Exploring contrast-enhancing staining agents for studying adipose tissue through contrast-enhanced computed tomography.

Contrast-enhanced computed tomography offers a nondestructive approach to studying adipose tissue in 3D. Several contrast-enhancing staining agents (CESAs) have been explored, whereof osmium tetroxide (OsO4) is the most popular nowadays. However, due to the toxicity and volatility of the conventional OsO4, alternative CESAs with similar staining properties were desired. Hf-WD 1:2 POM and Hexabrix have proven effective for structural analysis of adipocytes using contrast-enhanced computed tomography but fail to provide chemical information. This study introduces isotonic Lugol's iodine (IL) as an alternative CESA for adipose tissue analysis, comparing its staining potential with Hf-WD 1:2 POM and Hexabrix in murine caudal vertebrae and bovine muscle tissue strips. Single and sequential staining protocols were compared to assess the maximization of information extraction from each sample. The study investigated interactions, distribution, and reactivity of iodine species towards biomolecules using simplified model systems and assesses the potential of the CESA to provide chemical information. (Bio)chemical analyses on whole tissues revealed that differences in adipocyte gray values post-IL staining were associated with chemical distinctions between bovine muscle tissue and murine caudal vertebrae. More specific, a difference in the degree of unsaturation of fatty acids was identified as a likely contributor, though not the sole determinant of gray value differences. This research sheds light on the potential of IL as a CESA, offering both structural and chemical insights into adipose tissue composition.

Persistence of Lugol-unstaining is Associated With an Increased Risk of Progression to Malignancy in the Esophagus.

BACKGROUND & AIMS: The aim of this study was to investigate the persistence of Lugol-unstained lesions (LULs) in the esophagus detected by chromoendoscopy and explore their association with progression to malignancy. METHODS: We enrolled 647 participants from a population-based screening trial who had biopsied LULs at the baseline chromoendoscopy and underwent a chromoendoscopy re-examination after a median of 4.39 years. Cases of persistent LUL were defined as those in whom a visible LUL was observed during re-examination at the documented location (±2 cm) where a LUL was detected at baseline chromoendoscopy. Logistic regression was applied to explore risk factors for the persistence of LULs. The primary outcome was clinical-stage esophageal squamous cell carcinoma identified over 6.78 years of follow-up, and the secondary outcome was re-examination-detected severe dysplasia and above lesions. The cumulative incidence was calculated to assess the progression risk associated with the persistence of LULs. RESULTS: The proportion of participants with persistent LULs was 81.92%. Dysplasia (adjusted odds ratio [OR], 6.16; 95% confidence interval [CI], 2.70-17.80), large LULs (adjusted OR, 1.90; 95% CI, 1.18-3.15), and irregularly shaped LULs (adjusted OR, 1.63; 95% CI, 1.03-2.56) at baseline were associated with an increased risk of LUL persistence. Eleven clinical-stage esophageal squamous cell carcinoma cases and 31 severe dysplasia and above lesions detected during reexamination were identified, all of which originated from patients with persistent LULs (Pclinical-stage ESCC = .136; Pre-examination-detected SDA = .015). CONCLUSION: The persistence of LULs is associated with progression to malignancy in the esophagus, even in individuals without dysplastic lesions. Based on this, a more efficient post-screening surveillance strategy could be established.

Efficacy of endoscopic surveillance for pharyngeal mucosa during endoscopic resection for pharyngeal carcinoma: a multicenter prospective study.

INTRODUCTION: Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). METHODS: From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. RESULTS: Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. CONCLUSIONS: Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.

Contrast-Enhanced Micro-CT Imaging of Murine Mandibles: A Multi-Method Approach for Simultaneous Hard and Soft Tissue Analysis.

AIM: To develop and evaluate a novel multi-method micro-computed tomography (µCT) imaging protocol for enhanced visualization of both hard and soft tissues in murine mandibles, addressing the limitations of traditional imaging techniques in dental research. MATERIALS AND METHODS: We employed a contrast-enhanced (CE) µCT imaging technique using Lugol's iodine as a contrast agent to visualize the intricate structures of murine mandibles. The protocol involved the combination of conventional µCT imaging as well as CE-µCT, including decalcification with EDTA, allowing for simultaneous assessment of hard and soft tissues. The method is compared with standard imaging modalities, and the ability to visualize detailed anatomical features is discussed. RESULTS: The CE-µCT imaging technique provided superior visualization of murine mandibular structures, including dental pulp, periodontal ligaments and the surrounding soft tissues, along with conventional µCT imaging of alveolar bone and teeth. This method revealed detailed anatomical features with high specificity and contrast, surpassing traditional imaging approaches. CONCLUSION: Our findings demonstrate the potential of CE-µCT imaging with Lugol's iodine as a powerful tool for dental research. This technique offers a comprehensive view of the murine mandible, facilitating advanced studies in tissue engineering, dental pathology and the development of dental materials.

Is blue light imaging without magnification satisfactory as screening for esophageal squamous cell carcinoma? Post-hoc analysis of multicenter randomized controlled trial.

OBJECTIVES: Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC. METHODS: This was a post-hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE. RESULTS: This study identified ESCC in 49 of 699 cases. Of these cases, nine (18.4%) were missed by BLI but detected by LCE. In per-patient analysis, the sensitivity of BLI was lower than that of LCE following BLI (83.7% vs. 100.0%; P = 0.013), whereas the specificity and accuracy of BLI were higher (88.2% vs. 81.2%; P < 0.001 and 87.8% vs. 82.5%; P < 0.001, respectively). No significant endoscopic characteristics were identified, but the color difference was lower in BLI than in LCE (21.4 vs. 25.1; P = 0.003). CONCLUSION: LCE following BLI outperformed BLI in terms of sensitivity in patients with high-risk ESCC. Therefore, LCE, in addition to BLI, would still be required in screening esophagogastroduodenoscopy even by expert endoscopists.

Association between continuous cessation or reduction of drinking alcohol and improvement of multiple dysplastic lesions in patients with esophageal squamous cell carcinoma after endoscopic resection.

BACKGROUND: Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. METHODS: We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6 months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6 months. RESULTS: Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009). CONCLUSIONS: This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. CLINICAL TRIALS REGISTRY NUMBER: UMIN000001676.

Routine image-enhanced endoscopic surveillance for metachronous esophageal squamous cell neoplasms in head and neck cancer patients.

BACKGROUND: Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy. METHODS: From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed. RESULTS: A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs. CONCLUSIONS: IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality.

Optimal concentration of Lugol's solution for detecting early esophageal carcinoma: A randomized controlled trial.

BACKGROUND AND AIM: Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. METHODS: This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. RESULTS: In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005). CONCLUSIONS: The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).

Lugol's solution and Gentian violet eradicate methicillin-resistant Staphylococcus aureus biofilm in skin wound infections.

The study aimed to evaluate the antibacterial efficacy of Lugol's solution 5% and Gentian violet 1% against methicillin-resistant Staphylococcus aureus (MRSA) biofilm in vivo. The bactericidal efficacy for treatment of MRSA-biofilm skin wound infection was tested in a murine model. Luciferase-tagged S. aureus Xen31, a MRSA-strain derived from S. aureus ATCC-3359130, was used for infection. Wounds were made in the skin of mice and infected with MRSA. The mice were treated with Lugol's solution and Gentian violet. Application of the antimicrobial agents started 24 hours post infection and was repeated daily for five-days. The antimicrobial effect on the biofilm bacteria was evaluated by measuring bioluminescence from MRSA daily for seven-days. Lugol's solution and Gentian violet showed a significant reduction in luminescent signals from the first assessment day to all subsequent days (P < .001). Lugol's solution and Gentian violet effectively eradicated MRSA in biofilm in vivo and could be alternatives or in addition to topical antibiotics when MRSA-biofilm wound infection is suspected.

Severe autoimune thyreotoxicosis complicated by febrile neutropenia as a result of thyreostatic therapy.

Hyperthyreoidism is a clinical manifestation of excessive production of thyroid hormones. In most cases pacient ´s condition allows ambulant treatment. Rarely, it can develop into an acute, life- threatening thyrotoxic crisis which has to be treated in the intensive care unit. Main therapy includes antithyroid medication, corticosteroids, beta- blockers and rehydratation, mostly parenteral. If initial treatment fails, plasmapheresis provides effective strategy. Antithyroid medication may come with side effects as rash, digestive issues, joint pain.Agranulocystosis or acute liver lesion which leads to liver failure belong among the most severe ones. In this case we report a pacient with thyrotoxic crisis, atrial fibrilation which led to ventricular fibrilation, cor thyreotoxicum. The treatment was complicated by febrile neutropenia.

A quantitative assay for agarase activity determination using agarose-iodine complex.

Rapid and simple spectrophotometric methods are required to detect various oligosaccharides produced by agar-hydrolysing enzymes. Herein, we present a quantitative agarose-iodine assay for agarase activity determination via the detection of the extent of agarose degradation. The agarose-iodine complex becomes reddish orange upon the addition of Lugol solution, and the enzymatic activity can be detected with ultraviolet-visible spectroscopy at 600 nm. The main advantages of this modified Lugol assay are high sensitivity, simple detection, and cost effectiveness. A novel definition of the unit to measure and compare the activities of agarases is also suggested.

Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in Taiwan.

BACKGROUND: Endoscopic submucosal dissection (ESD) is gradually turning into the standard treatment for superficial esophageal squamous cell carcinoma (SESCC), however, the long-term outcomes have hardly ever been reported outside Japan. METHOD: We consecutively recruited patients with SESCC who had received ESD treatment at E-Da Hospital. The demographics, pathological characteristics, and Lugol staining background pattern (type A or B: none or < 10 small Lugol-voiding lesions [LVLs]; type C or D: > 10 small or multiform LVLs) were collected, and then correlated to outcomes and survival. RESULTS: Total of 229 lesions were enrolled and the mean lesion size was 3.28 ± 1.69 (range 1-10) cm. 72% of the lesions had a type C-D Lugol staining background pattern. After ESD, the en bloc and R0 resection rates were 93.9% and 83.5%, respectively. Forty-nine subjects developed complications, including six (2.6%) with major bleeding, two (0.9%) with perforation, and 41 (17.9%) with strictures. Pathological staging showed that 19 cases had deep submucosal cancer invasion and subsequently received adjuvant therapies. During a mean follow-up period of 52.6 (range 3-146) months, 41 patients developed metachronous recurrence. The patients with a type C-D Lugol staining background pattern were associated with a higher risk of recurrence than those with few LVLs (log-rank P = 0.019). The 10-year survival rate was more than 90%, and only eight patients died of ESCC. CONCLUSION: ESD has excellent long-term outcomes but a high risk of metachronous recurrence. The Lugol staining pattern over the background mucosa could offer the risk stratification of metachronous recurrence.

Effectiveness of Chemoradiotherapy for Metachronous Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Multiple Lugol-voiding lesions (LVLs) in the esophagus increase the risk of synchronous and metachronous development of esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) following endoscopic submucosal dissection (ESD) may reduce the incidence of metachronous ESCC, but few studies have investigated this. Therefore, we retrospectively examined the effect of CRT on metachronous ESCC and multiple esophageal dysplasias visible as multiple LVLs. METHODS: This study reviewed 146 patients who underwent esophageal ESD and were determined pathologically to have noncurative resection. They were divided into 2 groups: those who received additional CRT (CRT group; n = 64) and those without additional treatment (control group; n = 82). Incidence of metachronous ESCC was analyzed using propensity scores to adjust for patient characteristics. The number of multiple LVLs was also examined. RESULTS: The CRT group was significantly younger than the control group (mean 66.6 vs. 70.6 years, p = 0.011), had significantly deeper tumor invasion (p = 0.013), and had a significantly higher rate of lymphovascular invasion (47.8 vs. 12.2%, p < 0.001). The CRT group also had a significantly higher improvement rate of multiple LVLs (58.1 vs. 2.0%, p < 0.001). The LVLs after CRT had a distinctive irregular crack-shaped appearance. Metachronous ESCC was found in 7 patients (10.9%) in the CRT group and in 17 patients (20.7%) in the control group (p = 0.113). In propensity score-adjusted logistic regression analysis, the odds ratio for metachronous ESCC in the CRT group was 0.316 (p = 0.023). The occurrence rate was significantly lower in the CRT group than in the control group. DISCUSSION/CONCLUSION: CRT may be effective in preventing metachronous ESCC.

Clinical application of the 2011 IFCPC colposcope terminology.

BACKGROUND: Colposcopy offers an accurate way to the diagnose of cervical precancerous lesions. However, the diagnostic accuracy of colposcopy is unsatisfied. This study was to evaluate colposcopic accuracy according to the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) terminology. METHODS: A retrospective cohort study was performed in 1,838 patients who underwent colposcopy in Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University from October 2013 to April 2018. Using conization or cervical biopsy pathology as the gold standard, the agreement between colposcopic diagnosis and pathologic diagnosis was calculated, and correlations between variables were analyzed. RESULTS: As an authoritative and widely used terminology for colposcopy diagnosis, the 2011 IFCPC terminology has certain clinical practicality and diagnostic accuracy. However, some signs such as mosaic, punctation, sharp border, inner border sign and ridge sign had high specificity but unsatisfactory sensitivity, which limited the diagnostic value. Therefore, we discussed the Lugol's staining, a very common sign in colposcopy, and analyzed the diagnostic significance of bright yellow staining in low-grade squamous intraepithelial lesion (LSIL) and mustard yellow staining in high-grade squamous intraepithelial lesion (HSIL). The results showed that mustard yellow may be a valuable indicator in the diagnosis of HSIL. CONCLUSION: The 2011 IFCPC colposcope terminology has standardized interpretations of the colposcopic findings and improved the accuracy of colposcopy diagnosis. The aceto-white epithelium still has important diagnostic value; however, the value of a few signs is needed to be discussed and new signs are expected to be discovered. Although the significance of Lugol's staining was diminishing, mustard yellow might be a valuable indicator for the diagnosis of HSIL.

Screening for synchronous esophageal second primary tumors in patients with head and neck cancer.

Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC.

Contrast-enhanced micro-CT to assess dental pulp tissue debridement in root canals of extracted teeth: a series of cascading experiments towards method validation.

AIM: To validate a new method for the evaluation of pulp tissue debridement in the root canals of extracted teeth using an impregnation protocol involving potassium triiodide, a radiocontrast solution known as Lugol's, combined with micro-computed tomographic (micro-CT) imaging. METHODOLOGY: The impact of NaOCl on the radiopacity of Lugol's solution was assessed using a two-fold dilution series of Lugol in distilled water and 5.25% NaOCl, which were then pipetted into transparent dishes and radiographed. To verify the influence of Lugol on the proteolytic effect of NaOCl, a dissolution test was performed using fresh bovine meat. Ten slices did not undergo any tissue processing, whilst twenty slices were fixed in formaldehyde for 24 h. After that, 10 of them were immersed in Lugol for another 24 h. Then, all specimens were placed in NaOCl and the time required for a complete tissue dissolution was recorded. For the last experiments (histological validation and micro-CT assessment), 8 extracted mandibular premolars with formerly vital pulps were immersed in buffered formalin, scanned in a micro-CT device, accessed, immersed in Lugol for 7 days and scanned again. Then, the root canals of 5 teeth were prepared and scanned, and the volume of remaining pulp tissue identified and quantified, whilst 3 teeth were histologically processed. The same specimens were subjected to histological assessment, and the images of the histologic sections were registered with the corresponding micro-CT images to verify whether the pulp tissue in the histological sections matched its counterpart in the Lugol-impregnated tissues identified in the micro-CT slices. RESULTS: There was no discernible effect on radiopacity when NaOCl was mixed with Lugol's solution. Tissue processing did not affect the time required for the complete dissolution of fresh bovine meat. Histological evaluation revealed a correlation between micro-CT and histological images confirming the identification of Lugol-impregnated pulp tissue in micro-CT images. CONCLUSIONS: The radiocontrast Lugol's solution was unaffected by NaOCl and did not interfere with its soft tissue dissolution capability. The impregnation protocol using Lugol's solution allowed the visualization of pulp tissue on the micro-CT images and the identification of pulp remnants after chemical-mechanical canal procedures.

Delineating the extent of esophageal squamous cell carcinoma.

BACKGROUND: Lugol chromoendoscopy has been conventionally used for the detection and delineation of esophageal squamous cell carcinoma (SCC). However, the boundaries of some lesions are unclear even with Lugol chromoendoscopy, and there is a risk of residual lesions or over-excision. This study aimed to evaluate the utility of narrow-band imaging (NBI) for the delineation of esophageal SCC in endoscopic resection. METHODS: Among 367 esophageal SCCs endoscopically resected between January and December 2019 at our institute, this retrospective study included consecutive lesions, which were first marked with NBI, followed by Lugol chromoendoscopy. The proportion of residual cancer, which was defined as histologically proven cancer confirmed adjacent to the scar within 1 year after endoscopic resection, was evaluated. To evaluate whether the marks added by Lugol chromoendoscopy after NBI marking were more reliable, we evaluated the presence of cancer in the iodine-unstained area outside the NBI-determined marks, i.e., the cancerous area missed by NBI. The presence of cancer in the iodine-stained areas inside the NBI-determined marks, i.e., the cancerous area missed by Lugol, was also evaluated. These were compared to assess the risk of residual cancer in endoscopic resection with NBI and Lugol chromoendoscopy. RESULTS: Among 304 lesions, 2 (0.7%) residual cancers were detected. The cancerous area missed by NBI and the cancerous area missed by Lugol were identified in 18 (6%) and 43 (14%) lesions, respectively (P = 0.001). CONCLUSIONS: NBI might be acceptable for delineating the extent of esophageal SCCs that are difficult to delineate with Lugol chromoendoscopy.

Composition and consistence of the bacterial microbiome in upper, middle and lower esophagus before and after Lugol's iodine staining in the esophagus cancer screening.

BACKGROUND: Esophageal bacteria, as the integral composition of human ecosystem, have been reported to be associated with esophageal lesions. However, few studies focus on microbial compositions in different esophageal segments, especially after Lugol's iodine staining (LIS) in the endoscopic examination for the screening of esophageal cancer. We aim to investigate the composition of the bacterial microbiome in upper, middle and lower esophagus and if LIS would affect the detection of bacteria. METHODS: A total of 141 fasting samples including the upper, middle and lower esophagus from 27 participants were collected by brushing the mucosal surface of the esophagus before (Eso) and after (Lug) LIS. Bacterial V3-V4 region of 16S rRNA gene was amplified and sequenced by Illumina's sequencing platform. RESULTS: The top six abundant bacterial phyla taxa among three locations from both Eso and Lug groups were Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and TM7. In terms of genera, the bacterium in three locations from two groups was all characterized by a highest relative abundance of Streptococcus. Bacteria diversity and the relative abundance between Eso and Lug were comparable (p > .05). Bacteria diversity was consistent in different esophageal locations within the individual. CONCLUSION: The bacterial microbiome in healthy esophagus are highly diverse and consistent even among three physiological sites at all clades. Lugol's iodine staining would not change local microenvironment in term of microbial composition. These findings provide an essential baseline for future studies investigating local and systemic bacterial microbiome and esophageal diseases.

The Value of Virtual Chromoendoscopy in the Workup of Patients with Head and Neck Squamous Cell Carcinoma.

PURPOSE OF REVIEW: Second primary tumors (SPTs) significantly increase the mortality in patients with head and neck squamous cell carcinomas (HNSCCs). Virtual chromoendoscopy (VCE) could complement or replace lugol chromoendoscopy (LCE) for early esophageal second primary tumor (ESPT) detection. An overview of the existing techniques and their diagnostic performance in early detection of esophageal squamous cell neoplasms is provided. RECENT FINDINGS: Nowadays, LCE is the golden standard to detect ESPTs. Recently, multiple new VCE techniques have been developed. Especially narrow-band imaging (NBI) is promising. It shows similar sensitivity to LCE, but a significantly higher specificity. Patients with HNSCC are prone to develop ESPTs, both synchronous and metachronous, with a substantial negative impact on survival rates. Therefore, active screening and follow-up is necessary. LCE is an effective screening method, but has some disadvantages. Countering these drawbacks, NBI shows a high potential in early ESPT detection in high-risk patients. Additional multicenter studies are needed to compare diagnostic performance and cost-effectiveness of NBI and other VCE techniques with LCE.

Association between the findings of metachronous secondary primary malignancies and the number of Lugol-voiding lesions.

This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P = 0.017 for A vs. C, P = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P < 0.0001 for trend). LVL grade C was a strong predictor of mSPM other than esophagus (RR = 3.41 for A vs. C). LVL grade may be a useful predictor of the risk of mSPM other than esophagus after ER in patients with early esophageal SCC.