Clinicopathological features of narrow‐band imaging endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms

To reveal clinicopathological features of narrow‐band imaging (NBI) endoscopy and immunohistochemistry in ultraminute esophageal squamous neoplasms. If a lesion diameter was smaller or same compared with a width of closed biopsy forceps, a lesion was defined to be an ultraminute lesion. Twenty‐five consecutive patients with 33 ultraminute esophageal lesions that were removed by endoscopic mucosal resection were included in the present study. We conducted two questionnaire surveys of six endoscopists by their retrospective review of endoscopic still images. The six endoscopists evaluated the endoscopic findings of the ultraminute lesions on still images taken by conventional white‐light imaging endoscopy and non‐magnified NBI endoscopy in the first questionnaire, and taken by magnified NBI endoscopy in the second questionnaire. An experienced pathologist who was unaware of any endoscopic findings made histological diagnosis and evaluated immunoexpression of p53 and Ki67. The 33 ultraminute lesions were all determined to be either 11 high‐grade intraepithelial neoplasias (HGIENs) or 22 low‐grade intraepithelial neoplasias (LGIENs). The tumor diameters were histologically confirmed to be <3 mm. All of the ultraminute tumors were visualized as unstained areas and brownish areas by real‐time endoscopy with Lugol dye staining and non‐magnified NBI endoscopy, respectively. All of the ultraminute IENs were visualized as brownish areas by real‐time non‐magnified NBI endoscopy. Three of the 25 patients with the ultraminute IENs (12%) had multiple brownish areas (more than several areas) in the esophagus on real‐time non‐magnified NBI endoscopy. All of the ultraminute IENs were visualized as unstained areas by real‐time Lugol chromoendoscopy. Twenty of the 25 patients (80%) had multiple unstained areas (more than several areas) in the esophagus on real‐time Lugol chromoendoscopy. The first questionnaire survey revealed that a significantly higher detection rate of the ultraminute IENs on non‐magnified NBI endoscopy images compared with conventional white‐light imaging endoscopy ones (100% vs. 72%, respectively: P < 0.0001). The second questionnaire survey revealed that presence rates of any magnified NBI endoscopy findings were not significantly different between HGIENs and LGIENs. Proliferation, dilation, and various shapes of intrapapillary capillary loops indicated remarkably high presence rates of more than 90% in both HGIENs and LGIENs. Six of 22 LGIENs (27%) and 3 of 11 HGIENs (27%) show a positive expression for p53. None of peri‐IEN epithelia was positive for p53. A mean of Ki67 labeling index of LGIENs was 33% and that of HGIENs 36%. Ki67 labeling index was significantly greater in the LGIENs and HGIENs compared with that in the peri‐IEN epithelia. There were no significant differences in p53 expression and Ki67 labeling index between the HGIENs and LGIENs. Non‐magnified/magnified NBI endoscopy could facilitate visualization and characterization of ultraminute esophageal squamous IENs. The ultraminute HGIENs and LGIENs might have comparable features of magnified NBI endoscopy and immunohistochemistry.     

Lugol chromoendoscopy as a diagnostic tool in so-called endoscopy-negative GERD

BACKGROUND: Esophageal mucosal breaks are found in less than half of patients with typical reflux symptom. Thus, endoscopy appears to be an insensitive test for GERD. Lugol chromoendoscopy has been used to detect early esophageal cancer, which is difficult to recognize by routine observation without dye staining. The aim of this study was to determine the efficacy of Lugol chromoendoscopy in the diagnosis of so-called endoscopy-negative GERD (ENRD). METHODS: The study was conducted with 61 patients (21 women; mean age of 59.8 years) with reflux symptoms and 42 controls (15 women; mean age, 65.0 years). In the absence of any esophageal mucosal abnormalities at conventional endoscopy, Lugol's iodine solution was sprayed onto the esophageal surface, followed by evaluation of the staining pattern. When Lugol-unstained streaks were observed at chromoendoscopy, biopsy specimens were obtained from unstained streaks and from adjacent stained mucosa. Histologic evaluation included basal cell hyperplasia, papillary length, and cellular infiltration. RESULTS: Twenty-two (36%) of 61 patients with reflux, and 4 (10%) of 42 controls had visible esophagitis by conventional endoscopy. Lugol chromoendoscopy was performed in the remaining 39 patients and 38 controls. The entire esophageal mucosa was uniformly stained dark brown in 20 patients with reflux and 37 controls. In the remaining 19 patients with reflux and in one control, several unstained streaks were observed in the distal esophagus (p < 0.0001). Histologically, Lugol-unstained mucosa showed a significantly thicker basal cell layer (30.9% +/- 7.6% vs. 12.3% +/- 4.5% of total epithelial thickness, mean +/- standard deviation [SD], p < 0.01) and longer papillae (57.9% +/- 12.6% vs. 38.1% +/- 12.6% of total epithelial thickness, mean [SD], p < 0.01) compared with stained mucosa. In addition, infiltration of lymphocytes in the epithelium was significantly increased in unstained mucosa than in stained mucosa (p < 0.01). CONCLUSIONS: Visible unstained streaks by Lugol chromoendoscopy seem to be indicative of mucosal injury, which was not detectable by conventional endoscopy. Lugol chromoendoscopy is simple and could be useful for the diagnosis of ENRD. This method could be appealing for the endoscopist as it is easy, safe, and can be performed at the same endoscopic session.     

Esophageal squamous cell carcinoma - precursor lesions and early diagnosis

Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis.Early detection is highly desirable,since surgical and endoscopic resection offers the only possible cure for esophageal cancer.Population screening should be undertaken in high risk areas,and in low or moderate risk areas for people with risk factors (alcoholics,smokers,mate drinkers,history of head and neck cancer,achalasia and lye stricture of the esophagus).Esophageal balloon cytology is an easy and inexpensive sampling technique,but the current methods are insufficient for primary screening due to sampling errors.Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection.It may be enhanced by several techniques such as dye and optic chromoendoscopy,magnifying endoscopy,and optical-based spectroscopic and imaging modalities.Since more than 80% of SCCE deaths occur in developing countries,where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable,the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy,since it is easy,accurate,inexpensive and available worldwide.In ideal conditions,or in developed countries,is it reasonable to think that optimal detection will require a combination of techniques,such as the combination of Lugol’s chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique.The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.     

Mucosal cancer of the esophagus that presented significant changes of endoscopic findings in repeated observations

We report our experience of a very unique case with superficial esophageal cancer presenting significant changes of endoscopic findings within 2 months. A 60‐year‐old man was referred to our hospital because of abrupt and severe chest pain. Upper gastrointestinal endoscopy demonstrated a shallow depressed lesion covered with whitish slough at the middle thoracic esophagus, which was identified as an unstained area by iodine dye spray. In the lower thoracic esophagus, we did not detect any abnormality during initial endoscopy. Although we diagnosed this lesion as atypical esophagitis, histological examination of the biopsy specimen confirmed squamous cell carcinoma. Furthermore, the endoscopic appearance showed dramatic changes over 2 months. The initial lesion at the middle thoracic esophagus gradually diminished, while the mucosa became slightly clouded in the lower thoracic esophagus. This cloudy area became unstained after iodine dye spray. The unstained area of the lower thoracic esophagus gradually spread. We performed four endoscopic mucosal resections separately in 4 days over a period of 5 months. All of the specimens were shown to be squamous cell carcinoma on histological examination. The patient is on endoscopic surveillance and over a period of 1 year, there has been no recurrence.     

Diagnostic ability of blue laser imaging combined with magnifying endoscopy for early esophageal cancer

BackgroundBlue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light source developed for narrow-band light observation.AimsTo evaluate the value of BLI combined with magnifying endoscopy (M-BLI) for the diagnosis of early esophageal cancers (EECs).MethodsThis single-center prospective study analyzed 149 patients with focal esophageal lesions detected with white light endoscopy (WLE) at Renmin Hospital of Wuhan University between April 2015 and June 2017. In this study, patients were examined sequentially with narrow-band imaging combined with magnifying endoscopy (M-NBI), M-BLI and 1.25% Lugol’s iodine chromoendoscopy. The concordance between endoscopic diagnosis and pathological diagnosis was evaluated using the agreement (kappa) test. The paired chi-square test was used to compare the concordance of M-NBI, M-BLI and Lugol’s iodine chromoendoscopy.ResultsThis study analyzed 153 lesions (four patients had two lesions each). The sensitivity, specificity, accuracy, concordance rates and kappa value of M-BLI were 95.2%, 91.9%, 85.7%, 92.8% and 0.891, respectively; those of M-NBI were 95.2%, 92.8%, 87.5%, 93.5% and 0.906; and those of Lugol’s iodine chromoendoscopy were 95.2%, 94.6%, 91.3%, 94.8% and 0.936.ConclusionM-BLI has a diagnostic profile similar to that of M-NBI and could improve the accuracy of EEC diagnosis.     

Manejo del carcinoma de células escamosas de esófago precoces a través de la disección endoscópica submucosa

The incidence of esophageal cancer is steadily increasing worldwide. Outcome is poor, given that the majority of cases are diagnosed at advanced disease stages. However, when detected at early stages, esophageal tumors can be curatively treated through less invasive methods, resulting in a 5-year survival rate above 90%. Therefore, it is essential to identify the high-risk population and recommend those patients undergo screening using high-resolution endoscopy, adding the resources of chromoendoscopy with Lugol’s solution (or digital chromoendoscopy) and magnification. Such systematized examination makes it possible to recognize early-stage esophageal neoplasia and propose endoscopic submucosal dissection as treatment. In that procedure, the tumor is resected en bloc, resulting in lower morbidity and mortality, compared with previous standard treatment, including early-stage esophagectomy. The present article is a review of the latest advances in the management of superficial esophageal tumors through endoscopic submucosal dissection.     

Präkanzerosen im Ösophagus

Modern high-resolution video endoscopes allow detailed examination of the esophageal mucosa and diagnosis of early neoplastic changes in the gastrointestinal tract. Whereas Barrett’s esophagus is a precancerous condition that can develop into adenocarcinoma, there is no defined precancerous lesion for squamous cell carcinoma. Various diseases are associated with the development of esophageal squamous cell carcinoma. Chromoendoscopy has become an established method in the diagnostic work-up for better visualization of early neoplasia. If Barrett’s esophagus is present, acetic acid spraying or virtual chromoendoscopy can be used to accentuate the display of superficial gyriform structures in the mucosa. The gold standard for detecting squamous cell carcinoma is still the use of Lugol solution. When early neoplasia is suspected, diagnostic endoscopic resection should be performed. This allows precise histological assessment of the tumor. Early diagnosis of neoplastic changes in the esophagus provides patients not only with the option of curative therapy but also with a good quality of life through preservation of the esophagus.     

Lugol Staining Pattern and Histology of Esophageal Lesions

To analyze the relationship between Lugol unstained areas and their histologic features, we applied the Lugol test to 24 specimens of resected esophagus. The staining patterns were graded into four types: grade I, hyperstaining; grade II, normal greenish brown staining; grade III, less intense staining; and grade IV, unstained. Most of the grade IV lesions were invasive carcinomas, carcinomas in situ , or severe dysplasia. The carcinomas in situ and the intraepithelial extension of the carcinomas, which were difficult to detect, were clearly shown as grade IV. On the other hand, moderate to mild dysplasia or atrophy showed grade III staining. Grade IV lesions showed well-demarcated sharp margins, whereas grade III lesions showed ill-demarcated dull margins. The grade III carcinomas, however, by the Lugol test, showed well-demarcated margins. Histologic evaluation disclosed that the staining intensity reflected well the thickness of the glycogen-containing cell layer in the lesion. The sharpness of the margin reflected the abrupt or gradual change from the glycogen-containing to non-containing cell layers. These findings suggest 1) the usefulness of the staining pattern of the Lugol test for the diagnosis of esophageal lesions such as squamous cell carcinoma and severe dysplasia, and 2) the usefulness of the Lugol test for precise delineation of the proximal resection line during surgery of esophageal carcinomas with unexpected wide extension.     

A tiny esophageal cancer diagnosed accurately by magnifying endoscopy and endocytoscopy: report of a case

An 82-year-old woman presented for a periodic endoscopic examination after radiotherapy and endoscopic mucosal resection (EMR) of a cancer in the esophagus. Conventional endoscopy demonstrated a tiny, flat, reddish lesion about 1 mm in diameter proximal to the scar of the previous esophageal EMR. Observation after iodine staining showed an apparent unstained area in the lesion. Magnifying observation using a Q240Z (Olympus, Tokyo, Japan) revealed a clearly demarcated aggregation of dilated intrapapillary capillary loops in this part of the lesion. Endocytoscopic observation (XEC120U prototype; Olympus) showed increased cellular density and irregularity of the epithelial nuclei. Endoscopic mucosal resection of the lesion was performed. Pathological studies of the resected specimen revealed a squamous cell carcinoma, maximal diameter 920 μm, confined to the epithelium. We believe that the Endocytoscope has the potential to reduce biopsy histology in cases of esophageal squamous cell carcinoma.     

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow‐up period (median, 24 months), the 3‐year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.     

Endoscopic diagnosis and treatment of early esophageal squamous neoplasia

Esophageal cancer is one of the leading causes of cancer-related death and is associated with high morbidity and mortality.It carries a poor prognosis as more than half of patients present with advanced and unresectable disease.One contributing factor is the increased risk of lymph node metastases at early stages of disease.As such,it is essential to detect squamous cell neoplasia (SCN) at an early stage.In order to risk stratify lesions,endoscopists must be able to perform image enhanced endoscopy including magnification and Lugol's chromoendoscopy.The assessment of both the horizontal extent and depth of any lesion is also of utmost importance prior to treatment.Endoscopic mucosal resection and submucosal dissection remain the standard of care with literature supportive their respective use.Radiofrequency ablation and other endoscopic treatments are currently available although should not be considered first line at this time.Our objective is to review the current options for the endoscopic diagnosis and treatment of esophageal SCN.     

Assessment of novel endoscopic techniques for visualizing superficial esophageal squamous cell carcinoma: autofluorescence and narrow-band imaging

Lugol chromoendoscopy (LCE) is a useful technique for visualizing superficial esophageal squamous cell carcinoma (SESCC), but the stimulating effect of the Lugol solution can sometimes cause clinical problems. Newly developed techniques such as narrow-band imaging (NBI) and autofluorescence imaging (AFI) enable SESCC to be easily visualized without LCE. This study aimed to assess the visualizing power of white-light imaging (WLI), NBI, and AFI, compared with LCE. Sixteen patients with 16 SESCCs underwent LCE and endoscopy with NBI and AFI before endoscopic or surgical treatment. Twenty sets of endoscopic SESCC images were prepared, each of which contained still images from WLI, NBI, AFI, and LCE. The image sets were shown to 25 endoscopists, who then each completed a questionnaire about the ease-of-detection of the SESCCs, scoring WLI, NBI, and AFI images with reference to a perfect score for LCE; mean scores were compared. Overall, significantly higher scores were given for NBI than for WLI and AFI, with no significant difference between WLI and AFI. Stratification by endoscopist characteristics indicated that younger or less experienced endoscopists gave significantly higher scores for AFI than WLI. Stratification by lesion characteristics revealed that AFI had significantly higher scores than WLI for flat/elevated lesions or those with diameter ≥20 mm; scores were significantly lower for depressed lesions or those with diameter <20 mm. For SESCC, the visualizing power of NBI seems more similar to that of LCE than AFI or WLI: NBI might be more useful than AFI or WLI in detecting SESCC. AFI seems to have both superior and inferior visualizing power to WLI depending on characteristics of endoscopists or SESCC lesions.     

Chromoendoscopy is a valuable tool for screening of high-risk patients with head and neck cancer for early detection of esophageal cancer

BACKGROUND: The incidence of esophageal cancer is markedly increased in patients with head and neck cancer, and the presence of esophageal cancer is associated with reduced survival rates. AIMS: We investigated whether the results of screening for esophageal cancer in patients with head and neck cancer using chromoendoscopy would change the treatment of such patients. PATIENTS: 87 patients with head and neck cancer and known alcohol or nicotine abuse were screened for esophageal cancer. Methods: The patients underwent esophagogastroduodenoscopy and staining of the esophagus with 2% Lugol's solution. Biopsies were taken from unstained areas for histopathological assessment. RESULTS: Esophageal cancer was newly diagnosed in 10 patients (11.5%), including 2 with carcinoma in situ. There were dysplastic changes in 6 patients (7%) and an unknown Barrett esophagus in 4 patients (5%). In 36 patients (41%) unstained areas were associated with esophagitis. While unstained areas could not be detected in 17 patients, the histology was normal in 14 patients with unstained areas. In all the patients with newly detected invasive esophageal cancer, the treatment had to be changed from a curative neoadjuvant approach to palliative treatment. In 2 patients with carcinoma in situ mucosectomy was performed. In the cases with dysplastic areas and newly detected Barrett epithelium a careful follow-up regime was arranged. CONCLUSIONS: The staging of patients with head and neck cancer, and the risk factors for esophageal cancer should include chromoendoscopy of the esophagus as a standard procedure. Extended staging provides critical additional information, which helps to more safely distinguish future candidates for curative and palliative treatment.     

Telomerase activity in esophageal squamous cell carcinoma and lesions unstained with Lugol's solution

BACKGROUND/AIMS: Telomerase is a ribonucleoprotein enzyme that protects erosion of telomeres at the ends of chromosomes and its activity has been detected in immortalized cells and most human cancers. METHODOLOGY: We analyzed telomerase activity in primary esophageal squamous cell carcinomas (SCCs) without any preoperative treatment and lesions unstained with Lugol's solution, using a telomeric repeat amplification protocol (a TRAP) assay. RESULTS: Strong telomerase activities were detected in all resected specimens of esophageal SCCs, and in 33 of 40 endoscopic biopsy specimens of lesions unstained with Lugol's solution. Among lesions unstained with Lugol's solution, 19 of 19 esophageal SCCs, and 13 of 13 dysplasias, which are considered as clinically precancerous lesions had strong telomerase activities. CONCLUSIONS: These results indicate that reactivation of telomerase may occur at an early stage in the carcinogenesis of esophageal SCCs, and telomerase activity may be a practically useful molecular biological marker for supporting the diagnosis of early esophageal SCCs.     

Metachronous squamous cell carcinoma of the esophagus arising after endoscopic mucosal resection

BACKGROUND: Endoscopic mucosal resection (EMR) is being used increasingly to treat early stage esophageal carcinoma. However, the preserved esophageal mucosa may be the source of new lesions. The aims of this study were to analyze the frequency of metachronous esophageal carcinoma after EMR and to determine whether minute iodine unstained areas often associated with squamous cell carcinoma develop into carcinoma. METHODS: Eighty-two patients with esophageal squamous cell carcinoma who underwent EMR were studied. Based on the iodine staining pattern at initial EMR, they were divided into those with uniform (group U) and scattered (group S) types of background mucosa. Patients were followed by endoscopy with iodine staining (group U: median 39 months, range 12 to 71 months; group S: median 38 months, range 14 to 68 months). RESULTS: In total, 12 (14.6%) of 82 patients were found to have metachronous esophageal carcinoma during follow-up, including 6 (37.5%) of 16 patients in group S. The cumulative proportion of metachronous carcinoma-free subjects was significantly lower in group S than group U (p = 0.0048). CONCLUSIONS: Primary esophageal carcinoma develops frequently in patients who have undergone EMR for esophageal squamous carcinoma. The high frequency of metachronous carcinoma may be attributed to field carcinogenesis. Careful long-term endoscopic observation is required for patients who undergo EMR for esophageal carcinoma, especially those with scattered-type iodine staining of the background mucosa.     

Intraoperative endoscopy in obstructive hypopharyngeal carcinoma

AIM: To demonstrate the necessity of intraoperative endoscopy in the diagnosis of secondary primary tumors of the upper digestive tract in patients with obstructive hypopharyngeal carcinoma. METHODS: Thirty-one patients with hypopharyngeal squamous cell carcinoma had been operated, with radical intent, at our Institution in the period between 1978 and 2004. Due to obstructive tumor mass, in 7 (22.6%) patients, preoperative endoscopic evaluation of the esophagus and stomach could not be performed. In those patients, intraoperative endoscopy, made through an incision in the cervical esophagus, was standard diagnostic method for examination of the esophagus and stomach. RESULTS: We found synchronous foregut carcinomas in 3 patients (9.7%). In two patients, synchronous carcinomas had been detected during preoperative endoscopic evaluation, and in one (with obstructive carcinoma) using intraoperative endoscopy. In this case, preoperative barium swallow and CT scan did not reveal the existence of second primary tumor within esophagus, despite the fact that small, but T2 carcinoma, was present. CONCLUSION: It is reasonable to use intraoperative endoscopy as a selective screening test in patients with obstructive hypopharyngeal carcinoma.     

Advances in esophageal imaging: practical applications for clinicians

In the 1960s, the revolution in the diagnosis and management of gastrointestinal diseases began with the introduction of the first flexible fiber endoscope. Since then, the technologies have evolved greatly. Particularly in recent years, much emphasis has been placed on developing new gastrointestinal endoscopy technologies or techniques in order to provide a precise and even a "real time" endoscopic diagnosis. Magnification and high-resolution endoscopy, chromoendoscopy, and narrow band imaging stand at the forefront of the novel endoscopic techniques for the diagnosis of conditions such as squamous cell carcinoma, Barrett's esophagus, and gastroesophageal reflux disease. This review summarizes the recent advances in esophageal imaging and its practical applications for clinicians.     

Alcohol consumption as a major risk factor in the development of early esophageal cancer in patients with head and neck cancer

OBJECTIVE: To clarify the incidence of concomitant esophageal cancers in patients with head and neck cancer (HNC), and to investigate which risk factors are responsible for this association. PATIENTS AND METHODS: From 1994 to 2000, 134 patients with HNC underwent upper gastrointestinal endoscopy using the 0.8% Lugol stain method to detect esophageal cancer. A case-control study was designed to compare HNC patients with and without esophageal cancer. Logistic-regression analysis was used to obtain odds ratios of risk factors. RESULTS: Out of 134 patients with HNC, Lugol unstained area was detected in 42 patients. Biopsy specimens revealed squamous cell carcinoma in 17 (12.7%), dysplasia in 9 patients (6.6%), and normal in the others. Gastric carcinoma was also detected in 7 patients (5.2%). The estimated depth of cancer invasion was mucosa in 9 patients, submucosa in 5 patients, and proper muscle or deeper in 3 patients. In the results of statistical analysis, high alcohol consumption of more than 75 g per day increased the risk of esophageal cancer (odds ratio: 20.2, p<0.01). Intake of hard liquor showed a high odds ratio (whisky: 28.7, p<0.05, shochu: 12.7, p<0.05). The amount of cigarette smoking was not related to this association. CONCLUSION: High incidence of esophageal cancer was found in the patients with HNC. A high alcohol consumption level, and in particular hard liquor, participated in the development of esophageal cancer in the patients with HNC. But cigarette smoking was not related to this association.