Esophageal Squamous Cell Carcinoma In Japan Research Articles

Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review.

Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.

Endoscopic Diagnosis and Treatment of Superficial Esophageal Squamous Cell Cancer: Present Status and Future Perspectives.

This review provides information regarding the preoperative examinations, indications for endoscopic resection (ER), and curability assessment in subjects with superficial esophageal squamous cell carcinoma (SCC). Narrow-band imaging (NBI) is a more sensitive modality for detecting esophageal cancer than conventional observation, and esophageal observation using NBI is thus recommended for the detection of superficial esophageal cancer. It is also important to adjust the volume of air in the esophagus during observation. Workup by non-magnifying followed by magnifying endoscopy is a common process for diagnosing the invasion depth of superficial esophageal SCCs in Japan. Endoscopic ultrasonography carries a risk of overdiagnosis, and its routine use is therefore not recommended. The Japanese endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer considered the indications for ER based on the results of studies focusing on clinical MM/SM1 cancers, and concluded that clinical MM/SM1 carcinomas, except circumferential carcinoma, were an indication for ER. The curative effect of ER should be assessed based on histologic examination of the resected specimens. ER should be conducted based on a thorough understanding of the preoperative diagnosis, indication, curability, and additional treatment of esophageal SCC.

Indications of esophageal cancer for endoscopic submucosal dissection, curability, and future perspectives

This review considers the preferred preoperative examinations, indications for endoscopic submucosal dissection (ESD), and curative ability of ESD in patients with esophageal squamous cell carcinoma (SCC). Endoscopic evaluation by non-magnifying endoscopy followed by magnifying endoscopy is a common procedure for diagnosing invasion depth of superficial esophageal SCCs in Japan. However, endoscopic ultrasonography may increase overdiagnosis of the depth of cancer invasion, and therefore should not be performed routinely. Image-enhanced magnifying endoscopy or iodine staining is recommended for diagnosing the lateral extent of esophageal SCC. The indications for ESD include clinical T1a-epithelial/lamina propria (EP/LPM) N0M0 non-circumferential lesions, clinical T1a EP/LPM N0M0 circumferential lesions ≤ 50 mm, and clinical T1a-muscularis mucosae/T1b-submucosa 1 cancer (invading submucosa by ≤ 200 µm) N0M0 non-circumferential lesions. Pathological T1a EP/LPM without vascular invasion is defined as curative resection, while pathological T1a MM without vascular invasion is considered as non-curative resection, with undetermined recommendations for additional treatment. Pathological T1b cancer invading the submucosa or pathological vascular invasion-positivity is considered as non-curative resection, and additional treatment is recommended. An accurate preoperative diagnosis, appropriate indication, and adequate curability assessment based on the pathological diagnosis of resected specimens are important for effective ESD.

Whole genome sequencing analysis identifies recurrent structural alterations in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in the Asian region, including Japan. A previous study reported mutational landscape of Japanese ESCCs by using exome sequencing. However, somatic structural alterations were yet to be explored. To provide a comprehensive mutational landscape, we performed whole genome sequencing (WGS) analysis of biopsy specimens from 20 ESCC patients in a Japanese population. WGS analysis identified non-silent coding mutations of TP53, ZNF750 and FAT1 in ESCC. We detected six mutational signatures in ESCC, one of which showed significant association with smoking status. Recurrent structural variations, many of which were chromosomal deletions, affected genes such as LRP1B, TTC28, CSMD1, PDE4D, SDK1 and WWOX in 25%–30% of tumors. Somatic copy number amplifications at 11q13.3 (CCND1), 3q26.33 (TP63/SOX2), and 8p11.23 (FGFR1) and deletions at 9p21.3 (CDKN2A) were identified. Overall, these multi-dimensional view of genomic alterations improve the understanding of the ESCC development at molecular level and provides future prognosis and therapeutic implications for ESCC in Japan.

The use of neoadjuvant therapy for resectable locally advanced thoracic esophageal squamous cell carcinoma in an analysis of 5016 patients from 305 designated cancer care hospitals in Japan.

Recent studies have shown the benefits of neoadjuvant therapy with chemotherapy or chemoradiotherapy for resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC). The aim of our study was to elucidate the use of neoadjuvant therapy for thoracic ESCC in Japan. Data on patients with stage IB-III thoracic ESCC were retrieved from the national database of hospital-based cancer registries combined with claims data between 2012 and 2013. These data were analyzed using a mixed-effect logistic regression analysis, with a focus on exploring patterns in the first-line treatment for ESCC, including proportion of patients who received neoadjuvant therapy, and investigating the hospital characteristics and patient factors associated with the use of neoadjuvant therapy. Of the 5016 patients with stage IB-III thoracic ESCC at the 305 participating hospitals, 34.2% received neoadjuvant therapy (neoadjuvant chemotherapy, 29.5%; neoadjuvant chemoradiotherapy, 4.7%). The therapy was less likely to be administered to older patients (≤64years, 48.8%; 65-70years, 42.0%; 70-75years, 33.9%; 75-80years, 22.2%; 80-85years, 3.8%; ≥85years, 1.4%) and at hospitals with a low volume of patients (very high, 42.1%; high, 37.5%; low, 30.7%; and very low, 26.4%). This trend was confirmed by regression analysis. Based on our results, in Japan, relatively few patients with resectable locally advanced thoracic ESCC receive neoadjuvant therapy, with older patients and patients at lower volume hospitals being less likely than other patients to receive the neoadjuvant therapy. We recommend that the process of treatment decision-making be assessed at both the patient and hospital levels so that patients can consider various treatment options, including neoadjuvant therapy with surgery in Japan.

Review of chemotherapeutic approaches for operable and inoperable esophageal squamous cell carcinoma.

The predominant histological types of esophageal cancer are adenocarcinoma and squamous cell carcinoma. Since these two histological types present as different diseases in terms of their epidemiology, pathologenesis, and tumor biology, separate therapeutic approaches should be developed against each type. While surgical resection remains the dominant therapeutic intervention for patients with operable esophageal squamous cell carcinoma (ESCC), their high rates of tumor recurrence have prompted investigation of multimodality therapies that combine surgery with chemotherapy, radiotherapy, and chemoradiotherapy. In Japan, preoperative chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) followed by radical esophagectomy has been accepted as the standard therapeutic approach for resactable clinical Stage II/III ESCC. Similarly, the CDDP and 5-FU regimen has been accepted as the first-line treatment for metastatic and unresectable ESCCs in Japan. Thus, in Japan chemotherapy is an indispensable component of therapy for both resectable and unresectable ESCCs. This review discusses the current knowledge, rationale, and available data regarding chemotherapy for resectable and unresectable ESCCs.

Comparison between neoadjuvant chemotherapy followed by surgery (NAC-S) and definitive chemoradiotherapy (CRT) in overall survival for patients with clinical stage II-III esophageal squamous cell carcinoma (ESCC) (JCOG1406-A).

127 Background: NAC-S is a standard treatment for patients (pts) with stage II/III (UICC-TNM 5th ed.) ESCC in Japan. CRT is also optionally performed for pts who refused or who are not tolerable to surgery. However, no randomized clinical trial has been conducted comparing NAC-S with CRT. The aim of this study is to explore subgroups in which survival outcome of pts undergoing CRT was potentially equivalent to NAC-S. Methods: The data of two trials for cStage II/III ESCC, JCOG9907 (accrual period: 2000-2006) and JCOG9906 (2000-2002) were used. J9907 demonstrated that NAC-S (2 course of cisplatin and 5-fluorouracil [CF] followed by surgery) showed superior OS compared with surgery followed by postoperative chemotherapy. J9906 was a single arm trial which explored the efficacy and safety of CRT (CF plus 60 Gy). Both two trials were conducted under similar eligible criteria. Subgroup analyses between two trials (serum Albmin (Alb), cT, cN, c-stage, and tumor location) using Cox proportional hazard model were performed for pts assigned to receive NAC-S in J9907 and pts in J9906. Results: All eligible pts for NAC-S group (n=164) in J9907 and all eligible pts in J9906 (CRT group: n=73) were analyzed. Pts backgrounds were similar between two groups. OS for NAC-S group was better than that for CRT group (adjusted HR 1.73; 95% CI 1.19-2.51). Subgroup analysis using Cox proportional hazard model demonstrated that all subgroups in NAC-S group showed shorter OS compared with those in CRT group (see Table). Conclusions: OS of NAC-S was favored over that of CRT. The subgroup in which OS of CRT was equivalent to that of NAC-S was not detected. For further improvement of CRT for this population, single arm trial (JCOG0909) is ongoing to evaluate the efficacy and safety of CRT modifying chemotherapy regimen and total radiation dose. [Table: see text]

High-risk human papillomavirus infection and overexpression of p53 protein in squamous cell carcinoma of the esophagus from Japan.

The present study was undertaken in order to investigate the possible involvement of high-risk human papillomavirus (HPV; types 16 and 18) or the overexpression of p53 protein in 123 Japanese patients with esophageal squamous cell carcinoma (SCC) from five different institutions. We detected HPV DNA in 30.1% (37/123) by in situ hybridization (ISH). Of these 123 cases, HPV type 16 was detected in 22 cases and HPV type 18 in 23 cases. In addition, HPV types 16 and 18 were detected simultaneously in eight cases. We found an almost similar incidence of HPV infection at five different places in Japan. Then, among these patients, 24 fresh tumor samples were also examined for screening the presence of HPV DNA using dot blot hybridization (DBH) and polymerase chain reaction (PCR). We detected HPV DNA in 20.8% (5/24) by DBH and in 12.5% (3/24) by PCR. P53 protein overexpression was found in 34.1% (43/123) by immunohistochemistry (IHC). Furthermore, in 43 cases from Kochi Medical School, the group positive for p53 antibody statistically showed worse survival rate than the group negative for both HPV DNA and p53 antibody. Judging from these results obtained in the present study, HPV infection and p53 overexpression are frequently detected and involved in the carcinogenesis of esophageal SCC in Japan. We also found that no significant geographical difference of both HPV infection and p53 overexpression of esophageal SCC was seemingly present in Japan.