• Fluorescence
• Gastrectomy
• Indocyanine green
• Near-infrared spcetroscopy
• Stomach neoplasms

• Early gastric cancer
• Frozen section
• Lymph node metastasis
• Sentinel lymph node
• Stomach neoplasm

• Humans
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Male
• Sentinel Lymph Node/pathology
• Sentinel Lymph Node/surgery
• Feasibility Studies
• Female
• Sentinel Lymph Node Biopsy/methods
• Aged
• Middle Aged
• Retrospective Studies
• Lymphatic Metastasis/pathology
• Prospective Studies
• Gastrectomy/methods
• Aged, 80 and over
• Adult
• Frozen Sections/methods
• Lymph Node Excision/methods

• 2311380-2 National Cancer Center of Republic of Korea

• CK19
• OSNA
• meta-analysis
• metastasis
• sentinel lymph nodes

Laparoscopic and endoscopic cooperative surgery is a safe, organ-sparing surgery that achieves full-thickness resection with adequate margins. Recent studies have demonstrated the safety and efficacy of these procedures. However, these techniques are limited by the exposure of the tumor and mucosa to the peritoneal cavity, which could lead to viable cancer cell seeding and the spillage of gastric juice or enteric liquids into the peritoneal cavity. Non-exposed endoscopic wall-inversion surgery (NEWS) is highly accurate in determining the resection margins to prevent intraperitoneal contamination because the tumor is inverted into the visceral lumen instead of the peritoneal cavity. Accurate intraoperative assessment of the nodal status could allow stratification of the extent of resection. One-step nucleic acid amplification (OSNA) can provide a rapid method of evaluating nodal tissue, whilst near-infrared laparoscopy together with indocyanine green can identify relevant nodal tissue intraoperatively.

To determine the safety and feasibility of NEWS in early gastric and colon cancers and of adding rapid intraoperative lymph node (LN) assessment with OSNA.

The patient-based experiential portion of our investigations was conducted at the General and Oncological Surgery Unit of the St. Giuseppe Moscati Hospital (Avellino, Italy). Patients with early-stage gastric or colon cancer (diagnosed via endoscopy, endoscopic ultrasound, and computed tomography) were included. All lesions were treated by NEWS procedure with intraoperative OSNA assay between January 2022 and October 2022. LNs were examined intraoperatively with OSNA and postoperatively with conventional histology. We analyzed patient demographics, lesion features, histopathological diagnoses, R0 resection (negative margins) status, adverse events, and follow-up results. Data were collected prospectively and analyzed retrospectively.

A total of 10 patients (5 males and 5 females) with an average age of 70.4 ± 4.5 years (range: 62-78 years) were enrolled in this study. Five patients were diagnosed with gastric cancer. The remaining 5 patients were diagnosed with early-stage colon cancer. The mean tumor diameter was 23.8 ± 11.6 mm (range: 15-36 mm). The NEWS procedure was successful in all cases. The mean procedure time was 111.5 ± 10.7 min (range: 80-145 min). The OSNA assay revealed no LN metastases in any patients. Histologically complete resection (R0) was achieved in 9 patients (90.0%). There was no recurrence during the follow-up period.

NEWS combined with sentinel LN biopsy and OSNA assay is an effective and safe technique for the removal of selected early gastric and colon cancers in which it is not possible to adopt conventional endoscopic resection techniques. This procedure allows clinicians to acquire additional information on the LN status intraoperatively.

• Laparoscopic and endoscopic cooperative surgery
• Non-exposed endoscopic wall inversion surgery
• Early gastric cancer
• Early colorectal cancer
• Sentinel lymph node
• One-step nucleic acid amplification
• Endoscopic full-thickness resection

• Aged
• Female
• Humans
• Male
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Colonic Neoplasms/surgery
• Laparoscopy/adverse effects
• Laparoscopy/methods
• Lymph Nodes/pathology
• Lymphatic Metastasis/pathology
• Retrospective Studies
• Sentinel Lymph Node Biopsy/methods
• Stomach Neoplasms/genetics
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Organ Sparing Treatments
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/pathology
• Gastrointestinal Neoplasms/surgery
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Nucleic Acid Amplification Techniques

• HIPEC
• PIPAC
• gastric cancer
• hyperthermic intraperitoneal chemotherapy
• peritoneal carcinomatosis
• pressurised intraperitoneal aerosolised chemotherapy
• surgical oncology

• Cervical cancer
• Endometrial cancer
• One-step nucleic acid amplification
• Sentinel lymph node

• Humans
• Female
• Lymphatic Metastasis/pathology
• Prospective Studies
• Nucleic Acid Amplification Techniques/methods
• Endometrial Neoplasms/pathology
• Nucleic Acids
• Lymph Nodes/pathology
• Sentinel Lymph Node Biopsy
• Keratin-19/genetics
• Breast Neoplasms/pathology

• Gastric cancer
• Minimally invasive surgery
• Sentinel lymph node

• OSNA assay
• cytokeratin 19
• lung cancer
• lymph nodes
• metastasis

• Breast cancer
• Breast-conserving surgery
• Incidental irradiation
• Nodal irradiation
• OSNA
• Sentinel lymph node

• Humans
• Female
• Lymphatic Metastasis/pathology
• Neoplasm Recurrence, Local/pathology
• Lymph Nodes/pathology
• Sentinel Lymph Node Biopsy
• Axilla/pathology
• Lymph Node Excision
• Breast Neoplasms/genetics
• Breast Neoplasms/radiotherapy
• Breast Neoplasms/pathology

The endoscopic submucosal dissection (ESD) technique has become the gold standard for submucosal tumors that have negligible risk of lymph node metastasis (LNM), due to its minimal invasiveness and ability to improve quality of life. However, this technique is limited in stage T1 cancers that have a low risk of LNM. Endoscopic full thickness resection can be achieved with laparoscopic endoscopic cooperative surgery (LECS), which combines laparoscopic gastric wall resection and ESD. In LECS, the surgical margins from the tumor are clearly achieved while performing organ-preserving surgery. To overcome the limitation of classical LECS, namely the opening of the gastric wall during the procedure, which increases the risk of peritoneal tumor seeding, non-exposed endoscopic wall-inversion surgery was developed. With this full-thickness resection technique, contact between the intra-abdominal space and the intragastric space was eliminated.

• Endoscopic submucosal dissection
• Laparoscopic endoscopic cooperative surgery
• Non-exposed endoscopic wall-inversion surgery
• Early gastric cancer
• Nodal basin evaluation

Current histopathological staging procedures in colorectal cancer (CRC) depend on midline division of the lymph nodes (LNs) with one section of hematoxylin and eosin staining. Cancer cells outside this transection line may be missed, which could lead to understaging of Union for International Cancer Control Stage II high-risk patients. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid molecular diagnostic tool for LN metastases detection. It is a molecular technique that can analyze the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumor-specific cytokeratin 19 mRNA. Our findings suggest that the OSNA assay has a high diagnostic accuracy in detecting metastatic LNs in CRC and a high negative predictive value. OSNA is a standardized, observer-independent technique, which may lead to more accurate staging. It has been suggested that in stage II CRC, the upstaging can reach 25% and these patients can access postoperative adjuvant chemotherapy. Moreover, intraoperative OSNA sentinel node evaluation may allow early CRC to be treated with organ-preserving surgery, while in more advanced-stage disease, a tailored lymphadenectomy can be performed considering the presence of aberrant lymphatic drainage and skip metastases.

• Colorectal malignancies
• One-step nucleic acid amplification
• Diagnostic accuracy
• Negative predictive value
• Upstaging
• Organ-sparing surgery
• Tailored lymphadenectomy

• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• DNA-Directed RNA Polymerases
• Eosine Yellowish-(YS)
• Hematoxylin
• Humans
• Keratin-19/genetics
• Lymph Nodes/pathology
• Lymphatic Metastasis/pathology
• Neoplasm Staging
• RNA, Messenger/genetics
• Sentinel Lymph Node Biopsy

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.

One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.

Lymph node (LN) status is a key prognostic factor in the decision-making process of different cancer entities, including prostate cancer (PCa). Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies.

To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. With the aim to design and justify future clinical routine use of OSNA in PCa, novel PCa evidence has been included in this review for the first time.

Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques.

OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence might encourage future investigations about its usage in PCa patients to improve LN staging and prognosis.

The prognosis of non-small cell lung cancer greatly depends on the presence of lymph node metastasis, which limits the need for surgery and adjuvant therapy for advanced cancer. One-step nucleic acid amplification of cytokeratin19 (CK19) mRNA was used to detect lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of the new one-step nucleic acid amplification system, which has increased gene amplification efficiency by improving the reagent composition, have shorter preprocessing and measurement times than conventional systems. We aimed to compare the clinical performance of the new system with that of histopathology and the conventional system.

199 lymph nodes from 58 non-small cell lung cancer patients who underwent lymph node dissection were examined intraoperatively using the new system, conventional system, and histopathology.

Lymph node metastasis was diagnosed in 32, 42, and 44 patients using histopathological analysis, the new system, and the conventional system, respectively. Compared with histopathological analysis, the concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value of the new system were 92.0%, 90.6%, 92.2%, 69.0%, and 98.1%, respectively, and compared with the conventional system, the values were 95.0%, 86.4%, 97.4%, 90.5%, and 96.2%, respectively.

The clinical performance of the new one-step nucleic acid amplification system in detecting lymph node metastasis of lung cancer is comparable to that of histopathology and the conventional system; its performance was sufficient for determining the appropriate clinical treatment. The new rapid system can be effectively utilized during lung cancer treatment intraoperatively and postoperatively.

To evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node (LN) metastasis in uterine cancer.

A total of 116 LNs from 30 patients with cervical and endometrial cancer, enrolled in this prospective study, were used. Excised LNs were cut into 4 to 6 blocks at 2 mm intervals, and nonadjacent blocks were alternately subjected to either histological examination or the OSNA assay.

The concordance rate between histological examination and the OSNA assay in cervical cancer and in endometrial cancer was 95.9% and 95.2%, respectively. The sensitivity, specificity, and negative predictive value of the OSNA assay were 80%, 97.7%, and 97.7% in cervical cancer, and 85.7%, 93.3%, and 98.2% in endometrial cancer, respectively. In cervical cancer, discordant results were observed in 2 out of 49 LNs (4.1%); 1 was OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. In endometrial cancer, discordant results were observed in 5 out of 67 LNs (7.5%); 4 were OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive.

The OSNA assay showed high concordance rate with histological examination, sensitivity, and specificity in uterine cancer, suggesting that it could enhance the accuracy of conventional pathological examination for the detection of LN metastasis by reducing false negative rate.

High concordance rate between the one-step nucleic acid amplification (OSNA) assay and histological examination in uterine cancer. OSNA assay demonstrates high sensitivity and specificity for metastatic lymph node detection. Preoperative confirmation of cytokeratin 19 expression in primary tumors may reduce false-negative results.

• Cervical Cancer
• Endometrial Cancer
• One-Step Nucleic Acid Amplification
• Sentinel Lymph Node

• advanced gastric cancer
• one-step nucleic acid amplification
• peritoneal washings

• gastric cancer
• multi-omics analysis
• recurrence risk
• relative expression orderings
• transcriptional signature

In this study, the effectiveness of One-step nucleic acid amplification (OSNA) in combination with ex vivo SLN mapping is compared with conventional histology including immunohistochemistry. OSNA lymph node evaluation has been performed in 41 gastric cancer cases. It showed a high effectiveness with sensitivity, specificity, and accuracy rates of 85.4%, 93.5%, and 92.4%, respectively The LN status could be predicted in 40 cases and led to upstaging in three cases (14%). The OSNA method proved its potential to increase the sensitivity of metastases detection.

Background: In this study, the effectiveness of One-step nucleic acid amplification (OSNA) in combination with ex vivo SLN mapping is compared with conventional histology including immunohistochemistry. Methods: LNs were retrieved from gastrectomy specimens in an unfixed state. After ex vivo SLN mapping using methylene-blue, LNs were sliced to provide samples for histology and OSNA. Results: In total, 334 LNs were retrieved in the fresh state from 41 patients. SLN detection was intended in 40 cases but was successful in only 29, with a correct LN status prediction in 23 cases (79%). Excluding one case out of 41 with a failure likely caused by a processing error, OSNA showed a high effectiveness with sensitivity, specificity, and accuracy rates of 85.4%, 93.5%, and 92.4%, respectively. The LN status could be predicted in all but one case, in which the single positive LN was not eligible for OSNA testing. Moreover, OSNA evaluation led to upstaging from N0 to N+ in three cases (14%). Conclusion: The ex vivo SLN protocol used resulted in a relatively poor detection rate. However, the OSNA method was not hampered by this detection rate and proved its potential to increase the sensitivity of metastases detection.

• OSNA
• gastric cancer
• histology
• lymph node staging
• one-step nucleic acid amplification

• OSNA
• cytokeratin 19
• metastases
• prostate cancer
• sentinel lymph node

• 2016 Research Pool of Carl von Ossietzky University Oldenburg, Oldenburg, Germany

With the increase in the incidence of early gastric cancer (EGC), several endoscopic and laparoscopic approaches, such as endoscopic submucosal dissection and function-preserving gastrectomy, have been accepted as standard treatments. Sentinel node navigation surgery (SNNS) is an ideal surgical option for preservation of most parts of the stomach and consequent maintenance of normal gastric function to improve quality of life in patients with EGC. Although many previous studies and clinical trials have demonstrated the safety and feasibility of the sentinel node concept in gastric cancer, the clinical application of SNNS is debatable. Several issues regarding technical standardization and oncological safety need to be resolved. Recently several studies to resolve these problems are being actively performed, and SNNS might be an important surgical option in the treatment of gastric cancer in the future.

• SENORITA
• Sentinel node navigation surgery
• early gastric cancer
• function-preserving surgery

• Sentinel node
• gastric cancer
• minimally invasive surgery

• Diagnostic accuracy
• Lymph node metastases
• Meta-analysis
• OSNA
• One step nucleic acid amplification

• SLN and lympadenectomy
• cervical cancer
• lymphatic metastasis
• pathology
• uterine cervical neoplasms

Cytokeratin-19 (CK19) has been proven to be commonly expressed by cancer cells in a variety of solid tumors and may serve as a suitable marker of metastases in gastric cancer (GC). Since objective assessment of peritoneal lavage or fluid for free cancer cells (FCC) is essential for clinical decision making in patients with GC, it is important to develop a quantitative and reproducible method for such evaluation. We assessed the possible application of One-Step Nucleic Acid amplification (OSNA) assay as a rapid method for FCC detection in intraoperative peritoneal lavage or fluid of GC patients. Seventy-eight intraoperative peritoneal lavage or fluid samples were eligible for the analysis by conventional cytology and OSNA examination. The concentration of CK19 mRNA in intraoperative peritoneal lavage and fluid was compared with the conventional cytological assessment. CK19 mRNA concentration was detected by OSNA assay. For peritoneal lavage samples, sensitivity and specificity were 83.3% and 87.8%, respectively. In peritoneal fluid, significantly higher CK19 values were observed in patients with serosal infiltration (medians: 100 copies/µL vs. 415.7 copies/µL; p = 0.0335) and lymph node metastases (medians: 2.48 copies/µL vs. 334.8 copies/µL). OSNA assay turns out to be an objective, fast, and reproducible quantitative method of FCC assessment.

• One-Step Nucleic Acid amplification
• free cancer cells
• gastric cancer
• peritoneal fluid
• peritoneal lavage

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/genetics
• Female
• Humans
• Intraoperative Period
• Keratin-19/chemistry
• Keratin-19/genetics
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplastic Cells, Circulating/metabolism
• Nucleic Acid Amplification Techniques/methods
• Peritoneal Lavage
• RNA, Messenger/genetics
• RNA, Messenger/isolation & purification
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology

• Gastrectomy
• Gastric cancer
• Histopathology
• OSNA assay
• Sentinel node mapping

• cervical cancer
• lymphatic metastasis
• neoplasm micrometastasis
• sentinel lymph node
• surgical oncology

• 5-Aminolevulinic acid
• Gastric cancer
• Lymph node metastasis
• Protoporphyrin IX

• Gastric cancer
• Sentinel lymph node

For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients.

We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin–eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed.

Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027).

This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC.

The online version of this article (10.1245/s10434-019-07971-y) contains supplementary material, which is available to authorized users.

• Cervical lymphectomy
• Lymph node metastases
• One-step nucleic acid amplification (OSNA)
• Papillary thyroid carcinoma
• Real-time PCR

• Intraoperative
• Keratin 19
• LN status
• Lung cancer
• Metastasis
• OSNA assay

• Fluorescence imaging
• Gastric cancer
• Indocyanine green
• Sentinel lymph node
• Surgical pathology

Gastric cancer patients represent a rather divergent patient group and in certain carefully selected cases of early forms of gastric cancer the D2 gastrectomy could be considered a more radical procedure than the biological and oncological characteristics of the primary tumor on the gastric wall would require. As any unnecessary dissection increases morbidity without always respective survival benefits, an approach that could accurately predict and actually dictate the exact extent of lymph node dissection would be ideal. It is more than logical the assumption that the standard D2 lymphadenectomy could represent an overtreatment in distinct patients groups such as patients with early gastric cancer with favorable pathological characteristics and clinically negative nodes not suitable for endoscopic treatment because this early stage disease shows limited lymph node metastasis incidence and excellent overall survival. Considering that the D2 gastrectomy has a negative impact on the quality of life of gastric cancer patients due to the post-gastrectomy functional results, a concept of a more targeted lymph node dissection, when appropriate, is certainly appealing. It is yet to be proven whether sentinel lymph node navigation surgery can fulfill such expectations providing the appropriate balance between morbidity and oncological safety in selected gastric cancer patients.

• gastrectomy
• gastric cancer
• laparoscopic assisted gastrectomy
• lymphadenectomy
• sentinel node

Biomarkers are important tools for prompt diagnosis of cancer. This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node (LN) metastasis.

Between 1 December 2014 and 31 December 2015, we prospectively collected samples of gastric-cancer tissues, corresponding matched-pair normal gastric mucosa, and their peri-gastric metastatic and non-metastatic LNs to identify quantitatively reliable genes using quantitative real-time polymerase chain reaction. Relative quantity (RQ) was used to calculate the mRNA expression levels of our target genes. Statistics were calculated using one-way analysis of variance (ANOVA) and Tukey’s multiple comparison test. Analytical graphs were plotted using GraphPad Prism.

Of nine assessed genes, the mRNA levels of inhibin beta A (INHBA) and secreted phosphoprotein 1 (SPP1) were most consistently highly expressed in tumor tissues by 15.4- and 15.6-fold, respectively, as compared with normal tissues (P < 0.001), with 91.3% sensitivity and 95.7% specificity (receiver operating characteristic [ROC] curve area = 0.974) for the former and 82.6% sensitivity and 87.0% specificity (ROC curve area = 0.924) for the latter. Further analysis revealed no differentiating significance of SPP1 mRNA expression between metastatic and non-metastatic LNs (P = 0.470). In contrast, the INHBA mRNA level was up-regulated 4.1-fold in metastatic LNs (P < 0.001), with 80.0% sensitivity and 81.5% specificity (ROC curve area = 0.857), and was also able to successfully differentiate between more severe disease conditions, T3 and T4 (P = 0.003), M0 and M1 (P = 0.043) and different histological variants (intestinal type vs diffuse type, P = 0.019).

Our results showed that INHBA was the most optimally reliable biomarker for diagnosing gastric cancer and LN metastasis.

• Diagnosis
• gastric cancer
• lymph node
• metastasis
• molecular biomarker

• Meta-analysis
• OSNA
• Sensitivity
• Specificity

• cea
• gastric cancer
• network meta-analysis
• sensitivity and specificity
• tumor biomarkers

• Biomarkers, Tumor/blood
• Early Detection of Cancer/methods
• Humans
• Neoplasm Staging
• Network Meta-Analysis
• Research Design
• Stomach Neoplasms/blood
• Stomach Neoplasms/pathology

• X breakpoint
• echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase; synaptotagmin and synovial sarcoma
• gene translocation
• immunoglobulin heavy chain gene and B cell leukemia/lymphoma 2
• loop-mediated isothermal amplification

• lymph nodes
• one-step nucleic acid amplification
• papillary thyroid cancer

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.

• fluorescence imaging
• gastric cancer
• laparoscopic and endoscopic cooperative surgery
• lymph node metastasis
• sentinel node navigation surgery

• Gastric cancer
• early gastric cancer (EGC)
• guidelines
• lymph node navigation (LN navigation)
• minimally invasive surgery
• surgical oncology