Multiple Lugol-voiding Lesions Research Articles

Tu1627 Clinical Features of Metachronous Multiple Cancers in the Esophagus and Primary Cancers in the Other Organs After Endoscopic Resection for Superficial Esophageal Cancer

The outcome of patients with esophageal cancer after endoscopic resection has recently improved because of advancement in endoscopic instruments and progressive endoscopic procedures. During follow-up, it has been noted that the number of metachronous squamous cell carcinoma in the esophagus (MEsCa) or primary cancers in the other organs (MPCa) have been increasing. So the aim of this study was to clarify the clinical features of those metachronous cancers, especially at the point of association between the development of metachronous cancers and multiple Lugol-voiding lesions (mLVLs).

Natural Course of Lugol-Voiding Lesions in Patients with Superficial Esophageal Squamous Cell Carcinoma

Background: The presence of multiple Lugol-voiding lesions (LVLs) in the esophageal mucosa can indicate a high risk of esophageal squamous cell carcinoma (ESCC) as well as a diagnosis of ESCC and dysplasia. However, there have been no reports on the natural course of LVLs. Aim: This study aimed to clarify the characteristics and natural course of LVLs. Methods: Based on patients with ESCC who underwent endoscopic treatment, a retrospective study was conducted targeting 73 patients in whom the esophageal background mucosa was evaluated using Lugol staining and who were followed up for 12 months or more. LVLs were divided into groups A (none), B (several small), C (many small), and D (many irregular-shaped multiform). Results: The average follow-up period was 42.0 months. Groups A–D consisted of 13, 34, 21, and 5 patients, respectively. In group B, 3 of 34 (8.8%) patients advanced to group C. In group C, 2 of 21 (9.5%) patients advanced to group D. In total, 5 of all 73 (6.8%) patients advanced to a higher group. Conclusion: These data suggest that a risk of ESCC may obviously increase in only some of the patients by evaluation of LVLs.

Narrow band imaging for detecting superficial squamous cell carcinoma of the head and neck in patients with esophageal squamous cell carcinoma

Narrow band imaging combined with magnifying endoscopy (NBI-ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. The risk of a second primary SCC of the head and neck is very high in patients with esophageal SCC. This prospective study evaluated the detection rate of superficial SCC within the head and neck region (superficial SCCHN) with NBI-ME in patients with esophageal SCC. Between March 2006 and February 2008, 112 patients with a current or previous diagnosis of esophageal SCC were enrolled. All patients underwent endoscopic screening of the head and neck by NBI-ME. The primary end point was the detection rate for superficial SCCHN. Secondary end points were to compare demographic characteristics between patients with and without superficial SCCHN and to assess the clinical course of patients with superficial SCCHN. The detection rate for superficial SCCHN was 13 % (15/112). The prevalence of multiple Lugol-voiding lesions, observed endoscopically throughout the esophageal mucosa after application of Lugol dye solution, was significantly higher in patients with superficial SCCHN than in those without (100 % vs. 24 %, P < 0.0001). Minimally invasive curative treatment with organ preservation was feasible without severe complications in patients with superficial SCCHN after curative treatment of esophageal SCC. In patients with esophageal SCC, NBI-ME is useful for detecting superficial SCCHN, thereby facilitating minimally invasive treatment.

Characteristics of Esophageal Squamous Cell Carcinomas and Lugol-voiding Lesions in Patients With Head and Neck Squamous Cell Carcinoma

The relationship between esophageal squamous cell carcinoma (ESCC) and Lugol-voiding lesions (LVLs) in patients with head and neck squamous cell carcinoma (HNSCC) is unclear. To investigate the characteristics of ESCC and the relationship between ESCC and LVLs in patients with HNSCC. Between 2003 and 2006, 157 patients with primary HNSCC underwent Lugol chromoendoscopy at the Hiroshima University Hospital, Hiroshima, Japan. Of the patients, 135 were followed up for more than 6 months. We retrospectively analyzed the incidence of synchronous and metachronous ESCC and cumulative proportions of patients without metachronous ESCC with or without multiple LVLs. Synchronous and metachronous ESCC were detected in 17 of 157 (10.8%) and 9 of 135 (6.7%) patients, respectively. The incidence of synchronous and metachronous ESCC was significantly higher in patients with LVLs compared with the incidence in those without LVLs [13 of 32 (40.6%) vs. 4 of 125 (3.2%), P<0.0001 and 8 of 19 (42.1%) vs. 1 of 116 (0.9%), P<0.0001, respectively]. Cumulative proportions of patients without metachronous ESCC were significantly lower in patients with multiple LVLs compared with that in those without multiple LVLs (P<0.0001). Patients who had HNSCC, especially those with multiple LVLs in the esophagus, should be followed with close endoscopic observation with Lugol chromoendoscopy.

American Gastroenterological Association (AGA) Institute Technology Assessment on Image-Enhanced Endoscopy

This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute Technology Assessment on "Image-Enhanced Endoscopy." It was approved by the Clinical Practice and Economics Committee on August 3, 2007, and by the AGA Institute Governing Board September 27, 2007.

Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region

While multiple squamous cell carcinomas are often observed in the esophagus and the head and neck region and confound us about the favorable treatments, the reason why some patients are more likely to develop multiple cancers remains obscure. We statistically analyzed clinical factors in 203 patients with newly diagnosed squamous cell carcinoma, to assess the risk of multiple cancers for the establishment of an effective prevention and screening programs. Widespread epithelial oncogenic alterations were assessed as multiple lugol-voiding lesions (multiple LVL) using lugol chromoendoscopy. Genetic polymorphisms of alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2) were identified by PCR-restriction fragment length polymorphism analysis. Forty patients had synchronous multiple cancers and the remaining 163 had solitary cancer. Presence of multiple LVL was the only independent risk factor for multiple cancers [relative risk (RR) = 67; 95%CI, 15-310]. Multiple LVL was observed in only smoking drinkers. Among them, a multivariate analysis demonstrated that the ALDH2 deficiency allele (RR = 5.7; 95%CI, 2.8-11.6) and the slow metabolizing ADH3 allele (RR = 1.9; 95%CI, 1.1-7.9) were the independent risk factors for multiple LVL. Combination of these alleles lead to increase the risk of multiple LVL. In conclusion, an episode of multiple LVL is a remarkable high risk for multiple cancers both at the esophagus and the head and neck region. The interaction between drinking and the ALDH2 deficiency allele increases the risk. In addition, the slow metabolizing ADH3 allele enhances the risk. Prohibiting the use of alcohol and early detection of cancer are strongly recommended for such individuals.

Local recurrence of squamous-cell carcinoma of the esophagus after EMR

Multicentric squamous dysplasia is frequent in the esophagus and can be visualized by chromoendoscopy (Lugol's solution) as multiple Lugol-voiding lesions (LVLs). Although EMR commonly is used to treat superficial esophageal cancer, new lesions can arise and incomplete resection can result in residual disease. Little is known about the risk factors for local recurrence or the appropriate treatment for recurrent lesions. A total of 116 consecutive patients with a total of 165 esophageal squamous-cell carcinomas were studied retrospectively. Follow-up examination by means of chromoendoscopy (Lugol's solution) and biopsies was performed every 3 months during the first year after EMR and every 6 months thereafter. Lesions were defined as a local recurrence when cancer was detected at the site of the EMR scar. Risk factors associated with local recurrence were investigated by using logistic analysis. At a median follow-up of 35 months (range 12-110 months), local recurrence was detected for 33 (20%) of 165 lesions. Of the patient-related factors, multivariate logistic analysis showed that multiple LVLs (OR 3.1: 95% CI[1.1, 8.5]; p = 0.03) was an independent risk factor for local recurrence after EMR. The cumulative local recurrence rates at 3 years in patients with multiple LVLs and those without multiple LVLs were 39% and 14% (p < 0.01), respectively. All of the recurrent lesions except two could be removed by EMR, which was not associated with any serious complication. The remaining two patients had chemoradiotherapy. Overall cause-specific survival at 3 years was 100%. Patients with multiple LVLs are at risk of local recurrence after EMR. Although careful long-term endoscopic follow-up is needed for such patients, EMR is potentially curative for recurrent lesions.

Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer.

Patients with squamous-cell carcinoma in the head and neck (HNSCC) often develop second primary esophageal squamous-cell carcinomas (ESCC). In addition, widespread epithelial oncogenic alterations are also frequently observed in the esophagus and can be made visible as multiple Lugol-voiding lesions (multiple LVL) by Lugol chromoendoscopy. Multiple occurrences of neoplastic change in the upper aerodigestive tract have been explained by the concept of 'field cancerization', usually associated with repeated exposure to carcinogens such as alcohol and cigarette smoke. However, the etiology of second ESCC in HNSCC patients remains unclear and acetaldehyde, the first metabolite of ethanol, has been implicated as the ultimate carcinogen in alcohol-related carcinogenesis. We first investigated the relation between second ESCC and multiple LVL in 78 HNSCC patients. Multiple LVL and second ESCC were observed in 29 (37%) and 21 (27%) patients, respectively. All of the second ESCC were accompanied by multiple LVL. This may indicate that episodes of multiple LVL are precursors for second ESCC. We then examined the association of multiple LVL with the patients' characteristics, including genetic polymorphisms of the alcohol metabolizing enzymes, alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2). We also investigated acetaldehyde concentrations in the breath of 52 of the 78 patients. All the patients with multiple LVL were both drinkers and smokers. Multivariable logistic analysis showed that the inactive ALDH2 allele (ALDH2-2) was the strongest contributing factor for the development of multiple LVL (odds ratio 17.6; 95% confidence intervals 4.7-65.3). After alcohol ingestion, acetaldehyde in the breath was elevated to a significantly higher level in all patients with the ALDH2-2 allele than in those without it. The high levels of breath acetaldehyde were significantly modified by the slow-metabolizing ADH3-2 allele. These results reveal strong evidence for a gene-environmental interaction between the ALDH2-2 allele and alcohol consumption, for the risk of developing multiple LVL, resulting in the development of second ESCC in patients with HNSCC. Ultimately, increased local acetaldehyde exposure thus appears to be a critical determinant of the phenomenon of 'field cancerization'.

Association of multiple Lugol-voiding lesions with synchronous and metachronous esophageal squamous cell carcinoma in patients with head and neck cancer

Background: Patients with squamous cell carcinoma of the head and neck have a high prevalence of second primary esophageal squamous cell carcinomas. This study assessed the risk of developing second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck based on multiplicity of Lugol-voiding lesions observed by chromoendoscopy and patient characteristics. Methods: Three hundred eighty-nine patients with newly diagnosed squamous cell carcinoma of the head and neck were divided into 4 groups: no Lugol-voiding lesions; several (≤10) small Lugol-voiding lesions; many (>10) small Lugol-voiding lesions; and many irregularly shaped, multiform Lugol-voiding lesions. Relative risk for the development of synchronous second primary esophageal squamous cell carcinomas was investigated by using univariate and multivariate analysis. Metachronous second primary esophageal squamous cell carcinomas was also studied among 227 patients followed more than 1 year after initial examination. Results: Fifty-four (14%) of the 389 patients were found to have synchronous second primary esophageal squamous cell carcinomas. In particular, 55% of the patients with many irregular-shaped multiform Lugol-voiding lesions had synchronous second primary esophageal squamous cell carcinomas. Univariate analysis showed that the presence of many irregular-shaped multiform Lugol-voiding lesions, drinking habit, male gender, and smoking were significant risk factors for the development of synchronous second primary esophageal squamous cell carcinomas. Multivariate analysis also revealed that many irregular-shaped multiform Lugol-voiding lesions (odds ratio: 21.4; p < 0.001) and drinking habit (odds ratio: 3.3; p < 0.02) were independent risk factors. During follow-up, 7 patients (3%) had metachronous second primary esophageal squamous cell carcinomas; 6 had many irregular-shaped multiform Lugol-voiding lesions and the seventh had many small Lugol-voiding lesions in the background mucosa. Conclusions: The presence of numerous irregular-shaped multiform Lugol-voiding lesions was closely associated with second primary esophageal squamous cell carcinomas in patients with squamous cell carcinoma of the head and neck. This might be explained by the concept of “field cancerization.” Ingestion of alcohol may play an important role in the occurrence of this phenomenon. (Gastrointest Endosc 2002;56:517-21.)