SN biopsy success rate, the number of SNs, and the colloidal uptake in SNs. RESULTS A total of 118 patients were injected with the conventional tin colloid (group I) and 124 patients with the smaller particle colloid (group II). The identification rate and the number of SN in both groups were almost equal, and the patients with low-uptake SNs were not significantly less in group I(p = 0.55). However, in the subgroup of patients 60 years of age or more, group II had significantly more SNs than group I(1.4 vs 1.9; p = 0.03) and low-uptake SNs were significantly less common than in group I(p = 0.02). CONCLUSIONS The improvement of colloidal uptake in SNs using the smaller particle size tin colloid was confirmed, and this impact was statistically significant in the older population.
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Affiliation(s)
- Kazuhiko Sato
- Breast Oncology Center, Dana-Farber Cancer Institute 44 Binney Street, Boston, Massachusetts 02115, USA.
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Fujii H, Kitagawa Y, Kitajima M, Kubo A. Sentinel nodes of malignancies originating in the alimentary tract. Ann Nucl Med 2004; 18:1-12. [PMID: 15072178 DOI: 10.1007/bf02985608] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The feasibility of the sentinel node concept for malignancies originating in the alimentary tract is attracting much interest among researchers in the field of gastrointestinal oncology. We have tested more than 350 such cases and obtained favorable and promising initial results. The detectability of sentinel nodes using endoscopically injected Tc-99m tin colloid for these tumors exceeded 90%. Although the false negative ratio was not so low (approximately 10%), most of these cases had an inaccurate preoperative evaluation of mural invasion and/or a technically unfavorable injection. When the indication is restricted to patients with early-stage disease, and when the radioactive colloid is properly administered, sentinel node navigation therapy would be applicable for gastrointestinal malignancies. To achieve successful sentinel node navigation surgery it is essential to accurately identify sentinel nodes, and lymphoscintigraphy is a very useful test to confirm the location of sentinel nodes preoperatively. However, image processing is required for lymphoscintigrams because the original image depicts only high activity at the injection site and faint radioactivity in the sentinel nodes. We have clearly imaged the silhouette of the body using Compton scattered photons, and have also proposed several methods to improve the contrast between the injection sites and sentinel nodes. Many sentinel nodes can be clearly visualized by subtraction of the background activity with heterogeneous distribution. The development of the portable gamma camera, enabling intraoperative imaging, also contributes to less invasive biopsy of sentinel nodes. We have obtained promising initial results using a portable imaging device with semiconductor detectors. These promising results suggest that sentinel node navigation therapy including radiotherapy will be a new therapy for early-stage gastrointestinal malignancies in the near future, with nuclear medicine contributing to the establishment of new, less invasive therapies for gastrointestinal cancer.
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Affiliation(s)
- Hirofumi Fujii
- Department of Radiology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
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