Early Detection Of Esophageal Cancer Research Articles

Finding Pink Discoloration (“Pink Panther”) Among “Panther Patches” On Esophageal Iodine Stain Leads to Detection of Early Esophageal Cancer

Aim: Esophageal cancer is common in patients with a history of head and neck cancer and/or patients with a habit of drinking and smoking. Early detection of esophageal cancer enables endoscopic therapy of the cancer. However, it is often difficult to detect early esophageal cancer on conventional endoscopic observation. Iodine stain of the esophageal mucosa has been developed to detect cancer based on the difference of stainability with iodine between normal esophageal mucosa and cancer. Normal esophageal mucosa contains abundant glycogen, which is stained dark-brown with iodine. Thus areas unstained with iodine have a good chance to be a cancer. But some patients present with multiple and diffuse unstained areas on iodine stain (Panther patches). It is not practical in these patients to perform histological evaluation on every unstained area. We noticed that some unstained areas on iodine stain appeared pink during the period when the dark brown color gradually faded. An aim of this study is to evaluate the predictability of this area to be a cancer. Patients & Methods: We reviewed retrospectively upper GI endoscopy records of the Cancer Institute Hospital for the recent 21 months. Out of 15,000 patients who underwent upper GI endoscopy, 1,975 were examined for esophagus in detail using 1.5% iodine solution to detect esophageal cancer. Results: Esophageal mucosa stained with iodine showed “Panther patches” in 125 patients. Among them, pink discoloration (Pink panther) was visible in 20 patients during the period when dark-brown stain gradually fading. Histological evaluation of those 20 patients revealed that 12 (60%) had squamous cell carcinoma, 7 (35%) had dysplasia, and 1 (5%) had inflammation. Discussion: Iodine stain is a good method to detect early esophageal cancer. However, a number of patients present with multiple unstained areas on iodine stain. Pink discoloration may reflect the increased blood flow of the cancer. Conclusion: Finding a pink panther among panther patches on esophageal iodine stain leads to detection of early esophageal cancer.

Ataxia‐telangiectasia mutated expression is associated with tobacco smoke exposure in esophageal cancer tissues and benzo[a]pyrene diol epoxide in cell lines

Esophageal cancer is a substantial health problem because of its usually late stage at diagnosis and poor prognosis. Tobacco smoking and alcohol use are the most important risk factors in the development of esophageal squamous cell carcinoma (SCC). Our previous study demonstrated the binding of benzo[a]pyrene diol epoxide (BPDE), a carcinogen present in tobacco smoke and environmental pollution, to the ataxia-telangiectasia mutated (ATM) gene. To understand how this binding affects the alteration of ATM expression and to identify biomarkers for the detection of esophageal cancer, we analyzed ATM mRNA expression in tissue specimens from patients with esophageal SCC and premalignant lesions using in situ hybridization. We then performed in vitro experiments to verify and extend our ex vivo observations. We found that ATM expression was increased in esophageal SCC and its premalignant lesions when compared with normal tissues and that increased ATM expression was associated with tobacco smoke exposure and tumor de-differentiation. Moreover, BPDE induced ATM expression in esophageal SCC cell lines in a time-dependent manner. In summary, the BPDE in tobacco smoke may be responsible for increased ATM expression in premalignant and malignant esophageal tissues. Our findings suggest that the ATM gene should be further evaluated as a biomarker for the early detection of esophageal cancer and tobacco use in patients.

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.

Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin

Recent advances in two-dimensional electrophoresis (2-DE) such as fluorescent 2-D differential gel electrophoresis (2-D DIGE) has made it possible to detect and quantitate the critical changes involved in disease pathogenesis. We have previously identified novel proteins with altered expression in primary colorectal cancer using agarose 2-DE that has a higher loading capacity than immobilized pH gradient gel. The aim of this study is to identify novel proteins with altered expression in primary esophageal cancer using the powerful method of agarose 2-DE and agarose 2-D DIGE. Excised tissues from 12 patients of primary esophageal cancer were obtained. Proteins with altered expression between cancer and adjacent non-cancer tissues were analyzed by agarose 2-D DIGE and identified by mass spectrometry. Thirty-three proteins out of 74 spots with altered expression in tumors were identified. Among them, a 195-kDa protein, periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Immunohistochemistry showed that periplakin was mainly localized at cell-cell boundaries in normal epithelium and dysplastic lesions, while it disappeared from cell boundaries, shifted to cytoplasm, in early cancers and scarcely expressed in advanced cancers. These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression.

Investigation for new biomarker of primary esophageal squamous cell carcinoma using two-dimensional differential gel electrophoresis

Recent advances in 2-D differential gel electrophoresis (2-D DIGE) have made it possible to detect and quantitate the critical changes involved in disease pathogenesis. We have identified novel proteins with altered expression in primary esophageal cancer using the powerful method of agarose 2-D DIGE. Excised tissues from 12 patients of primary esophageal cancer were obtained. Proteins with altered expression between cancer and adjacent non-cancer tissues were analyzed by agarose 2-D DIGE and identified by mass spectrometry. 2-D DIGE has many advantages on proteomic analysis for clinical specimens. 33 proteins with altered expression in tumors were identified. Among them, a 195kDa protein, periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Immunohistochemistry showed that periplakin was mainly localized at cell-cell boundaries in normal epithelium and dysplastic lesions, while it disappeared from cell boundaries, shifted to cytoplasm, in early cancers and less expressed in advanced cancers. These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor invasion, metastasis and progression.

TC21/R-Ras2 Upregulation in Esophageal Tumorigenesis: Potential Diagnostic Implications

Objectives: Early detection of esophageal cancer is hampered by paucity of molecular markers for diagnosis of this aggressive gastrointestinal malignancy in early stages. We recently identified TC21/R-Ras2, a small GTP-binding protein (SMG) in esophageal squamous cell carcinomas (ESCCs) by differential display. This study was designed to test the hypothesis that differential expression of TC21 in normal, dysplastic and malignant esophageal tissues may be of clinical relevance in esophageal tumorigenesis. Methods:Immunohistochemical analysis of TC21 was carried out in 83 ESCCs, 37 dysplasias and 29 matched histologically normal esophageal tissues and correlated with clinicopathological parameters. The cellularlocalization of TC21 was determined by confocal microscopy. Results: Expression of TC21 protein was observed in 60/83 (73%) ESCCs predominantly localized in tumor nuclei. Intriguingly, intense TC21 immunoreactivity was observed in all endoscopic biopsies with histological evidence of dysplasia (16 cases) as well as in dysplastic areas distant to ESCCs (21 cases), while matched distant histologically normal epithelia did not show detectable TC21 expression. Immunoblotting and semi-quantitative RT-PCR confirmed TC21 expression in dysplastias and ESCCs. Confocal microscopy showed nuclear as well as cytoplasmic TC21 expression in ESCCs and TE13 cells. Conclusions: To our knowledge, this is the first report demonstrating differential expression of TC21 in normal, dysplastic and ESCC tissues, suggesting that TC21 expression is associated with early stages of esophageal tumorigenesis. Nuclear localization of TC21 makes it the third of over 100 small SMGs identified to be localized in the nucleus.

Evaluation of double staining combined with endosonography in detection of early esophageal cancer and precancerous lesions

Evaluation of double staining combined with endosonography in detection of early esophageal cancer and precancerous lesions

Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer

The aim of this study was to examine how aldehyde dehydrogenase-2 (ALDH2) genotypes and human leukocyte antigen (HLA) haplotypes contribute to the risk for esophageal cancer. We examined ALDH2 genotypes and HLA haplotypes in 29 Japanese patients with esophageal cancer. The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype. The ratio of inactive ALDH2 was significantly higher in patients with esophageal cancer than in control normal subjects, suggesting that alcoholics with inactive ALDH2 were susceptible to esophageal cancer. HLA haplotypes A24, A26, B54, B61 and DR9 were prevalent in patients with esophageal cancer (82.8, 24.1, 34.5, 37.9 and 44.8%, respectively). HLA haplotype of A24 and inactive ALDH2 were simultaneously found in 58.6% of patients with esophageal cancer. Furthermore, we found other primary malignancies in 6 of 29 (20.7%) patients with esophageal cancer, and 4 of these 6 patients had both the inactive form of ALDH2 and the HLA A24 haplotype. The present study showed the high prevalence of the inactive form of ALDH2 and HLA haplotypes A24, A26, B54, B61 and DR9 in Japanese patients with esophageal cancer. Therefore, the examination of genotypes of ALDH2 loci and HLA haplotypes may allow the early detection of esophageal cancer in the Japanese population.

Endoscopic Iodine Staining for Detecting Esophageal Cancer in Patients with Other Primary Cancers

Early detection of esophageal cancer is key for improving prognosis and survival. Some research has shown an association between squamous cell cancer

Endoscopic mucosal resection for early esophageal cancer

In the United States and Europe, the focus of endoscopic treatment for esophageal cancer has been the palliative management of advanced cancers. In Japan, where cancers of the esophagus and stomach have a high prevalence, the focus has been the early detection of esophageal cancer and the development of endoscopic modalities to curatively treat cancer. Advances in the endoscopic and endosonographic diagnosis of early esophageal cancer have paralleled the development of endoscopic resectional techniques, collectively referred to as endoscopic mucosal resection (EMR). EMR has achieved a high level of sophistication in Japan, where endoscopists use double-lumen endoscopes, specia overtubes, and innovative accessories to achieve complete and safe excision of early esophageal cancer. In appropriately selected patients, EMR offers an attractive alternative to conventional surgical management. Interest for EMR techniques is growing in the United States and Europe as a result of increased awareness of early cancer and the potential for cure endoscopically.

Survival Benefit of Screening for Early Esophageal Carcinoma in Head and Neck Cancer Patients

Abstract: Primary cancer of the head and neck was diagnosed in 676 cases. Systematic endoscopic screening of the upper gastrointestinal tract (including iodine staining of the esophagus) was performed within 1 month of diagnosing head and neck cancer in order to determine the possible presence of a second malignancy‐ We divided cases in which esophageal cancer was detected into a group in which the initially diagnosed head and neck cancer had been treated curatively and those in which the treatment had been non‐curative. A pathological diagnosis of primary esophageal cancer was obtained in 37 cases (5.5%). The incidence of esophageal cancer associated with cancer of the oral cavity or pharynx was significantly higher (10.9%) than in cases with an associated cancer of the larynx or paranasal sinus (1.9%, p<0.05). All but one of the 37 cases detected by screening were asymptomatic and had superficial carcinoma. Of these lesions, 19 Were mucosal carcinomas, 17 submucosal carcinomas and only one an advanced cancer. Twenty‐four of these 37 cases had died. The cause of death was head and neck cancer in 17, esophageal cancer in two and other causes in five. The 5‐year survival rate of cases in whom the initial head and neck cancer had been treated curatively was 46.7%.The risk of synchronous esophageal cancer associated with cancer of the head and neck is high. Early detection of esophageal cancer at the time of diagnosing cancer of the head and neck and treatment at an early stage is a new strategy for improving the long‐term outcome of cases with head and neck cancers associated with esophageal cancer.

Endoscopic detection of early esophageal cancer in a high-risk population: does Lugol staining improve videoendoscopy?

Background: The aim of this study was to prospectively compare the diagnostic accuracy of videoendoscopy, with and without Lugol staining, for the detection of esophageal cancer in alcoholic or smoking patients older than 40 years. Methods: Daily alcohol and tobacco consumption and overt and latent symptoms were noted. The 158 patients included were examined by videoendoscopy and with Lugol dye. Results: The mean consumption of alcohol and tobacco was 86 ± 49 gm/day for 26 ± 11 years, and 30 ± 18 pack-years, respectively. Twenty-five patients had no symptoms. Before Lugol staining, 12 patients had endoscopically identified cancerous lesions. After Lugol staining, 13 patients had 17 esophageal cancers, 3 of which were high-grade dysplasia. The prevalence of esophageal cancer was 8.2%: 95% CI [4,14]. Dye-free surfaces were significantly larger than the endoscopic patterns observed before Lugol staining (11.6 ± 9.2 cm 2 vs 1.4 ± 1.7 cm 2; p < 0.02). Conclusions: In an alcoholic smoking population, the prevalence of esophageal cancer detected by endoscopy is high and not related to symptoms described by patients. Lugol staining only moderately improves the diagnostic accuracy of videoendoscopy; its main advantage is the assessment of the mucosal extension of esophageal cancer. (Gastrointest Endosc 1997;45:480-4.)

Early detection of esophageal cancer by chromoendoscopy

Early detection of esophageal cancer by chromoendoscopy

Successful screening for early esophageal cancer in alcoholics using endoscopy and mucosa iodine staining.

Epidemiologic studies have provided evidence that alcohol abuse is an important risk factor for esophageal carcinoma. However, no systematic screening program has been established yet in the early detection of esophageal cancer in high risk populations of heavy drinkers. A cohort of 629 male alcoholics (54 +/- 8 years old) were consecutively and systematically screened by endoscopy combined with iodine staining and targeted biopsy at the National Institute on Alcoholism (Kanagawa, Japan). For mucosal carcinomas, endoscopic esophageal mucosal resection (EEMR) was used to serve confirmatory diagnostic and therapeutic purposes. Iodine-unstained lesions, distinctly demarcated, white, and 5 mm or larger in greatest dimension, were observed on the esophageal wall in 162 patients (25.8%). Thirty-six such unstained lesions in 21 of 629 patients, with an unexpectedly high rate of 3.3%, turned out to be squamous cell carcinomas of the superficial type. According to some established criteria, EEMR was performed in 17 of these patients, 3 of whom were given additional irradiation. Esophagectomy was performed in two patients, chemotherapy combined with irradiation in one, whereas still another was followed endoscopically. The cancer invasion was confined within the epithelium in eight patients, to the proper mucosal layer in nine, and to the submucosa in four. Multiple logistic regression revealed that the risks for distinct iodine-unstained lesions and superficial esophageal carcinoma increased independently for users of stronger alcoholic beverages, i.e., whiskey or shochu (odds ratio [OR] = 1.47 and 2.94, respectively) compared with lighter beverages, i.e., sake or beer and 30+ cigarettes/day (OR = 1.68 and 3.85, respectively). Routine application of this program for these high risk individuals yielded an unusually high rate of detection of esophageal carcinoma.

Endoscopic detection of early esophageal cancer in a high risk population. Does the lugol coloration improve the results of video-endoscopic examination?

Endoscopic detection of early esophageal cancer in a high risk population. Does the lugol coloration improve the results of video-endoscopic examination?

Cytologic diagnosis of oral, esophageal, and peripheral lung cancer

Oral cavity. Most carcinomas in situ of the oral cavity present as red or pink lesions that do not have a keratinized surface. Scrapings of such lesions readily disclose abnormal squamous cells diagnostic of cancer. Scrapings of the keratinized white lesions (so-called leukoplakia) are of no diagnostic value. Dentists, who are most likely to uncover precancerous lesions, are apparently not aware of the diagnostic options based on simple scrape smears. The method is also applicable to follow-up of patients with treated cancer of the oral cavity. Esophagus. Cytologic evaluation of esophageal cancer, initially by washings and subsequently by brushings under endoscopic control, is an established method of diagnosis. The diagnostic results are very good in symptomatic cancer patients and have an accuracy reaching 85-90%. Unfortunately the results of treatment of advanced lesions are very poor, with 5-year survival of only about 5%. Serious efforts at detection of early esophageal cancer started in China in the 1960s, using an abrasive balloon technique which was applied to asymptomatic populations in high risk areas such as Linxian in the Henan province of Central China. The Chinese investigators reported the finding of numerous precancerous lesions of the esophagus classified as carcinoma in situ and as dysplasia. Surgical resection of some of the precursor lesions apparently resulted in a significant drop in the rate of invasive carcinoma, although the statistical results were not convincingly presented. The balloon technique has been tested by us and by others in South Africa and in Transkei, confirming its efficacy in the diagnosis of early esophageal cancer. Peripheral lung. Sputum and bronchial brush cytology may uncover bronchogenic carcinoma in situ and early invasive cancers located in the primary or secondary bronchi. Small, peripheral lung lesions usually do not shed cells in sputum or brushings, and their discovery is usually based on roentgenologic finding. The identity of such lesions can be confirmed in most cases by a transcutaneous aspiration. Most of the peripheral malignant lesions are small adenocarcinomas or epidermoid carcinomas, both resectable by routine surgical procedures. Less commonly, oat cell carcinomas may be observed and these lesions should not be treated by surgery. Benign lesions such as granulomatous inflammation and fungal infections may also be identified by aspiration techniques. The prognosis of the resectable carcinomas varies with their size and the presence or absence of regional lymph node metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Natural history and significance of esophageal squamous cell dysplasia

Balloon-mesh cytologic screening for esophageal cancer done in 255 asymptomatic high-risk United States veterans (age greater than 40 years, ethanol abuse for greater than 20 years, and cigarette smoking greater than 20 pack years) identified 37 patients with squamous cell dysplasia. Of the 37 patients with dysplasia, 28 were re-evaluated prospectively at 6-month intervals for up to 36 months by balloon-mesh cytology, esophagoscopy with vital staining and biopsies, chest radiographs, oropharyngeal examination, and indirect laryngoscopy. During prospective follow-up evaluation, cytology specimens were repetitively normal in 16 patients (57%), showed inflammatory changes in eight patients (29%), persisted as dysplasia in two patients (7%) (both had endoscopic and histologic evidence of esophagitis), and progressed to carcinoma in two patients (7%) (one esophageal, one laryngeal). Although histologic findings concurred with the resolution of dysplasia, biopsy specimens were characterized by a similar difficulty in distinguishing dysplasia from inflammation. Erroneous histologic diagnoses of carcinoma in situ were made in two patients with reflux esophagitis evident endoscopically and confirmed during the course of a 24-36 month follow-up period. The authors conclude that squamous cell dysplasia detected by balloon-mesh cytology is seldom a precursor of esophageal cancer in the high-risk U.S. population but, rather, is often related to esophagitis. Thus, balloon-mesh cytology has limited use as a screening method for the early detection of esophageal cancer in the United States.