Diagnosis and therapy of esophageal squamous cell dysplasia and early esophageal squamous cell cancer

Subramanian, C. R.; Triadafilopoulos, George

doi:10.1093/gastro/gox022

Cited by 9 publications

(8 citation statements)

References 73 publications

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“…According to the 2011 National Comprehensive Cancer Network (NCCN) guidelines, patients with squamous cell dysplasia (low-grade and high grade intra-epithelial neoplasm/carcinoma in situ ) and T1a where the tumor invades the lamina propria and muscularis mucosa without lymph node or vascular invasion are candidates for EET[ 13 ]. In ESSC, the risk of lymph node metastases is 0% to 6% for IMC, 8% to 30% for sm1, 30% for sm2 and 60% to 70% for sm3 cancers[ 11 , 14 - 16 ].…”

Section: Patient Selectionmentioning

confidence: 99%

Role of endoscopic therapy in early esophageal cancer

Malik

Sharma

Sanaka

et al. 2018

WJG

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Esophageal carcinoma is a highly lethal cancer associated with high morbidity and mortality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two distinct histological types. There has been significant progress in endoscopic diagnosis and treatment of early stages of cancer using resection and ablation techniques, as shown in several trials in the recent past. Earlier detection of esophageal cancer and advances in treatment modalities have lead to improvement in the 5-year survival from 5% to about 20% in the past decade. Endoscopic eradication therapy is the preferred modality of treatment in cancer limited to mucosal layer of the esophagus as there is very low risk of lymph node metastasis, leading to high cure rates, low risk of recurrence and with few adverse effects. The most common adverse events seen are strictures, bleeding and rarely perforation which can be endoscopically managed. In patients with recurrent advanced disease or invasive tumor, esophagectomy with lymph node dissection remains the mainstay of treatment. There is debate on post-endoscopic surveillance with some studies suggesting closer follow up with upper endoscopy every 6 mo for the first 1-2 years and then annually for the 3 years while others recommending the appropriate action only if symptoms or other abnormalities develop. Overall, the field of endoscopic therapy is still evolving and focus should be placed on careful patient selection using a multidisciplinary approach.

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Section: Patient Selectionmentioning

confidence: 99%

Role of endoscopic therapy in early esophageal cancer

Malik

Sharma

Sanaka

et al. 2018

WJG

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“…ESCC patients are usually diagnosed at a later stage because of lack of clinical diagnostic modalities for early diagnosis [ 27 ]. In clinical practice, the EGFR status of tumor tissues can be assessed using immunohistochemistry (IHC), which only provides limited information on target expression due to heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

PET Imaging Biomarkers of Anti-EGFR Immunotherapy in Esophageal Squamous Cell Carcinoma Models

Lee

Song

Shin

et al. 2018

Cells

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Epidermal growth factor receptor (EGFR) is overexpressed and considered as a proper molecular target for diagnosis and targeted therapy of esophageal squamous cell carcinoma (ESCC). This study evaluated the usefulness of PET imaging biomarkers with 64Cu-PCTA-cetuximab and 18F-FDG-PET for anti-EGFR immunotherapy in ESCC models. In vivo EGFR status and glucose metabolism by cetuximab treatment were evaluated using 64Cu-PCTA-cetuximab and 18F-FDG-PET, respectively. Therapeutic responses with imaging biomarkers were confirmed by western blot and immunohistochemistry. TE-4 and TE-8 tumors were clearly visualized by 64Cu-PCTA-cetuximab, and EGFR expression on TE-8 tumors showed 2.6-fold higher uptake than TE-4. Tumor volumes were markedly reduced by cetuximab in TE-8 tumor (92.5 ± 5.9%), but TE-4 tumors were refractory to cetuximab treatment. The SUVs in 64Cu-PCTA-cetuximab and 18F-FDG-PET images were statistically significantly reduced by cetuximab treatment in TE-8 but not in TE-4. 64Cu-PCTA-cetuximab and 18F-FDG-PET images were well correlated with EGFR and pAkt levels. 64Cu-PCTA-cetuximab immuno-PET had a potential for determining EGFR level and monitoring therapeutic response by anti-EGFR therapy. 18F-FDG-PET was also attractive for monitoring efficacy of anti-EGFR therapy. In conclusion, PET imaging biomarkers may be useful for selecting patients that express target molecules and for monitoring therapeutic efficacy of EGFR-targeted therapy in ESCC patients.

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“…In this background, the two most recent NGS-based studies from China reported the frequent presence of hotspot mutations as well as copy number aberrations in the early stages of ESCCs [3, 9]. These observations were rather astonishing, since intraepithelial neoplasias (IENs) are generally considered to be premalignant, and treatment is not actively recommended [10]. If such somatic aberrations were present, early treatment would be more reasonable.…”

Section: Introductionmentioning

confidence: 99%

“…In Japan, early esophageal lesions (intraepithelial neoplasia [IEN], invasion limited to the epithelium [EP], invasion limited to the lamina propria mucosae [LPM/M2], and invasion limited to the muscularis mucosae [MM/M3]) are increasingly considered to be appropriate targets for ESD. However, among IENs, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN) are often classified as premalignant in Western countries and their malignant potential has not yet been well characterized [10]. ESD and EMR target early neoplastic lesions and tumor tissues can be obtained en bloc ; thus, early esophageal specimens resected by ESD or EMR provide ideal materials for cancer-related gene analysis of very early esophageal neoplasia.…”

Section: Introductionmentioning

confidence: 99%

Target sequencing of cancer-related genes in early esophageal squamous neoplasia resected by endoscopic resection in Japanese patients

et al. 2018

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Background and AimsNext generation sequencing (NGS) has revealed a great deal about cancer-related somatic changes in esophageal squamous cell neoplasia; however, the changes in the very early stages remain unclear.ResultsTP53 (87%) and CDKN2A (20%) hot spot mutations were frequently found in early lesions. TP53 was the most common mutation (LGIN/HGIN, 86%; EP, 83%; LPM, 95%; MM/SM1, 80%), followed by CDKN2A (29%, 28%, 16% and 10%, respectively); the frequency of other mutations increased as the disease advanced (p < 0.01). Copy number variation analysis revealed copy number aberrations in multiple genes, including PIK3CA amplification (48%). NGS was superior to p53 immunostaining for detecting TP53 mutations (74% vs. 87%); in combination, the two tests improved detectability to 94%. Clinically, smoking was associated with the occurrence of TP53 mutations in these early lesions (p = 0.049).Materials and MethodsFifty-four early esophageal neoplasia lesions from 47 patients treated by endoscopic resection (low-grade intraepithelial neoplasia [LGIN], n = 1; high-grade intraepithelial neoplasia [HGIN] n = 7; invasion limited to epithelium [EP/M1], n = 18; lamina propria mucosae [LPM/M2], n = 19; muscularis mucosae [MM/M3], n = 8; and upper third of the SM [SM1], n = 2) were isolated from formalin-fixed paraffin-embedded tissue specimens by laser-capture microdissection. Target sequencing of 50 cancer-related genes was performed with an Ion Proton sequencer; their association with the clinical characteristics was investigated.ConclusionsMutations of TP53 and CDKN2A, and PIK3CA amplification were common in early esophageal squamous neoplasia, while other mutations accumulated with disease progression. An understanding of these molecular events might provide a molecular basis for early lesion treatment.

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Diagnosis and therapy of esophageal squamous cell dysplasia and early esophageal squamous cell cancer

Cited by 9 publications

References 73 publications

Role of endoscopic therapy in early esophageal cancer

Role of endoscopic therapy in early esophageal cancer

PET Imaging Biomarkers of Anti-EGFR Immunotherapy in Esophageal Squamous Cell Carcinoma Models

Target sequencing of cancer-related genes in early esophageal squamous neoplasia resected by endoscopic resection in Japanese patients

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