{"paper_id":"a8bccf63-ac49-4225-bc93-d75a43409d52","body_text":"Narrow-band imaging (NBI), an on-demand, real-time, endoscopic imaging technique, was developed to enhance the visualization of the mucosal vascular network and surface texture for the purpose of improving tissue differentiation, characterization and diagnosis ( 1 ).\nThe interaction of particular tissue structures with light is wavelength-dependent and augmentation of particular mucosal features via NBI is achieved through observation of light transmission at selected wavelengths (or colors) ( 2 ).\nIn the NBI system, selective light transmittance is conducted via optical filtering of white light (WL). Specifically, NBI uses two discrete bands of light, a blue band at 415 nm and a green band at 540 mm, to create a high-contrast image of the tissue surface, which allows enhanced visualization of blood vessels ( 3 ). The two bands correspond to the peak light absorption of hemoglobin, thus permitting NBI to visualize the blood vessels with greater clarity and accuracy on the surface of the analyzed tissues than observation with WL ( 3 ).\nIn clinical practice, there is currently widespread use of NBI to provide an improved examination of the gastrointestinal system, including the stomach and large intestine, esophagus and pharynx, as well as of the lungs, urinary tract and oropharynx. This technique, which has been termed ‘optical biopsy’, has brought achievements of earlier diagnosis by substantially improving the qualitative diagnosis of the depth and grade of invasion of atypical lesions ( 4 ).\nThe aim of the present study was to perform a systematic review of all available studies evaluating the use of NBI in gynecology clinical practice for the detection of benign and malignant lesions.\n\nThe following electronic databases were searched: PubMed (1950-2021), Google Scholar (2004-2021) and Cochrane Library (2010-2021). The electronic literature search was mostly performed between January 2020 to February 2021. The search included the following medical subject headings or keywords: ‘Narrow-band imaging’ and ‘gynecology’. The last search was performed on 08/02/2021.\nThe systematic review was performed and the flowchart diagram was drawn according to the Preferred Reporting Items for Systematic Reviews and Metanalyses statement ( 5 ).\nFull-text articles published in peer-reviewed journals and written in the English language were deemed eligible to be included in the review. Studies that did not fulfill the following criteria were excluded from the review: i) Conference abstracts and studies not providing sufficient clinical data; and ii) studies reporting narrow-band imaging utilization in animals, in surgical specimens or in an  in vitro  environment.\nAll types of studies were included, namely randomized controlled or observational studies, case series and case reports. The selected eligible articles were compared and discrepancies were resolved by discussion. The final decision on eligibility was made by the senior investigator (PP) whenever discrepancies had not been resolved through discussion.\nTwo authors (PP and KK) independently extracted information, while SS, CK, VA, PT and NA checked the extracted information and tabulated the data. NV checked the results and approved the study.\nFrom the eligible studies, the following clinical data were obtained: Author and year of publication; the time period of enrolment of the study population; the country and city in which the study was performed; the type of study; the setting of the hospital (single- or multi-university study); the number of patients; the age of the patients; the inclusion criteria for surgery; the interventions performed; the endoscopic system used in each study; the outcome of the studies; and comments on different studies. The references of the selected studies were scrutinized for additional information not obtained by the initial search.\nThe Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the quality of the primary diagnostic accuracy studies. Via this tool, risks for bias may be evaluated in the following four key domains: i) Selection of participants; ii) index (diagnostic) test; iii) reference standard; and iv) flow and timing of the study ( 6 ).\nThrough the use of the Case Report (CARE) guidelines checklist, the information quality of case reports was evaluated, specifically assessing the following items: Patient information, the presence of timeline information, diagnostic assessment, clinical findings, therapeutic intervention and outcomes ( 7 , 8 ).\nData obtained from the selected studies were entered into an Excel v160 spreadsheet (Microsoft Corporation 2018). Descriptive statistical analyses was performed using SPSS version 23 (IBM Corporation) and Excel version 16.0 (Microsoft Corporation, 2018). The number of publications were calculated per year and per country, and the median age of participants in the selected studies was also calculated.\n\nThe literature search identified a total of 3,836 studies, i.e., 3,800 articles through Google Scholar, 32 articles through the PubMed database and four through the Cochrane Library database. The flowchart of the study selection process is displayed in  Fig. 1 . After removing duplicates and irrelevant articles, 256 articles were considered for further evaluation. Further assessment excluded 215 articles for various reasons (non-eligible, non-English literature, animal studies and articles providing insufficient information). Finally, 31 studies reporting on a total of 3,128 female patients were included in the review.\nOf the selected studies, 10 (32%) were case reports ( 9-18 ), 19 (61.2%) were prospective studies ( 11 , 12 , 18-32 ) and two studies (6.4%) were randomized controlled trials ( 33 , 34 ). The selected studies had publication dates ranging from 2007 to 2020.\nThe frequency of publications per year and the percentage of publications by country are presented in  Fig. 2 . The years with the highest frequency of publications were 2010 and 2011 with 5 studies produced each year and the country which produced the highest number of studies was Japan with 11 studies ( 13 , 18 , 21 , 22 , 28 , 31-33 , 35 ), followed by Italy with 8 studies ( 9 , 10 , 15-17 , 19 , 20 , 36 ).\nA total of 11 studies described the use of NBI in hysteroscopy for the detection of endometrial pathologies ( 9 , 10 , 19-25 , 36 , 37 ) and another 11 studies reported the use of NBI in laparoscopy for the detection of peritoneal endometriosis ( 11-13 , 26-30 , 33 , 34 , 37 , 38 ). Furthermore, three articles dealt with the use of NBI in digital colposcopy for the detection of lower genital tract pathologies ( 14 , 31 , 32 ) and three articles reported on the use of NBI in laparoscopy for the detection of peritoneal metastases associated with ovarian cancer and other gynecological malignancies ( 15-17 ).\nDetails on the selected studies reporting the use of NBI in hysteroscopy are presented in  Table I . A total of 11 studies were included in the review, dating from 2009-2020 with a combined cohort of 2,424 female patients ( 9 , 10 , 19-25 , 36 , 37 ). Of these, eight studies were prospective studies (Canadian Task Force classification, II-2) ( 19 , 23 , 36 ) and two studies were case reports ( 9 , 10 ). All studies were designed in university settings, two studies were performed in multicentric university settings ( 20 , 36 ) and two studies were reported at international congresses as conference reports ( 10 , 24 ). All of the patients presented with abnormal uterine bleeding (AUB). The median age of the patients was 45.5±10.5 years. A total of four studies were performed in outpatient office settings using a vaginoscopic approach without any general anesthesia ( 19 , 21 , 23 , 36 ). Conventional hysteroscopy under general anesthesia was performed in seven studies ( 10 , 24 , 25 ). Operative hysteroscopy was performed in all cases and histology specimens were obtained in each case. Olympus Exera II (Olympus Corporation) was the main video system used in the majority of studies.\nNBI hysteroscopy demonstrated increased sensitivity compared with WL imaging hysteroscopy for the detection of endometrial cancer in four studies ( 20 , 23 , 24 ).\nThe sensitivity of NBI and WL hysteroscopy for endometrial cancer reported by individual studies was 78.6 vs. 63.7%, P<0.001( 23 ), 93 vs. 81%, P<0.05( 36 ), 94.7 vs. 84.4%, P<0.05( 20 ) and 98.1 vs. 73.6% P<0.001( 24 ). Increased sensitivity of NBI vs. WL for the detection of atypical endometrial hyperplasia - high-risk hyperplasia (HRH) was reported in five studies ( 10 , 20-23 ). The reported sensitivity of NBI vs. WL for HRH was 60 vs. 20%, P<0.005( 36 ), 78.38 vs. 64.86%, P<0.005( 20 ), 78.6 vs. 63.7%, P<0.001( 23 ), 93.5 vs. 82.6%, P=0.006( 24 ) and 97.2 vs. 82.6%, P<0.005( 21 ).\nNone of the 11 studies reported any adverse effects or complications related to the surgical techniques in all instances.\nDetails on the selected studies reporting on the use of NBI in laparoscopy for the detection of peritoneal endometriosis are provided in  Table II . A total of 11 studies were included in the present review, dating from 2007 to 2019 with a population of 626 female patients in total ( 11-13 , 26-30 , 33 , 34 , 38 ). The mean age was 35.5±3.6 years. A total of three studies were case reports ( 11 , 12 , 29 ), three were studies with a randomized design ( 13 , 34 , 38 ) and five were had a prospective design lacking randomization ( 26-29 , 33 ). In all studies, laparoscopy with a 0-degree 10-mm scope was performed, except for two studies where intestinal endoscopy was utilized ( 13 ), while one study reported on the use of a 0-degree 12-mm scope ( 30 ). NBI improved the detection rate by 53% for smaller endometriotic lesions previously not detected on WL imaging laparoscopy ( 26 ). Another study reported that 82.7% of endometriotic lesions were detected using NBI compared with 55.9% of lesions detected by WL imaging ( 27 ). The detection rate of endometriotic lesions with NBI was 100% in a randomized controlled trial with 167 female patients ( 34 ). Another randomized controlled trial assessed quality of life in two study groups: One group underwent laparoscopy with WL and the other with NBI. No difference in pain and quality of life was observed between the two study groups ( 34 ). When combined with WL, NBI was reported to provide an additional predictive value of 86% for the detection of endometriotic lesions, if a positive diagnosis was made under WL imaging alone ( 29 ). NBI and WL combined with 3D imaging was able to increase the sensitivity rate up to 91% ( 13 ).\nOlympus Exetera (Olympus Corporation) was the system used for NBI in all of the studies. None of the 11 studies reported any adverse effects or complications related to the surgical techniques.\nDetails on the selected studies reporting on the use of NBI in laparoscopy for the detection of cervical lesions and gynecological malignancies are listed in  Table III . A total of 9 studies were included in the review, dating from 2010 to 2020. Of these, four studies were prospective studies ( 31 , 32 , 35 , 39 ) and five studies were case reports ( 14-18 ). The total number of patients was 156 and the mean age was 43.3±17.25 years. Uterine cervical pathology was investigated with NBI in five studies ( 14 , 18 , 31 , 32 , 35 ) and peritoneal implants were investigated with NBI in four studies ( 15-17 , 39 ).\nThe vascular pattern of lesions was examined in 21 patients with early and  in situ  cervical adenocarcinoma using NBI ( 13 ). The authors classified the colposcopic lesions according to the pattern described by Wright ( 40 ). The vascular pattern was visualized in 18 patients (86%); the authors concluded that NBI colposcopy depicts the vascular pattern on the cervix in early glandular disease better than conventional colposcopy. Nishiyama  et al  ( 32 ) proposed a novel microvascular classification. They used flexible magnifying endoscopy with NBI in 10 patients with cervical lesions; the detection rate was 90% (9/10) ( 32 ). NBI assisted in the detection of a rare melanoma of the cervix in a case report ( 14 ). Furthermore, NBI was utilized in laparoscopy for the detection of peritoneal metastasis in a series of 95 female patients undergoing surgery for various gynecological malignancies, as reported by Aloisi  et al  ( 39 ). They determined that NBI increased the number of the detected peritoneal abnormalities; however, no statistically significant differences were observed in the identification of histologically confirmed metastatic disease (P=0.18) ( 39 ).\nA significantly greater number of peritoneal abnormalities were identified with NBI than with standard WL imaging. However, no statistically significant differences were observed in the identification of histologically confirmed metastatic disease ( 39 ). In addition, NBI proved to be useful in the laparoscopic detection of early peritoneal implants in three case reports ( 15-17 ). Kobara  et al  ( 18 ) indicated that NBI increased the sensitivity, specificity, accuracy and positive predictive value for the detection of cervical intraepithelial lesions-3 (CIN-3) in comparison with conventional colposcopy. NBI with a gastroscope assisted the detection of high-grade cervical intraepithelial lesions in two patients, while these lesions were not identified by conventional colposcopy ( 18 , 35 ). None of the nine studies reported any adverse effects or complications related to the surgical techniques.\nThe CARE guidelines were followed to perform the quality assessment of the case reports ( 7 ). A total of 10 case reports were assessed for their quality ( 9-18 ). The results are presented in  Fig. 3 . Approximately 30% of the case reports had a low quality in terms of presentation of demographic information. In total, 55% of the case reports included had low quality regarding the presentation of the patients' history with timeline information. Furthermore, 45% of the case reports were of poor quality in terms of information about differential diagnosis.\nThe QUADAS-2 tool was used to assess the risk of bias in four domains. The results are presented in  Fig. 4 . In total, 19 studies were assessed. Of these, 17 had a prospective design lacking randomization and two were randomized controlled trials with control groups. A total of 9 studies were indicated to have a high risk of bias ( 24 , 25 , 27 , 29 , 30-32 , 34 , 36 ) and 10 studies were determined to have a low risk of bias ( 19-21 , 23 , 28 , 30 , 32 , 37-39 ).\nThe outbreak of the COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has produced a public health emergency of international concern, with all of the data demonstrating that the spread of the virus mainly occurs via respiratory droplets during close contact ( 41 , 42 ). During this ongoing pandemic, recommendations regarding laparoscopy and endoscopy with NBI should follow the general international recommendations for laparoscopy.\nHowever, the potential risk of infection through endoscopically generated bioaerosols may possibly be increased as a result of three important factors pertaining to laparoscopy. These are the following: i) Use of gas insufflation during entry and intra-operatively; ii) generation of bioaerosols via electrosurgery, which is a cornerstone of endoscopy; and iii) the potential for gas leaks in the operation room, which may lead to elevated viral loads in the air ( 41 , 42 ). Precautions should be taken during gynecological endoscopy with NBI, adhering to the international recommendations concerning SARS-CoV-2 ( 41-43 ).\nRegarding elective surgery, it is recommended that universal testing for SARS-CoV-2 infection is conducted whenever possible within 40 h preceding surgery. Should a case of SARS-CoV-2 be positively confirmed, it is advisable to delay surgery, although exceptions may be made for urgent cases, e.g. malignancies.\nIt has been reported that laparoscopies have a larger potential for aerosol spread than hysteroscopies ( 41-43 ), while laparotomies have a lower risk of aerosol spread in comparison to laparoscopies ( 41-43 ). However, endoscopy is generally preferred due to the one-day stay and the smaller exposure to a hospital environment.\nStrict safety measures regarding the pressure of the gas and pressure of the fluid should be applied to minimize the possibility of spread. In cases where local anesthesia may be used, it is expected to be beneficial for the patient, minimizing the risk of infection, which may occur after the intubation and the extubation procedure.\nFurther guidelines issued by the different medical associations such as International Society for Gynecologic Endoscopy (ISGE;  www.isge.org ) and American Society of Gynecologic Laparoscopists (AAGL;  https://www.aagl.org/ ) ( 42 , 43 ) will provide additional pertinent and vital data during the current fight against the pandemic.\nNBI, which is now regularly used in gynecology, is a relatively new optical technology and the present systematic review is, to the best of our knowledge, the most updated and extensive of its kind that has been provided on this method to date. Due to the relatively small number of randomized controlled trials, observational studies were included in spite of providing a lower level of evidence. While precise and clear inclusion criteria were employed for the preparation of the present review, the small sample size of the trials included and the overall absence of definitions of primary outcomes inevitably reduced the quality of the present review. Furthermore, risk of bias in the flow and timing domains was frequently present. Therefore, it was not possible to perform a pooled data-analysis or meta-analysis. While case reports were included, the majority of these studies were well-designed and mostly provided their evidence clearly and accurately, according to the quality assessment using the CARE (Case report) guidelines.\n\nThe NBI system for image-enhanced endoscopy was first conceived and developed in May 1999 and the product was launched by Olympus Corporation in May 2006( 21 ).\nThe major advantages of the NBI system are the enhancement of endoscopic visualization of superficial neoplastic lesions and their microvascular architecture. Conventional endoscopic diagnosis using WL, by contrast, is based on subtle morphological changes, e.g., superficially elevated, flat or depressed lesions, and on minimal changes in color such as reddish discoloration ( 19 ).\nThe present systematic review demonstrated that the application of NBI in gynecological endoscopy has the potential to improve the diagnosis of endometriosis. It may also have the potential to enhance the diagnosis of premalignant and malignant lesions in the fields of hysteroscopy, laparoscopy and colposcopy.\nWhile Kisu  et al  ( 44 ) performed a review in 2012, the present systematic review is substantially updated and includes quality assessment of the studies according to the QUADAS-2 and the CARE guidelines ( 6 , 7 ).\nNBI has proven to be an efficacious approach for the diagnosis of endometrial cancer and hyperplasia, while thorough training improves the trainee's diagnostic skills to an extent depending on their previous hysteroscopic experience ( 37 ). However, it must be stressed that NBI laparoscopy was not superior in the detection of peritoneal metastases in comparison with standard WL laparoscopy alone, which was reported by Aloisi  et al  ( 39 ) and Schnelldorfer  et al  ( 45 ).\nA significantly greater number of peritoneal abnormalities were identified with NBI than with standard WL. However, no statistically significant differences were observed in the identification of histologically confirmed metastatic disease. In fact, of the eight additional suspicious-appearing nodules visualized with NBI, only three were confirmed as malignant on final pathology, and none of the patients had surface malignancies identified with NBI that were not also seen with WL, even if in a different area ( 39 ). Aloisi  et al  ( 39 ) pointed out that further exploration of the use of NBI/3D WL imaging is required; this will now be further evaluated in a large randomized clinical trial with clinically relevant endpoints, with adequate power, quality control and measures ( 44 ). This will be according to the Idea, Development, Exploration, Assessment and Long-term Study (IDEAL) framework, describing 5 stages of evolution for new surgical therapeutic interventions. IDEAL is an important driver for future incremental and evidence-based modifications ( 46 ).\nFurthermore, another limitation is the extension of the surgical time, particularly in laparoscopic procedures with the use of NBI. Lier  et al  ( 30 ) reported a median extension of surgical time of 30 min with NBI due to thorough inspection of the peritoneum and histological sampling. The clinical question is whether an improved detection of endometriosis with NBI/3D imaging also affects the long-term clinical outcomes after surgery, such as reintervention rates, pain-free interval and quality of life ( 30 ).\nA shortcoming, particularly with the methodology reported by Barrueto  et al  ( 34 ), is the low specificity. This may result in unnecessary resection of healthy tissue, producing postoperative neuropathic pain and adhesion formation.\nIn the study by Surico  et al  ( 20 ), only a small number of patients were recruited, while the study was performed at a single academic institution. Furthermore, the accuracy of NBI hysteroscopy in the prediction of histological findings via analysis of interobserver variability was not assessed ( 20 ).\nWang  et al  ( 37 ) reported that the physician who performs hysteroscopy must be familiar with endometrial lesions, which are influenced by estrogen and progesterone secretion. Endometrial necrosis may not only be observed in malignant lesions, but also frequently appears in benign hyperplastic lesions associated with abnormal uterine bleeding. These factors increase the difficulty of hysteroscopic diagnosis; therefore, the learning curve for the diagnosis of endometrial neoplasms is relatively long. The authors report that >200 hysteroscopic cases are required to be performed by physicians until proficiency is reached ( 37 ).\nThe drawback of NBI colposcopy is that the system is expensive; thus, widespread use of it is limited and is particularly unsuitable for application in developing countries. It may be appropriate to use for educational purposes in cancer center hospitals or university hospitals ( 31 ).\nIn conclusion, conventional WL imaging in gynecological endoscopy is now well-established as a highly sensitive and specific technique for the diagnosis of intrauterine diseases and the present study clearly indicated that the NBI system, when applied by an expert and experienced surgeon, is capable of enhancing diagnostic accuracy. Furthermore, NBI may increase the diagnostic skills of trainees. Future directions of research should take into consideration the reoperation rates, recurrence and overall cost. Evidence-based frameworks such as IDEAL should be implemented in order to improve clinical practice. Certainly, there is a requirement for large-scale, multicenter, randomized trials to substantiate the present results as to the potential for use of NBI in gynecology, the application of which may improve patients' oncological outcomes and thus their quality of life.","source_license":"CC0","license_restricted":false}