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ArmTan K, Kim YM. Indocyanine green and near-infrared fluorescence-guided surgery for gastric cancer: a narrative review. JOURNAL OF MINIMALLY INVASIVE SURGERY 2024; 27:185-197. [PMID: 39675751 DOI: 10.7602/jmis.2024.27.4.185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 12/03/2024] [Accepted: 12/04/2024] [Indexed: 12/17/2024]
Abstract
In recent years, indocyanine green (ICG) and near-infrared (NIR) fluorescence-guided surgery has become a versatile and well-researched tool for gastric cancer treatment. Our narrative review aims to explore the applications, benefits, and challenges that are associated with this technique. Initially used to detect sentinel lymph nodes in early gastric cancer, its scope has broadened to include several clinical applications. Its most notable advantages are the ability to guide standard lymphadenectomy, intraoperatively localize tumors and define tumor margins. Despite these advantages, there are still ongoing discussions regarding its accuracy, lack of standardized administration, and oncologic safety in sentinel node navigation surgery. The limited tumor specificity of ICG has been especially put into question, hindering its ability to accurately differentiate between malignant and healthy tissue. With ongoing innovations and its integration into newer endoscopic and robotic systems, ICG-NIR fluorescence imaging shows promise in becoming a standard tool in the surgical treatment of gastric cancer.
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Affiliation(s)
- Kristoff ArmTan
- Division of Gastrointestinal Surgery, Department of Surgery, Severance Hospital, Seoul, Korea
- Department of Surgery, Chong Hua Hospital, Cebu, Philippines
| | - Yoo Min Kim
- Division of Gastrointestinal Surgery, Department of Surgery, Severance Hospital, Seoul, Korea
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2
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Togami S, Tanimoto A, Yanazume S, Tokunaga H, Nagai T, Watanabe M, Yahata H, Asanoma K, Yamamoto H, Tanaka T, Ohmichi M, Yamada T, Todo Y, Yamada R, Kato H, Yamagami W, Masuda K, Kawaida M, Niikura H, Moriya T, Kobayashi H. Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: A multicenter prospective study. Gynecol Oncol 2023; 170:70-76. [PMID: 36638744 DOI: 10.1016/j.ygyno.2022.12.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/20/2022] [Accepted: 12/26/2022] [Indexed: 01/13/2023]
Abstract
OBJECTIVE This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-μm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.
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Affiliation(s)
- Shinichi Togami
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Akihide Tanimoto
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
| | - Shintaro Yanazume
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Hideki Tokunaga
- Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Miyagi, Japan
| | - Tomoyuki Nagai
- Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Miyagi, Japan
| | - Mika Watanabe
- Department of Pathology, Tohoku Kosai Hospital, Sendai, Japan
| | - Hideaki Yahata
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazuo Asanoma
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hidetaka Yamamoto
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomohito Tanaka
- Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Masahide Ohmichi
- Department of Obstetrics and Gynecology, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Takashi Yamada
- Department of Pathology, Osaka Medical and Pharmaceutical University, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
| | - Yukiharu Todo
- Division of Gynecologic Oncology, National Hospital Organization, Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo 003-0804, Japan
| | - Ryutaro Yamada
- Division of Gynecologic Oncology, National Hospital Organization, Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo 003-0804, Japan
| | - Hidenori Kato
- Division of Gynecologic Oncology, National Hospital Organization, Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo 003-0804, Japan
| | - Wataru Yamagami
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Kenta Masuda
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Miho Kawaida
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Hitoshi Niikura
- Department of Obstetrics and Gynecology, National Hospital Organization Sendai Medical Center, Miyagi, Japan
| | - Takuya Moriya
- Department of Pathology, Kawasaki Medical School, Okayama, Japan
| | - Hiroaki Kobayashi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
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Belia F, Biondi A, Agnes A, Santocchi P, Laurino A, Lorenzon L, Pezzuto R, Tirelli F, Ferri L, D’Ugo D, Persiani R. The Use of Indocyanine Green (ICG) and Near-Infrared (NIR) Fluorescence-Guided Imaging in Gastric Cancer Surgery: A Narrative Review. Front Surg 2022; 9:880773. [PMID: 35836598 PMCID: PMC9273882 DOI: 10.3389/fsurg.2022.880773] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 06/08/2022] [Indexed: 11/13/2022] Open
Abstract
Near-infrared fluorescence imaging with indocyanine green is an emerging technology gaining clinical relevance in the field of oncosurgery. In recent decades, it has also been applied in gastric cancer surgery, spreading among surgeons thanks to the diffusion of minimally invasive approaches and the related development of new optic tools. Its most relevant uses in gastric cancer surgery are sentinel node navigation surgery, lymph node mapping during lymphadenectomy, assessment of vascular anatomy, and assessment of anastomotic perfusion. There is still debate regarding the most effective application, but with relatively no collateral effects and without compromising the operative time, indocyanine green fluorescence imaging carved out a role for itself in gastric resections. This review aims to summarize the current indications and evidence for the use of this tool, including the relevant practical details such as dosages and times of administration.
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Affiliation(s)
| | - Alberto Biondi
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Correspondence: Alberto Biondi
| | - Annamaria Agnes
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | | | - Laura Lorenzon
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberto Pezzuto
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Flavio Tirelli
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Domenico D’Ugo
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberto Persiani
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Togami S, Fukuda M, Yanazume S, Kamio M, Kobayashi H. A preliminary study on the detection of lymph node metastasis in cervical cancer using a quantitative RT-PCR assay. Jpn J Clin Oncol 2022; 52:475-478. [PMID: 35134177 DOI: 10.1093/jjco/hyac006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 01/10/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE This preliminary study aimed to assess the detection accuracy of sentinel lymph node metastasis in cervical cancer using quantitative reverse transcriptase-polymerase chain reaction. METHODS We collected cervical cancer tissues and 70 pelvic lymph node samples from patients with cervical cancer. The quantitative reverse transcriptase-polymerase chain reaction assay was performed to investigate the expression of cytokeratin 19 mRNA in cervical cancer tissues and determine the cutoff value of cytokeratin 19 mRNA between the non-metastatic and metastatic lymph nodes. RESULTS The expression of cytokeratin 19 mRNA in cancer tissues was detected in all (71/71) the tumours, with a median copy number of 7.56 × 105/μl of RNA by quantitative reverse transcriptase-polymerase chain reaction. Sixteen lymph nodes were diagnosed as positive by pathological examination. The median copy numbers of cytokeratin 19 mRNA for positive and negative lymph nodes were 43.3 × 104/μl and 121.1/μl, respectively. The expression of cytokeratin 19 mRNA in pathologically positive lymph nodes was higher than that in the negative lymph nodes (P < 0.0001) by quantitative reverse transcriptase-polymerase chain reaction analysis. Using a receiver operating characteristic plot, the maximum sensitivity (100%) and specificity (94.4%) were obtained when the cutoff value was set at 1169 copies/μl. CONCLUSIONS After setting the cutoff value at 1169 copies/μl, a quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA showed high accuracy in detecting lymph node metastasis in cervical cancer. We believe that the quantitative reverse transcriptase-polymerase chain reaction assay using cytokeratin 19 mRNA may be acceptable for lymph node metastasis detection in patients with cervical cancer.
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Affiliation(s)
- Shinichi Togami
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Mika Fukuda
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Shintaro Yanazume
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Masaki Kamio
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Hiroaki Kobayashi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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Huang Y, Pan M, Deng Z, Ji Y, Chen B. How useful is sentinel lymph node biopsy for the status of lymph node metastasis in cT1N0M0 gastric cancer? A systematic review and meta-analysis. Updates Surg 2021; 73:1275-1284. [PMID: 33723712 DOI: 10.1007/s13304-021-01026-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 03/11/2021] [Indexed: 11/25/2022]
Abstract
Sentinel lymph node biopsy (SLNB) is intriguing because it is expected to further expand the indication of endoscopic resection (ER) for cT1N0M0 gastric cancer and as an additional operation for post-ER gastric cancer. The aim of our study was to perform a systematic review and meta-analysis on the feasibility and diagnostic value of SLNB technique in patients with cT1N0M0 gastric cancer. Eligible studies were systematically searched in PubMed, Embase, and Cochrane Library databases from inception to April 2020. A random-effect model was used to pool the data, and subgroup analysis was used to explain the heterogeneities. A total of 22 clinical studies (1993 patients with cT1N0M0 gastric cancer) were included. The pooled SLN identification rate, sensitivity, specificity, and diagnostic odds ratio with 95% confidence intervals were 0.99 (0.99-1.00), 0.92 (0.88-0.95), 1.00 (1.00-1.00), and 832.8 (395.5-1753.6), respectively. The summary receiver operator characteristic displayed a test accuracy of 99.3%. Subgroup analysis found an improved SLN sensitivity for studies with the mean number of SLNs > 4 and studies stained with a combination of hematoxylin-eosin with immunohistochemistry (HE + IHC). Further, studies using the basin dissection were associated with a higher SLN identification rate. The current meta-analysis provides data that favors the use of SLNB for predicting the status of lymph node metastasis in patients with cT1N0M0 gastric cancer. However, establishing standard procedure and suitable criteria for further application and optimization of SLNB is urgently needed.
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Affiliation(s)
- Yuqiang Huang
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China.,Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Mengting Pan
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Zhiwei Deng
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China
| | - Yufei Ji
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Bo Chen
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China. .,Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China. .,Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361001, China.
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6
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Friedel D, Zhang X, Stavropoulos SN. Burgeoning study of sentinel-node analysis on management of early gastric cancer after endoscopic submucosal dissection. World J Gastrointest Endosc 2020; 12:119-127. [PMID: 32341748 PMCID: PMC7177205 DOI: 10.4253/wjge.v12.i4.119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 01/11/2020] [Accepted: 03/01/2020] [Indexed: 02/06/2023] Open
Abstract
Endoscopic submucosal dissection (ESD) represents an organ-preserving alternative to surgical resection of early gastric cancer. However, even with ESD yielding en-bloc resection specimens, there are concerns regarding tumor spread such as with larger lesions, ulcerated lesions, undifferentiated pathology and submucosal invasion. Sentinel node navigational surgery (SNNS) when combined with ESD offers a minimally invasive alternative to the traditional extended gastrectomy and lymphadenectomy if lack of lymph node spread can be confirmed. This would have a clear advantage in terms of potential complications and quality of life. However, SNNS, though useful in other malignancies such as breast cancer and melanoma, may not have a sufficient sensitivity for malignancy and negative predictive value in EGC to justify this as standard practice after ESD. The results of SNNS may improve with greater standardization and more involved dissection, technological innovations and more experience and validation such that the paradigm for post-ESD resection of EGC may change and include SNNS.
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Affiliation(s)
- David Friedel
- Department of Gastroenterology, New York University Winthrop Hospital, Mineola, NY 11501, United States
| | - Xiaocen Zhang
- Department of Internal Medicine, Mount Sinai St. Luke’s West Hospital Center, New York, NY 10019, United States
| | - Stavros Nicholas Stavropoulos
- Department of Gastroenterology, Hepatology and Nutrition, NYU-Winthrop University Hospital, Mineola, NY 11501, United States
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7
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Sentinel lymph node detection for gastric cancer: Promise or pitfall? Surg Oncol 2019; 33:1-6. [PMID: 31885358 DOI: 10.1016/j.suronc.2019.12.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 11/24/2019] [Accepted: 12/18/2019] [Indexed: 12/15/2022]
Abstract
At present, optimal surgery for gastric cancer is still under debate, especially the extent of lymph node dissection. Gastrectomy with D1/D2 lymphadenectomy is standard treatment for resectable advanced gastric cancer. However, in early gastric cancer without lymph node metastasis, gastrectomy with D1/D2 lymphadenectomy may not be unnecessary, which could increases morbidity and mortality and reduces the quality of life (QOL). Therefore, the concept of sentinel lymph node could be applied in gastric cancer. But due to the complexity of gastric lymphatic drainage, there are still many issues under debate, such as suitable tracers, the method of mapping and collecting and the oncologic safety of sentinel node navigation surgery (SNNS). In addition, skip metastasis and unreliability of intraoperative pathological diagnosis are two main reasons for false negative cases. In this review, we summarize the current status and controversy of sentinel lymph node detection in gastric cancer, attempting to help with practical application. Further, we hold opinion that we should be cautious about performing sentinel lymph node detection in gastric cancer before an accurate and effective method occurs.
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8
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Togami S, Kawamura T, Fukuda M, Yanazume S, Kamio M, Kobayashi H. Quantitative RT-PCR Assay for Detecting Lymph Node Metastasis in Endometrial Cancer: A Preliminary Study. Oncology 2018; 96:179-182. [PMID: 30428472 DOI: 10.1159/000493485] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 09/03/2018] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The detection accuracy of sentinel lymph node (SLN) metastasis by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for endometrial cancer (EC) remains unclear and was assessed in this preliminary study. METHODS We studied primary cancer tissues and pelvic lymph nodes (PLN) from 105 patients with EC. qRT-PCR assay was performed to determine the copy numbers of CK19 mRNA in EC tissues, and negative and positive LN samples. Further, qRT-PCR results were compared with pathological findings. RESULTS CK19 mRNA expression was detected in 98% (104/106) of the tumors, with a median copy number of 3.0 × 105/μL. Twelve LN were diagnosed as positive by pathological examination. The median copy number of CK19 mRNA for positive and negative LN was 8.1 × 104/μL and 90.4/µL, respectively. CK19 mRNA expression was higher in pathologically positive LN than in pathologically negative LN (p < 0.01); the pathological and qRT-PCR findings showed no discrepancy. When the cutoff value was set at 4,500 copies/µL, qRT-PCR assay using CK19 mRNA exhibited high sensitivity and specificity. CONCLUSIONS Our results demonstrated that qRT-PCR assay, using CK19 mRNA, exhibits a high accuracy for detecting LN metastasis in EC and represents a useful alternative to conventional pathological diagnosis of EC.
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Affiliation(s)
- Shinichi Togami
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan,
| | - Toshihiko Kawamura
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Mika Fukuda
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Shintaro Yanazume
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Masaki Kamio
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Hiroaki Kobayashi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
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Skubleny D, Dang JT, Skulsky S, Switzer N, Tian C, Shi X, de Gara C, Birch DW, Karmali S. Diagnostic evaluation of sentinel lymph node biopsy using indocyanine green and infrared or fluorescent imaging in gastric cancer: a systematic review and meta-analysis. Surg Endosc 2018; 32:2620-2631. [PMID: 29484554 DOI: 10.1007/s00464-018-6100-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 02/07/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Sentinel node navigation surgery (SNNS) for gastric cancer using infrared visualization of indocyanine green (ICG) is intriguing because it may limit operative morbidity. We are the first to systematically review and perform meta-analysis on the diagnostic utility of ICG and infrared electronic endoscopy (IREE) or near infrared fluorescent imaging (NIFI) for SNNS exclusively in gastric cancer. METHODS A search of electronic databases MEDLINE, EMBASE, SCOPUS, Web of Science, and the Cochrane Library using search terms "gastric/stomach" AND "tumor/carcinoma/cancer/neoplasm/adenocarcinoma/malignancy" AND "indocyanine green" was completed in May 2017. Articles were selected by two independent reviewers based on the following major inclusion criteria: (1) diagnostic accuracy study design; (2) indocyanine green was injected at tumor site; (3) IREE or NIFI was used for intraoperative visualization. 327 titles or abstracts were screened. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS Ten full text studies were selected. 643 patients were identified with the majority of patients possessing T1 tumors (79.8%). Pooled identification rate, diagnostic odds ratio, sensitivity, and specificity were 0.99 (0.97-1.0), 380.0 (68.71-2101), 0.87 (0.80-0.93), and 1.00 (0.99-1.00), respectively. The summary receiver operator characteristic for ICG + IREE/NIFI demonstrated a test accuracy of 98.3%. Subgroup analysis found improved test performance for studies with low-risk QUADAS-2 scores, studies published after 2010 and submucosal ICG injection. IREE had improved diagnostic odds ratio, sensitivity, and identification rate compared to NIFI. Heterogeneity among studies ranged from low (I2 < 25%) to high (I2 > 75%). CONCLUSIONS We found encouraging results regarding the accuracy, diagnostic odds ratio, and specificity of the test. The sensitivity was not optimal but may be improved by a strict protocol to augment the technique. Given the number and heterogeneity of studies, our results must be viewed with caution.
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Affiliation(s)
- Daniel Skubleny
- Department of Surgery, Faculty of Medicine and Dentistry, 2D, Walter C Mackenzie Health Sciences Centre, University of Alberta, 840-112 Street, Edmonton, T6G 2B7, Canada.
| | - Jerry T Dang
- Department of Surgery, Faculty of Medicine and Dentistry, 2D, Walter C Mackenzie Health Sciences Centre, University of Alberta, 840-112 Street, Edmonton, T6G 2B7, Canada
| | - Samuel Skulsky
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Noah Switzer
- Department of Surgery, Faculty of Medicine and Dentistry, 2D, Walter C Mackenzie Health Sciences Centre, University of Alberta, 840-112 Street, Edmonton, T6G 2B7, Canada
| | - Chunhong Tian
- Department of Surgery, Faculty of Medicine and Dentistry, 2D, Walter C Mackenzie Health Sciences Centre, University of Alberta, 840-112 Street, Edmonton, T6G 2B7, Canada
| | - Xinzhe Shi
- Centre for the Advancement of Minimally Invasive Surgery (CAMIS), Royal Alexandra Hospital, Edmonton, Canada
| | - Christopher de Gara
- Department of Surgery, Faculty of Medicine and Dentistry, 2D, Walter C Mackenzie Health Sciences Centre, University of Alberta, 840-112 Street, Edmonton, T6G 2B7, Canada.,Centre for the Advancement of Minimally Invasive Surgery (CAMIS), Royal Alexandra Hospital, Edmonton, Canada
| | - Daniel W Birch
- Department of Surgery, Faculty of Medicine and Dentistry, 2D, Walter C Mackenzie Health Sciences Centre, University of Alberta, 840-112 Street, Edmonton, T6G 2B7, Canada.,Centre for the Advancement of Minimally Invasive Surgery (CAMIS), Royal Alexandra Hospital, Edmonton, Canada
| | - Shahzeer Karmali
- Department of Surgery, Faculty of Medicine and Dentistry, 2D, Walter C Mackenzie Health Sciences Centre, University of Alberta, 840-112 Street, Edmonton, T6G 2B7, Canada.,Centre for the Advancement of Minimally Invasive Surgery (CAMIS), Royal Alexandra Hospital, Edmonton, Canada
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10
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Natsugoe S, Arigami T, Uenosono Y, Yanagita S. Novel surgical approach based on the sentinel node concept in patients with early gastric cancer. Ann Gastroenterol Surg 2017; 1:180-185. [PMID: 29863111 PMCID: PMC5881309 DOI: 10.1002/ags3.12027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 06/23/2017] [Indexed: 12/16/2022] Open
Abstract
Recent prospective multicenter trials have demonstrated the clinical safety and efficacy of sentinel node navigation surgery (SNNS) in patients with early gastric cancer. Further, development of an intraoperative imaging system and an indocyanine green fluorescence imaging approach has been attracting attention as a novel tool for detection of the sentinel node (SN). The greatest advantage of an in vivo imaging system is that it visualizes SN and afferent lymphatic vessels from the primary tumor site more clearly than the conventional dye approach. Besides visualization of the SN, it is also essential to accurately assess the presence or absence of lymph node metastasis in the intraoperative management of SNNS. However, the clinical significance of lymph node micrometastasis (LNM) in patients with gastric cancer remains controversial. Reverse transcription‐polymerase chain reaction (RT‐PCR) is one of the representative assays used to identify LNM. A rapid RT‐PCR assay that completes the detection of LNM within approximately 40 minutes has recently been produced and applied in the clinical management of SNNS. From the viewpoint of surgical methods, modified laparoscopic and endoscopic cooperative surgery with non‐exposed approaches has recently been highlighted as a promising technique to prevent tumor dissemination caused by surgical procedures, and is likely to be clinically applied to SNNS in the future. When carrying out SNNS as a minimally invasive surgery, it is important to consider the balance between post‐surgical quality of life and curability. Future prospective studies on SNNS will greatly contribute to furthering its establishment as a beneficial procedure for patients with early gastric cancer.
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Affiliation(s)
- Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery Field of Oncology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima 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 Field of Oncology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan.,Molecular Frontier Surgery Course of Advanced Therapeutics Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Yoshikazu Uenosono
- Molecular Frontier Surgery Course of Advanced Therapeutics Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Shigehiro Yanagita
- 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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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 2016; 122:386-392. [PMID: 26479552 DOI: 10.1002/cncr.29740] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [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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12
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Morita S, Fukagawa T, Fujiwara H, Katai H. The clinical significance of para-aortic nodal dissection for advanced gastric cancer. Eur J Surg Oncol 2016; 42:1448-54. [PMID: 26876636 DOI: 10.1016/j.ejso.2016.01.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 11/28/2015] [Accepted: 01/06/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Advanced gastric cancer with the risk of extensive nodal involvement has a poor prognosis even after radical surgery. We aimed to comprehensively review the clinical significance of extended radical dissection. METHODS Between 1990 and 1999, 232 patients underwent radical gastrectomy with D2 plus para-aortic lymph node dissection at the National Cancer Center Hospital in Tokyo. We analyzed the short-term surgical and long-term oncological outcomes of these operations. RESULTS Major complications occurred in 34 patients (14.7%). Median operation time was 325 min (range: 182-555) and median blood loss was 715 ml (range: 95-4457). There were 2 (0.9%) hospital deaths. Nodal involvement of the para-aortic area was seen in 33 patients (14.2%). The overall 5- and 10-year survival rates in patients with para-aortic node involvement were 21.2 and 15.2%, respectively. Multivariate analysis of patients with para-aortic node involvement revealed advanced age and metastasis in the interaorticocaval lymph nodes above the left renal vein to be independent risk factors impacting overall survival. CONCLUSIONS PAN dissection has limited applicability and effectiveness to the patients with advanced gastric cancer. Above all, advanced age and metastasis in the interaorticocaval lymph nodes above the left renal vein are significant poor prognostic factor even after radical resection.
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Affiliation(s)
- S Morita
- Surgical Oncology, National Cancer Center, Tokyo, Japan
| | - T Fukagawa
- Surgical Oncology, National Cancer Center, Tokyo, Japan.
| | - H Fujiwara
- Surgical Oncology, National Cancer Center, Tokyo, Japan
| | - H Katai
- Surgical Oncology, National Cancer Center, Tokyo, Japan
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Zhou L, Gong R, Lu X, Zhang Y, Tang J. Development of a Multiplex Real-Time PCR Assay for the Detection of Treponema pallidum, HCV, HIV-1, and HBV. Jpn J Infect Dis 2015; 68:481-7. [PMID: 25866106 DOI: 10.7883/yoken.jjid.2014.416] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Treponema pallidum, hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1, and hepatitis B virus (HBV) are major causes of sexually transmitted diseases passed through blood contact. The development of a sensitive and efficient method for detection is critical for early diagnosis and for large-scale screening of blood specimens in China. This study aims to establish an assay to detect these pathogens in clinical serum specimens. We established a TaqMan-locked nucleic acid (LNA) real-time polymerase chain reaction (PCR) assay for rapid, sensitive, specific, quantitative, and simultaneous detection and identification. The copy numbers of standards of these 4 pathogens were quantified. Standard curves were generated by determining the mean cycle threshold values versus 10-fold serial dilutions of standards over a range of 10(6) to 10(1) copies/μL, with the lowest detection limit of the assay being 10(1) copies/μL. The assay was applied to 328 clinical specimens and compared with enzyme-linked immunosorbent assay (ELISA) and commercial nucleic acid testing (NAT) methods. The assay identified 39 T. pallidum-, 96 HCV-, 13 HIV-1-, 123 HBV-, 5 HBV/HCV-, 1 T. pallidum/HBV-, 1 HIV-1/HCV-, and 1 HIV-1/T. pallidum-positive specimens. The high sensitivity of the assay confers strong potential for its use as a highly reliable, cost-effective, and useful molecular diagnostic tool for large-scale screening of clinical specimens. This assay will assist in the study of the pathogenesis and epidemiology of sexually transmitted blood diseases.
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Affiliation(s)
- Li Zhou
- ABSL-III Laboratory at Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University School of Medicine
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14
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Lee CM, Park SS, Kim JH. Current status and scope of lymph node micrometastasis in gastric cancer. J Gastric Cancer 2015; 15:1-9. [PMID: 25861517 PMCID: PMC4389091 DOI: 10.5230/jgc.2015.15.1.1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2014] [Revised: 01/12/2015] [Accepted: 01/13/2015] [Indexed: 12/14/2022] Open
Abstract
Recently, lymph node micrometastasis has been evaluated for its prognostic value in gastric cancer. Lymph node micrometastasis cannot be detected via a usual pathologic examination, but it can be detected by using some other techniques including immunohistochemistry and reverse transcription-polymerase chain reaction assay. With the development of such diagnostic techniques, the detection rate of lymph node micrometastasis is constantly increasing. Although the prognostic value of lymph node micrometastasis remains debatable, its clinical impact is apparently remarkable in both early and advanced gastric cancer. At present, studies on the prognostic value of lymph node micrometastasis are evolving to overcome its current limitations and extend the scope of its application.
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Affiliation(s)
- Chang Min Lee
- Department of Gastroenterologic Surgery, Korea University Medical Center, Seoul, Korea
| | - Sung-Soo Park
- Department of Gastroenterologic Surgery, Korea University Medical Center, Seoul, Korea. ; Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Jong-Han Kim
- Department of Gastroenterologic Surgery, Korea University Medical Center, Seoul, Korea. ; Department of Surgery, Korea University College of Medicine, Seoul, Korea
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15
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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; 20:3031-3037. [PMID: 23584517 DOI: 10.1245/s10434-013-2973-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [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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Arigami T, Uenosono Y, Yanagita S, Nakajo A, Ishigami S, Okumura H, Kijima Y, Ueno S, Natsugoe S. Clinical significance of lymph node micrometastasis in gastric cancer. Ann Surg Oncol 2013; 20:515-521. [PMID: 22546997 DOI: 10.1245/s10434-012-2355-x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2011] [Indexed: 12/17/2022]
Abstract
Recently, the existence of lymph node micrometastasis (LNM), including isolated tumor cells, has been focused on during the development of molecular diagnostic tools for lymph node metastasis in various malignant neoplasms. In particular, immunohistochemistry and reverse transcription-polymerase chain reaction have been reported to be available for the detection of LNM in gastric cancer. However, at present, the clinical significance of LNM remains unclear in patients with gastric cancer. Therefore, we cannot strategically make light of this issue in clinical management. Currently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery with personalized lymphadenectomy, are widely performed in consideration of postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when selecting surgical treatments for patients with gastric cancer. If minimally invasive surgery based on LNM status was established for patients with early gastric cancer, it could be performed safely. We reviewed the clinical significance of LNM as an important strategic target in patients with gastric cancer.
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Affiliation(s)
- Takaaki Arigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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Wang Z, Dong ZY, Chen JQ, Liu JL. Diagnostic value of sentinel lymph node biopsy in gastric cancer: a meta-analysis. Ann Surg Oncol 2012; 19:1541-1550. [PMID: 22048632 DOI: 10.1245/s10434-011-2124-2] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND The possible application and validity of the sentinel lymph node (SLN) concept in gastric cancer (GC) is still debated. A systematic review to evaluate the diagnostic value of SLN biopsy (SLNB) in GC is urgently needed. METHODS A systematic review of relevant literatures was performed in PubMed, Embase, and The Cochrane Library. A random-effect model was used to pool the data, and subgroup analysis was used to explain the heterogeneities. RESULTS A total of 38 included studies (2,128 patients) were included. The pooled SLN identification rate, sensitivity, negative predictive value, and accuracy were 93.7% (95% confidence interval [95% CI]: 91.1-95.6%), 76.9% (95% CI: 71.6-81.4%), 90.3% (95% CI: 86.9-92.9%), and 92.0% (95% CI: 89.9-93.7%), respectively. Subgroup analysis showed that early T stage, combined tracers, submucosal injection method, conventional open surgery, and usage of immunohistochemistry were associated with higher SLN identification rate and sensitivity. CONCLUSIONS SLNB in GC is technically feasible with an acceptable sensitivity. However, further studies are needed to confirm the best procedure and standard criteria.
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Affiliation(s)
- Zhen Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
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