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Zeng M, Lin A, Jiang A, Qiu Z, Zhang H, Chen S, Xu M, Liu Z, Cheng Q, Zhang J, Luo P. Decoding the mechanisms behind second primary cancers. J Transl Med 2025; 23:115. [PMID: 39856672 PMCID: PMC11762917 DOI: 10.1186/s12967-025-06151-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 01/19/2025] [Indexed: 01/27/2025] Open
Abstract
Second Primary Cancers (SPCs) are defined as cancers that develop either simultaneously or metachronously in the same individual who has been diagnosed with and survived one primary cancer. SPCs exhibit a high incidence rate and represent the primary cause of mortality among survivors of first primary cancers. There is growing concern about the dangers of SPCs. This review summarizes recent studies on the mechanisms of SPCs, including the roles of genomic changes after first primary cancer (FPC) treatments, stromal cell phenotypic and metabolic changes, hormone levels and receptor expression, immunosuppression, aberrant gene methylation, EGFR signaling, and cell-free DNA in SPC development. This comprehensive analysis contributes to elucidating current research trends in SPC mechanisms and enhances our understanding of the underlying pathophysiology. Furthermore, potential applications of intratumoral microbes, single-cell multi-omics, and metabolomics in investigating SPC mechanisms are also discussed, providing new ideas for follow-up studies.
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Affiliation(s)
- Meiyuan Zeng
- Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China
| | - Anqi Lin
- Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China
| | - Aimin Jiang
- Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Zhengang Qiu
- Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Hongman Zhang
- Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China
| | - Shifu Chen
- HaploX Biotechnology, Shenzhen, China
- Faculty of Data Science, City University of Macau, Macau, China
| | | | - Zaoqu Liu
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Quan Cheng
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, China.
| | - Jian Zhang
- Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China.
| | - Peng Luo
- Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China.
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Wang WL, Tsai YN, Hsu MH, Lin JT, Wang HP, Lee CT. Endoscopic background mucosal resurfacing to prevent metachronous recurrence of superficial esophageal squamous cell cancer after curative endoscopic submucosal dissection: randomized pilot study with 5-year follow-up (with video). Gastrointest Endosc 2024:S0016-5107(24)03684-8. [PMID: 39521094 DOI: 10.1016/j.gie.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 08/10/2024] [Accepted: 11/03/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND AIMS Metachronous recurrence frequently develops in patients with superficial esophageal squamous cell carcinomas (ESCCs) after curative endoscopic submucosal dissection (ESD), especially in those with multiple (>10) small Lugol-voiding lesions (LVLs) over the endoscopic background mucosa (ie, speckled pattern). We conducted a randomized controlled trial to investigate whether endoscopic radiofrequency ablation (RFA) for endoscopic background mucosal resurfacing (EBMR) can decrease the rate of metachronous neoplasia. METHODS Patients who received curative ESD and whose Lugol staining showed a speckled pattern over the background mucosa were randomly assigned in a 1:1 ratio to receive either RFA (EBMR group) or endoscopic surveillance alone (control group). EBMR with RFA was performed with a balloon device for circumferential ablation of the total esophageal mucosa 2 to 3 months after ESD. The primary outcome was the metachronous recurrence of squamous neoplasia during a 5-year follow-up period. Secondary outcomes were major adverse events. RESULTS Of 112 patients screened, 30 were randomized to receive EBMR (n = 15) or surveillance (n = 15). The mean procedure time of EBMR was 30.7 minutes (range, 25-40). One patient developed post-RFA stenosis, which resolved after 3 sessions of endoscopic dilation. EBMR reduced the risk of metachronous recurrence (0% in the EBMR group vs 53% in the control group, P = .001), with a number needed to treat of 1.9. Reversal of the Lugol-staining speckled pattern to only a few LVLs occurred in all patients and persisted for at least 5 years in the ablation group. CONCLUSIONS In this randomized trial of patients with multiple small LVLs over the endoscopic background after curative ESD, EBMR with balloon-type RFA is a promising and safe procedure for preventing metachronous recurrence over 5 years of follow-up. (Clinical trial registration number: NCT03183115.).
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Affiliation(s)
- Wen-Lun Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ying-Nan Tsai
- Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Ming-Hung Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Jaw-Town Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Hsiu-Po Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ching-Tai Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
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Nobre R, Uedo N, Ishihara R, Maluf-Filho F. Beyond borders: When will Western countries follow Japanese progress in endoscopic diagnosis and treatment of superficial pharyngeal cancer? Gastrointest Endosc 2024; 100:756-758. [PMID: 39340516 DOI: 10.1016/j.gie.2024.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 05/06/2024] [Accepted: 05/22/2024] [Indexed: 09/30/2024]
Affiliation(s)
- Renata Nobre
- Department of Gastroenterology, Sao Paulo Cancer Institute, Sao Paulo, Brazil
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Fauze Maluf-Filho
- Department of Gastroenterology, Sao Paulo Cancer Institute, Sao Paulo, Brazil
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Hori K, Katada C, Okada H, Katagiri A, Matsuo Y, Yokoyama T, Yano T, Suzuki H, Shimizu Y, Furue Y, Nakanishi H, Koike T, Takizawa K, Hirao M, Yoshii T, Yamanouchi T, Kawakubo H, Kobayashi N, Shimoda T, Ochiai A, Ishikawa H, Yokoyama A, Muto M. 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. Esophagus 2024; 21:31-40. [PMID: 38070099 DOI: 10.1007/s10388-023-01033-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 11/03/2023] [Indexed: 01/25/2024]
Abstract
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.
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Affiliation(s)
- Keisuke Hori
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
- Department of Internal Medicine, Tsuyama Chuo Hospital, Tsuyama, Japan
| | - Chikatoshi Katada
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho Syhogoin Sakyo, Kyoto, 606-8507, Japan.
- Department of Real World Data Research and Development, Graduate School of Medicine, Kyoto University, 54 Kawaharacho Syhogoin Sakyo, Kyoto, 606-8507, Japan.
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Atsushi Katagiri
- Department of Medicine, Division of Gastroenterology, Showa University Hospital, Tokyo, Japan
| | - Yasumasa Matsuo
- Department of Gastroenterology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tetsuji Yokoyama
- Department of Health and Promotion, National Institute of Public Health, Wako, Japan
| | - Tomonori Yano
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan
| | - Haruhisa Suzuki
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yuichi Shimizu
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Yasuaki Furue
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hiroyoshi Nakanishi
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
- Department of Endoscopy, Koyukai Shin-Sapporo Hospital, Hokkaido, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Takako Yoshii
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Takenori Yamanouchi
- Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan
| | - Nozomu Kobayashi
- Department of Gastroenterology, Tochigi Cancer Center, Utsunomiya, Japan
| | - Tadakazu Shimoda
- Division of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Atsushi Ochiai
- Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Yokoyama
- Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho Syhogoin Sakyo, Kyoto, 606-8507, Japan
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Huang CC, Ying LQ, Chen YP, Ji M, Zhang L, Liu L. Metachronous primary esophageal squamous cell carcinoma and duodenal adenocarcinoma: A case report and review of literature. World J Gastrointest Surg 2023; 15:2627-2638. [PMID: 38111767 PMCID: PMC10725532 DOI: 10.4240/wjgs.v15.i11.2627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 09/23/2023] [Accepted: 10/26/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND The prevalence of multiple primary malignant neoplasms (MPMNs) is increasing in parallel with the incidence of malignancies, the continual improvement of diagnostic models, and the extended life of patients with tumors, especially those of the digestive system. However, the co-existence of MPMNs and duodenal adenocarcinoma (DA) is rarely reported. In addition, there is a lack of comprehensive analysis of MPMNs regarding multi-omics and the tumor microenvironment (TME). CASE SUMMARY In this article, we report the case of a 56-year-old man who presented with a complaint of chest discomfort and abdominal distension. The patient was diagnosed with metachronous esophageal squamous cell carcinoma and DA in the Department of Oncology. He underwent radical resection and chemotherapy for the esophageal tumor, as well as chemotherapy combined with a programmed death-1 inhibitor for the duodenal tumor. The overall survival was 16.6 mo. Extensive evaluation of the multi-omics and microenvironment features of primary and metastatic tumors was conducted to: (1) Identify the reasons responsible for the poor prognosis and treatment resistance in this case; and (2) Offer novel diagnostic and therapeutic approaches for MPMNs. This case demonstrated that the development of a second malignancy may be independent of the location of the first tumor. Thus, tumor recurrence (including metastases) should be distinguished from the second primary for an accurate diagnosis of MPMNs. CONCLUSION Multi-omics characteristics and the TME may facilitate treatment selection, improve efficacy, and assist in the prediction of prognosis.
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Affiliation(s)
- Chun-Chun Huang
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Le-Qian Ying
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Yan-Ping Chen
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Min Ji
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Lu Zhang
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
| | - Lin Liu
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu Province, 210009, China
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Sohda M, Yokobori T, Kimura A, Kosaka T, Yoshida K, Hakamada K, Natsugoe S, Taketomi A, Saeki H, Shirabe K, Kuwano H. Efficacy of chemotherapy for comorbid cancer in patients with simultaneous double cancers: a multicenter study. Surg Today 2023; 53:98-108. [PMID: 35913634 DOI: 10.1007/s00595-022-02542-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 05/01/2022] [Indexed: 01/11/2023]
Abstract
PURPOSE Anticancer drugs for double cancers are selected based on their therapeutic effects on the target cancer, but there are insufficient data on the effects of anticancer drugs on comorbid cancer. We investigated the effect of chemotherapy on comorbid cancer in patients with simultaneous double cancers. METHODS The subjects of this retrospective study were 51 patients with simultaneous double cancers at the time of receiving systemic chemotherapy. We evaluated the types of anticancer drugs used for double cancers, the therapeutic effects on targeted and comorbid cancers, and prognoses. RESULTS Disease control was achieved for 90.9% of the target cancers and 90.7% of the comorbid cancers. The prognosis was significantly better when the disease was controlled, not only in the target cancer but also in the comorbid cancer. CONCLUSION Physicians treating double cancers should develop treatment strategies focusing not only on the treatment for advanced cancer, but also on the course of comorbidities and the therapeutic effects of anticancer drugs. This study is important because it presents new possibilities to expand the indications for anticancer drugs, while allowing unnecessary clinical research to be avoided.
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Affiliation(s)
- Makoto Sohda
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
| | - Takehiko Yokobori
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Akiharu Kimura
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Takayuki Kosaka
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Kazuhiro Yoshida
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Kenichi Hakamada
- Department of Gastrointestinal Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.,Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ken Shirabe
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.,Fukuoka City Hospital, Fukuoka, Japan
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Overall Survival for Esophageal Squamous Cell Carcinoma with Multiple Primary Cancers after Curative Esophagectomy-A Retrospective Single-Institution Study. Cancers (Basel) 2022; 14:cancers14215263. [PMID: 36358682 PMCID: PMC9658684 DOI: 10.3390/cancers14215263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/03/2022] [Accepted: 10/25/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Advances in surgical techniques and treatment modalities have improved the outcomes of esophageal cancer, yet difficult decision making for physicians while encountering multiple primary cancers (MPCs) continues to exist. The aim of this study was to evaluate long-term survival for esophageal squamous cell carcinoma (SCC) associated with MPCs. Methods: Data from 544 patients with esophageal SCC who underwent surgery between 2005 and 2017 were reviewed to identify the presence of simultaneous or metachronous primary cancers. The prognostic factors for overall survival (OS) were analyzed. Results: Three hundred and ninety-seven patients after curative esophagectomy were included, with a median observation time of 44.2 months (range 2.6−178.6 months). Out of 52 patients (13.1%) with antecedent/synchronous cancers and 296 patients without MPCs (control group), 49 patients (12.3%) developed subsequent cancers after surgery. The most common site of other primary cancers was the head and neck (69/101; 68.3%), which showed no inferiority in OS. Sex and advanced clinical stage (III/IV) were independent risk factors (p = 0.031 and p < 0.001, respectively). Conclusion: Once curative esophagectomy can be achieved, surgery should be selected as a potential therapeutic approach if indicated, even with antecedent/synchronous MPCs. Subsequent primary cancers were often observed in esophageal SCC, and optimal surveillance planning was recommended.
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Wan L, Yin FY, Tan HH, Meng L, Hu JH, Xiao BR, Zhu ZF, Liu N, Qi HP. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male. Open Life Sci 2022; 17:1223-1228. [PMID: 36185408 PMCID: PMC9483829 DOI: 10.1515/biol-2022-0465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 06/18/2022] [Accepted: 06/20/2022] [Indexed: 11/23/2022] Open
Abstract
Multiple primary malignant neoplasms (MPMNs) are defined as multiple tumors with different pathogenic origins. MPMNs are rare, but the morbidity rate is on the rise. With the development of anti-tumor treatments, such as targeted therapy and immunotherapy, the overall survival of cancer patients has been significantly prolonged, leading to an increased number of patients with MPMNs. A crucial aspect of MPMNs management is deciding how to schedule further treatments according to individual tumor risk. This process involves a multidisciplinary physician team to ensure favorable outcomes. Herein we report a 60-year-old male who developed four different malignancies, including esophageal squamous cell carcinoma, upper urinary tract urothelial carcinoma, mediastinal small cell lung cancer, and left lung squamous cell carcinoma over 20 years and received appropriate treatment of each cancer with long survival.
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Affiliation(s)
- Long Wan
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
| | - Feng-Yan Yin
- Department of Thyroid Surgery, Tai'an Central Hospital, Tai'an 271000, Shandong Province, China
| | - Hai-Hua Tan
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
| | - Li Meng
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
| | - Jian-Hua Hu
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
| | - Bao-Rong Xiao
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
| | - Zhao-Feng Zhu
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
| | - Ning Liu
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
| | - Huan-Peng Qi
- Department of Oncological Radiotherapy, Tai'an Central Hospital, No. 29 Longtan Road, Tai'an 271000, Shandong Province, China
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Effect of chemoradiation on the development of second primary cancers after endoscopic resection of T1 esophageal squamous cell carcinoma. Esophagus 2022; 19:469-476. [PMID: 35320430 DOI: 10.1007/s10388-022-00917-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Accepted: 03/10/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Patients with early esophageal squamous cell carcinoma (ESCC) may develop multiple second primary ESCC and cancers in other organs even after curative endoscopic resection (ER). We investigated whether administration of chemoradiotherapy (CRT) after ER decreases the incidence of second primary cancers. METHODS We conducted a post hoc analysis of the prospective study. Among the registered 170 patients with clinical submucosal ESCC, 74 underwent ER alone, and 96 underwent ER followed by CRT (ER + CRT) because of pathological results of submucosal or lympho-vascular invasion. We compared the incidence of second primary cancers in esophagus and in other organs between two treatment groups. A univariate analysis was performed to investigate the related risk factors. All patients were followed up with esophagogastroduodenoscopy and CT every 4 months for the first 3 years and every 6 months thereafter. RESULTS Sixty-one ESCC were detected in 32 patients, and the 3-year cumulative incidence of multiple ESCCs was not different between ER + CRT and ER alone (10.4% vs. 13.5%). Sixty-three second primary cancers in other organs were detected in 45 patients, and there was no difference in the cumulative incidence between two groups. The risk factors for multiple ESCCs were high alcohol consumption and grade C multiple Lugol-voiding lesions. Heavy drinker or patients with grade C multiple Lugol-voiding lesion rather than CRT were at risk for second primary ESCC. CONCLUSION CRT after ER did not decrease the cumulative incidence of second primary ESCC nor cancers in other organs comparing with ER alone.
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10
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Can gene therapy be used to prevent cancer? Gene therapy for aldehyde dehydrogenase 2 deficiency. Cancer Gene Ther 2022; 29:889-896. [PMID: 34799722 PMCID: PMC9117562 DOI: 10.1038/s41417-021-00399-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/24/2021] [Accepted: 10/08/2021] [Indexed: 11/08/2022]
Abstract
Approximately 8% of the world population and 35-45% of East Asians are carriers of the hereditary disorder aldehyde dehydrogenase 2 (ALDH2) deficiency. ALDH2 plays a central role in the liver to metabolize ethanol. With the common E487K variant, there is a deficiency of ALDH2 function; when ethanol is consumed, there is a systemic accumulation of acetaldehyde, an intermediate product in ethanol metabolism. In ALDH2-deficient individuals, ethanol consumption acutely causes the "Alcohol Flushing Syndrome" with facial flushing, tachycardia, nausea, and headaches. With chronic alcohol consumption, ALDH2 deficiency is associated with a variety of disorders, including a remarkably high risk for aerodigestive tract cancers. Acetaldehyde is a known carcinogen. The epidemiologic data relating to the association of ALDH2 deficiency and cancer risk are striking: ALDH2 homozygotes who are moderate-to-heavy consumers of ethanol have a 7-12-fold increased risk for esophageal cancer, making ALDH2 deficiency the most common hereditary disorder associated with an increased cancer risk. In this review, we summarize the genetics and biochemistry of ALDH2, the epidemiology of cancer risk associated with ALDH2 deficiency, the metabolic consequences of ethanol consumption associated with ALDH2 deficiency, and gene therapy strategies to correct ALDH2 deficiency and its associated cancer risk. With the goal of reducing the risk of aerodigestive tract cancers, in the context that ALDH2 is a hereditary disorder and ALDH2 functions primarily in the liver, ALDH2 deficiency is an ideal target for the application of adeno-associated virus-mediated liver-directed gene therapy to prevent cancer.
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Muto M, Katada C, Yokoyama T, Yano T, Oda I, Ezoe Y, Tanabe S, Shimizu Y, Doyama H, Koike T, Takizawa K, Hirao M, Okada H, Ogata T, Katagiri A, Yamanouchi T, Matsuo Y, Kawakubo H, Omori T, Kobayashi N, Shimoda T, Ochiai A, Ishikawa H, Baba K, Amanuna Y, Yokoyama A, Ohashi S, Yokoyama A. Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study. GASTRO HEP ADVANCES 2022; 1:265-276. [PMID: 39131127 PMCID: PMC11308419 DOI: 10.1016/j.gastha.2021.10.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 10/07/2021] [Indexed: 08/13/2024]
Abstract
Background and Aims Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients' quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. Methods This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1-9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. Results LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0-57.2 and 13.3%, 95% CI = 8.1-21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26-0.85 and 0.49, 95% CI = 0.26-0.91, respectively). Conclusion Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.
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Affiliation(s)
- Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Tetsuji Yokoyama
- Department of Health Promotion, National Institute of Public Health, Wako, Japan
| | - Tomonori Yano
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yasumasa Ezoe
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Satoshi Tanabe
- Research and Development Center for New Frontiers, Kitasato University School of Medicine, Sagamihara, Japan
| | - Yuichi Shimizu
- Division of Endoscopy, Hokkaido University Hospital, Sapporo, Japan
| | - Hisashi Doyama
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Takashi Ogata
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Atsushi Katagiri
- Division of Gastroenterology, Department of Medicine, Showa University Hospital, Tokyo, Japan
| | - Takenori Yamanouchi
- Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Japan
| | - Yasumasa Matsuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan
| | - Tai Omori
- Department of Surgery, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan
| | - Nozomu Kobayashi
- Department of Gastroenterology, Tochigi Cancer Center, Utsunomiya, Japan
| | - Tadakazu Shimoda
- Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Atsushi Ochiai
- Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kiichiro Baba
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yusuke Amanuna
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Akira Yokoyama
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shinya Ohashi
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Akira Yokoyama
- Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Japan
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12
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Effects of steroid use for stenosis prevention after endoscopic submucosal dissection for cervical esophageal cancer. Int J Clin Oncol 2022; 27:940-947. [PMID: 35194703 DOI: 10.1007/s10147-022-02139-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 02/09/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND AND AIM Esophageal stenosis is a serious complication after endoscopic submucosal dissection (ESD) for thoracic esophageal cancer (TEC), and steroid has been applied for stenosis prevention. However, the rate of stenosis and effect of steroid for ESD of cervical esophageal cancer (CEC) remain unknown. The aim was to clarify the rate and managements of post-ESD stenosis for CEC. METHODS A total of 325 lesions with 272 patients who underwent ESD for esophageal cancers were enrolled and were divided to the CEC group (43 lesions) or the TEC group (282 lesions). Patient characteristics, clinicopathological features, procedure-related outcomes of esophageal ESD, stenosis rate and clinical outcome of steroid use cases were evaluated. RESULTS More patients in the CEC group received preventive steroid treatment compared to the TEC group (37.2% vs 14.5%, P = 0.001). The rate of post-ESD stenosis tended to be higher in the CEC group (11.6%) than in the TEC group (6.7%). For cases of 3/4 ≤ of circumference, local injection with oral steroid had lower stenosis rate than local injection only in both groups (CEC 40% vs 100%, TEC 30.7% vs 56.3%). More sessions and longer duration of dilation were needed to release the stenosis in the CEC group (20 times vs. 5 times, P = 0.015; 196 days vs. 55 days, P = 0.043). CONCLUSION The post-ESD stenosis rate of CEC tended to be higher than that of TEC. More intensive preventive measures for post-ESD stenosis may be needed for CEC than TEC.
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13
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Mitani S, Kato K, Daiko H, Ito Y, Nozaki I, Kojima T, Yano M, Nakagawa S, Ueno M, Watanabe M, Tsunoda S, Abe T, Kadowaki S, Kadota T, Sasaki K, Machida R, Kitagawa Y. Second primary malignancies in patients with clinical T1bN0 esophageal squamous cell carcinoma after definitive therapies: supplementary analysis of the JCOG trial: JCOG0502. J Gastroenterol 2022; 57:455-463. [PMID: 35546373 PMCID: PMC9232445 DOI: 10.1007/s00535-022-01870-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 02/26/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Previous studies have suggested that patients with esophageal squamous cell carcinoma (ESCC) are still at a high risk of developing second primary malignancies (SPMs) after definitive therapies. We evaluated the development of SPMs and explored its risk factors in patients with clinical T1bN0 ESCC. METHODS JCOG0502 prospectively compared esophagectomy with definitive chemo-radiotherapy for clinical T1bN0 ESCC. Here, we reviewed all JCOG0502 patients' data for SPMs and investigated the risk factors for SPMs using uni-variable and multivariable analyses by Fine and Gray model. RESULTS Among 379 enrolled patients, 213 underwent esophagectomy and 166 received chemo-radiotherapy. Patient characteristics were male (85%); median age [63 (range 41-75) years; location of the primary tumor (upper/middle/lower thoracic esophagus, 11%/63%/27%, respectively]; alcohol consumption history (79%); smoking history (66%); prevalence of no/several/many/unknown Lugol-voiding lesions (LVLs) (45%/36%/8%/11%, respectively). In a median follow-up of 7.1 years, 118 SPMs occurred in 99 (26%) patients. Cumulative incidences of SPMs after 3, 5, and 10 years were 9%, 15%, and 36%, respectively. The most common primary tumor sites were the head and neck (35%), stomach (20%) and lungs (14%). In multivariable analyses, compared to no LVLs, several LVLs [hazard ratio (HR) 2.24, 95% confidential interval (CI) 1.32-3.81] and many LVLs (HR 2.88, 95% CI 1.27-6.52) were significantly associated with the development of SPMs. Sixteen patients died due to the SPMs. CONCLUSION The incidence of SPMs was high. The presence of LVLs, which was a predictive factor for SPMs, may be useful for surveillance planning.
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Affiliation(s)
- Seiichiro Mitani
- Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.
- Department of Medical Oncology, Faculty of Medicine Kindai University, 377-2 Onohigashi, Osaka-sayama, Osaka, 589-8511, Japan.
| | - Ken Kato
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroyuki Daiko
- Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan
| | - Isao Nozaki
- Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
| | - Takashi Kojima
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Masahiko Yano
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Satoru Nakagawa
- Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Masaki Ueno
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Masaya Watanabe
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Shigeru Tsunoda
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tetsuya Abe
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Aichi, Japan
| | - Shigenori Kadowaki
- Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan
| | - Tomohiro Kadota
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan
| | - Keita Sasaki
- Japan Clinical Oncology Group Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Ryunosuke Machida
- Japan Clinical Oncology Group Data Center, National Cancer Center Hospital, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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14
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Ikenoyama Y, Yoshio T, Tokura J, Naito S, Namikawa K, Tokai Y, Yoshimizu S, Horiuchi Y, Ishiyama A, Hirasawa T, Tsuchida T, Katayama N, Tada T, Fujisaki J. Artificial intelligence diagnostic system predicts multiple Lugol-voiding lesions in the esophagus and patients at high risk for esophageal squamous cell carcinoma. Endoscopy 2021; 53:1105-1113. [PMID: 33540446 DOI: 10.1055/a-1334-4053] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND It is known that an esophagus with multiple Lugol-voiding lesions (LVLs) after iodine staining is high risk for esophageal cancer; however, it is preferable to identify high-risk cases without staining because iodine causes discomfort and prolongs examination times. This study assessed the capability of an artificial intelligence (AI) system to predict multiple LVLs from images that had not been stained with iodine as well as patients at high risk for esophageal cancer. METHODS We constructed the AI system by preparing a training set of 6634 images from white-light and narrow-band imaging in 595 patients before they underwent endoscopic examination with iodine staining. Diagnostic performance was evaluated on an independent validation dataset (667 images from 72 patients) and compared with that of 10 experienced endoscopists. RESULTS The sensitivity, specificity, and accuracy of the AI system to predict multiple LVLs were 84.4 %, 70.0 %, and 76.4 %, respectively, compared with 46.9 %, 77.5 %, and 63.9 %, respectively, for the endoscopists. The AI system had significantly higher sensitivity than 9/10 experienced endoscopists. We also identified six endoscopic findings that were significantly more frequent in patients with multiple LVLs; however, the AI system had greater sensitivity than these findings for the prediction of multiple LVLs. Moreover, patients with AI-predicted multiple LVLs had significantly more cancers in the esophagus and head and neck than patients without predicted multiple LVLs. CONCLUSION The AI system could predict multiple LVLs with high sensitivity from images without iodine staining. The system could enable endoscopists to apply iodine staining more judiciously.
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Affiliation(s)
- Yohei Ikenoyama
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan
| | - Toshiyuki Yoshio
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Tada Tomohiro Institute of Gastroenterology and Proctology, Saitama, Japan
| | - Junki Tokura
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Sakiko Naito
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Ken Namikawa
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshitaka Tokai
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shoichi Yoshimizu
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yusuke Horiuchi
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akiyoshi Ishiyama
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiaki Hirasawa
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Tada Tomohiro Institute of Gastroenterology and Proctology, Saitama, Japan
| | - Tomohiro Tsuchida
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoyuki Katayama
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan
| | - Tomohiro Tada
- Tada Tomohiro Institute of Gastroenterology and Proctology, Saitama, Japan.,AI Medical Service Inc., Tokyo, Japan.,Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junko Fujisaki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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15
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Chen JY, Zhang SS, Fu XY, Wen J, Yang H, Zhang YJ, Fu JH, Liu QW. The characteristics and prognostic significance of esophageal squamous cell carcinoma with synchronous multiple lesions: over 10-year experience. Esophagus 2021; 18:851-860. [PMID: 34110538 DOI: 10.1007/s10388-021-00856-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 06/01/2021] [Indexed: 02/03/2023]
Abstract
PURPOSE Esophageal squamous cell carcinoma (ESCC) is occasionally observed with synchronous multiple tumor lesions. Our study is aiming to define the clinical and prognostic features of this pathological subtype. METHODS This study included a large cohort of 1126 ESCC patients received esophagectomy with systemic lymph-node dissection between 2003 and 2013 in Sun Yat-sen University Cancer Center. The characteristics and prognostic significance of ESCC with multiple lesions were analyzed. The propensity score matching was performed to balance the baseline clinical characteristics. RESULTS A total of 103 patients (9.1%) with 216 synchronous multiple lesions were identified from postoperative gross samples. Among them, 94 patients had two lesions, and 8 patients had three lesions, while only one patient had four lesions. The consistency of pT stages and histological grade among tumor lesions from the same gross sample were 19.4% (20/103) and 37.9% (39/103), respectively. Additionally, the tumor sites, sizes, and even the pathological subtypes can be variant in one patient. The preoperative upper gastrointestinal endoscopy could only identified 80.1% of the multiple tumor lesions. The male gender (P = 0.012), positive personal cancer history (P < 0.001), and higher pN stages (P < 0.001) were independent risk factors for synchronous multiple lesions. Patients with multiple lesions showed significantly lower survival rate (P = 0.002), and the multiple-lesion was an independently adverse prognostic factor in operable ESCC (P = 0.002). CONCLUSION ESCC with multiple lesions had unique clinical features and should not be simply treated as the one-lesion ESCC. Due to its worse prognostic impact, advanced multidisciplinary therapies should be considered for patients with multiple esophageal tumor lesions.
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Affiliation(s)
- Jun-Ying Chen
- Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Guangdong Esophageal Cancer Institute, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Shui-Shen Zhang
- Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xia-Yu Fu
- Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jing Wen
- Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Guangdong Esophageal Cancer Institute, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Hong Yang
- Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Guangdong Esophageal Cancer Institute, Guangzhou, China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yi-Jun Zhang
- Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jian-Hua Fu
- Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China. .,Guangdong Esophageal Cancer Institute, Guangzhou, China. .,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
| | - Qian-Wen Liu
- Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China. .,Guangdong Esophageal Cancer Institute, Guangzhou, China. .,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
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16
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Potential roles of gastroesophageal reflux in patients with superficial esophageal squamous cell carcinoma without major causative risk factors. J Gastroenterol 2021; 56:891-902. [PMID: 34426869 DOI: 10.1007/s00535-021-01815-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 07/17/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. METHODS We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups-the very low-risk (VLR)-group and risk (R)-group-based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. RESULTS The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features-frequently observed in the posterior wall of the middle thoracic esophagus-with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. CONCLUSIONS Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.
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17
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Metachronous carcinogenesis of superficial esophagus squamous cell carcinoma after endoscopic submucosal dissection: incidence and risk stratification during long-term observation. Esophagus 2021; 18:806-816. [PMID: 33974189 DOI: 10.1007/s10388-021-00848-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 04/21/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND This study aimed to reveal long-term outcomes, such as incidence of metachronous esophageal and head and neck squamous cell carcinomas and overall survival rate, through long-term observation of patients with esophageal carcinoma post-endoscopic submucosal dissection. METHODS Risk of metachronous carcinogenesis was evaluated in 88 patients with intramucosal esophageal carcinoma (without history of metachronous esophageal or head and neck squamous cell carcinomas) who underwent endoscopic submucosal dissection from 2007 to 2008 and were endoscopically observed for > 3 years. Histologically, the papillary vessel is defined as the clock gear-like structure composed of capillaries directly penetrating the epithelium (starting from the lamina propria) and covering at least two-thirds of it, around which the tumor cells are arranged in a spiral pattern. RESULTS Median endoscopic follow-up period was 11.0 years. Cumulative 2-, 5-, and 10-year metachronous esophageal carcinoma rates were 11.4%, 20.6%, and 39.3%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple Lugol-voiding lesions (LVLs) as the single significant independent predictor. Cumulative 2-, 5-, and 10-year metachronous head and neck squamous cell carcinoma rates were 6.9%, 10.4%, and 19.6%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple LVLs, Brinkman index, papillary vessel, and younger age as significant predictive factors. Overall post-endoscopic submucosal dissection survival rates were 98.8% and 87.5% at 5 and 10 years, respectively. CONCLUSION Patients with a history of esophageal carcinoma remain at risk for metachronous carcinogenesis even > 5 years after endoscopic submucosal dissection. Thus, long-term follow-up is important.
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Hsu MH, Wang WL, Chen TH, Tai CM, Wang HP, Lee CT. Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in Taiwan. BMC Gastroenterol 2021; 21:308. [PMID: 34344303 PMCID: PMC8330105 DOI: 10.1186/s12876-021-01888-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 07/27/2021] [Indexed: 02/08/2023] Open
Abstract
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.
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Affiliation(s)
- Ming-Hung Hsu
- Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan
| | - Wen-Lun Wang
- Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan. .,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
| | - Tzu-Haw Chen
- Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ching-Tai Lee
- Department of Internal Medicine, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan.
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The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment. Acta Pharm Sin B 2021; 11:1400-1411. [PMID: 34221859 PMCID: PMC8245805 DOI: 10.1016/j.apsb.2021.02.008] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 11/29/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022] Open
Abstract
A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.
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Key Words
- 4-HNE, 4-hydroxy-2-nonenal
- ALD, alcoholic liver disease
- ALDH2
- ALDH2, aldehyde dehydrogenase 2
- AMPK, AMP-activated protein kinase
- Acetaldehyde
- BCa, bladder cancer
- COUP-TF, chicken ovalbumin upstream promoter-transcription factor
- CRC, colorectal cancer
- CSCs, cancer stem cells
- Cancer
- Cancer therapy
- DFS, disease-free survival
- EC, esophageal cancer
- FA, Fanconi anemia
- FANCD2, Fanconi anemia protein
- GCA, gastric cancer
- HCC, hepatocellular carcinoma
- HDACs, histone deacetylases
- HNC, head and neck cancer
- HNF-4, hepatocyte nuclear factor 4
- HR, homologous recombination
- LCSCs, liver cancer stem cells
- MDA, malondialdehyde
- MDR, multi-drug resistance
- MN, micronuclei
- Metastasis
- NAD, nicotinamide adenine dinucleotide
- NCEs, normochromic erythrocytes
- NER, nucleotide excision repair pathway
- NF-κB, nuclear factor-κB
- NHEJ, non-homologous end-joining
- NRF2, nuclear factor erythroid 2 (NF-E2)-related factor 2
- NRRE, nuclear receptor response element
- NSCLC, non-small-cell lung
- NeG, 1,N2-etheno-dGuo
- OPC, oropharyngeal cancer
- OS, overall survival
- OvCa, ovarian cancer
- PBMC, peripheral blood mononuclear cell
- PC, pancreatic cancer
- PdG, N2-propano-2′-deoxyguanosine
- Polymorphism
- Progression
- REV1, Y-family DNA polymerase
- SCC, squamous cell carcinoma
- TGF-β, transforming growth factor β
- Tumorigenesis
- VHL, von Hippel-Lindau
- ccRCC, clear-cell renal cell carcinomas
- εPKC, epsilon protein kinase C
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20
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Ohno K, Kawada K, Sugimoto T, Kiyokawa Y, Kawabe H, Takahashi R, Koide N, Tateishi Y, Tasaki A, Ariizumi Y, Asakage T. Evaluation of synchronous multiple primary superficial laryngo-pharyngeal cancers that were treated by endoscopic laryngo-pharyngeal surgery. Auris Nasus Larynx 2021; 48:1162-1166. [PMID: 33892989 DOI: 10.1016/j.anl.2021.03.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 02/28/2021] [Accepted: 03/25/2021] [Indexed: 11/27/2022]
Abstract
OBJECTIVE ndoscopic laryngopharyngeal surgery (ELPS) is a useful surgery for superficial cancers of the head and neck region, but it has not yet been well evaluated for synchronous multiple primary cancers (multiple primaries). The purpose of this study was to clarify the safety and usefulness of ELPS for patients with multiple superficial primary cancers in the head and neck region. METHODS rom December 2009 to December 2016, 145patients with superficial head and neck cancers underwent ELPS. The patients were divided into two groups; a group consisting of patients with a single primary cancer (single primary) and another group consisting of patients with synchronous multiple primaries, and the incidences of postoperative complications and lymph node metastasis were retrospectively compared between the two groups. RESULTS f the 145 patients, 107 had a single primary cancer and 38 had multiple primaries. There was no significant difference in the age, sex, or rate of intraepithelial cancer between the two groups. Postoperative complications included dysphagia in 6 (5.6%) patients with a single primary and 2 (5.3%) patients with multiple primaries. One patient with multiple primaries required gastrostomy because of aspiration pneumonia. In addition, the following complications were also observed. Laryngeal paralysis occurred in 2 (1.9%) patients with a single primary, and 1 (2.6%) patient with multiple primaries; tracheostomy because of postoperative bleeding in 1 (0.9%) patient with a single primary; infection occurred in 2 (5.3%) patients with multiple primaries. Postoperative lymph node metastasis was found in 7 (6.5%) patients with a single primary and 6 (15.8%) patients with multiple primaries. Lymphatic invasion of the primary cancer was noted in 3 (2.8%) patients with a single primary and 5 (13.2%) patients with multiple primaries, being significantly higher in the latter group. CONCLUSION ELPS is also a safe surgery for patients with multiple primaries. However, the incidence of lymphatic invasion of the primary cancer was significantly higher in patients with multiple primaries.
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Affiliation(s)
- Kazuchika Ohno
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
| | - Kenro Kawada
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Taro Sugimoto
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan; Department of Otolaryngology, Head and Neck Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Yusuke Kiyokawa
- Department of Otolaryngology, Head and Neck Surgery, Japanese Red Cross Musasiho Hospital, Tokyo, Japan
| | - Hiroaki Kawabe
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryosuke Takahashi
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nobuaki Koide
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yumiko Tateishi
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Akihisa Tasaki
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yosuke Ariizumi
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takahiro Asakage
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
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21
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Tamashiro A, Yoshio T, Ishiyama A, Tsuchida T, Hijikata K, Yoshimizu S, Horiuchi Y, Hirasawa T, Seto A, Sasaki T, Fujisaki J, Tada T. Artificial intelligence-based detection of pharyngeal cancer using convolutional neural networks. Dig Endosc 2020; 32:1057-1065. [PMID: 32064684 DOI: 10.1111/den.13653] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 02/13/2020] [Accepted: 02/14/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES The prognosis for pharyngeal cancer is relatively poor. It is usually diagnosed in an advanced stage. Although the recent development of narrow-band imaging (NBI) and increased awareness among endoscopists have enabled detection of superficial pharyngeal cancer, these techniques are still not prevalent worldwide. Nevertheless, artificial intelligence (AI)-based deep learning has led to significant advancements in various medical fields. Here, we demonstrate the diagnostic ability of AI-based detection of pharyngeal cancer from endoscopic images in esophagogastroduodenoscopy. METHODS We retrospectively collected 5403 training images of pharyngeal cancer from 202 superficial cancers and 45 advanced cancers from the Cancer Institute Hospital, Tokyo, Japan. Using these images, we developed an AI-based diagnostic system with convolutional neural networks. We prepared 1912 validation images from 35 patients with 40 pharyngeal cancers and 40 patients without pharyngeal cancer to evaluate our system. RESULTS Our AI-based diagnostic system correctly detected all pharyngeal cancer lesions (40/40) in the patients with cancer, including three small lesions smaller than 10 mm. For each image, the AI-based system correctly detected pharyngeal cancers in images obtained via NBI with a sensitivity of 85.6%, much higher sensitivity than that for images obtained via white light imaging (70.1%). The novel diagnostic system took only 28 s to analyze 1912 validation images. CONCLUSIONS The novel AI-based diagnostic system detected pharyngeal cancer with high sensitivity. It could facilitate early detection, thereby leading to better prognosis and quality of life for patients with pharyngeal cancers in the near future.
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Affiliation(s)
- Atsuko Tamashiro
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiyuki Yoshio
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Tada Tomohiro Institute of Gastroenterology and Proctology, Saitama, Japan
| | - Akiyoshi Ishiyama
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Tsuchida
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kazunori Hijikata
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shoichi Yoshimizu
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yusuke Horiuchi
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiaki Hirasawa
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Tada Tomohiro Institute of Gastroenterology and Proctology, Saitama, Japan
| | - Akira Seto
- Department of, Head and Neck, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toru Sasaki
- Department of, Head and Neck, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Junko Fujisaki
- Department of, Departments of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Tada
- AI Medical Service Inc., Tokyo, Japan.,Tada Tomohiro Institute of Gastroenterology and Proctology, Saitama, Japan
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22
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Distal gastrectomy for early gastric conduit carcinoma after Ivor-Lewis esophagectomy. Gen Thorac Cardiovasc Surg 2020; 69:405-408. [PMID: 33034822 DOI: 10.1007/s11748-020-01506-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 09/28/2020] [Indexed: 10/23/2022]
Abstract
A metachronous neoplasm can develop in a gastric conduit used for reconstruction after esophagectomy for thoracic esophageal cancer. Surgical resection is sometimes necessary to treat this neoplasm. We report a method for performing minimally invasive gastrectomy with preservation of the proximal residual stomach through laparotomy for cancer in the distal side of gastric conduit after Ivor-Lewis esophagectomy. Furthermore, Roux-en-Y reconstruction was performed after gastrectomy. This minimally invasive partial gastrectomy for early gastric conduit cancer and followed Roux-en-Y reconstruction may lead to a favorable clinical outcome.
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23
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Katada C, Yokoyama T, Yano T, Oda I, Shimizu Y, Takemura K, Koike T, Takizawa K, Hirao M, Okada H, Nakayama N, Kubota Y, Matsuo Y, Kawakubo H, Ishikawa H, Yokoyama A, Muto M. Association between the findings of metachronous secondary primary malignancies and the number of Lugol-voiding lesions. Dis Esophagus 2020; 33:5734967. [PMID: 32052025 DOI: 10.1093/dote/doz110] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 10/18/2019] [Accepted: 12/21/2019] [Indexed: 12/11/2022]
Abstract
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.
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Affiliation(s)
- Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Tetsuji Yokoyama
- Department of Health Promotion, National Institute of Public Health, Wako, Japan
| | - Tomonori Yano
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yuichi Shimizu
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Kenichi Takemura
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Norisuke Nakayama
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Yutaro Kubota
- Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Yasumasa Matsuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Hirofumi Kawakubo
- Department of Endoscopy Center, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Yokoyama
- Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Japan
| | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
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24
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Hirohashi K, Ohashi S, Amanuma Y, Nakai Y, Ida T, Baba K, Mitani Y, Mizumoto A, Yamamoto Y, Kikuchi O, Matsubara J, Yamada A, Miyamoto S, Seno H, Matsuda T, Muto M. Protective effects of Alda-1, an ALDH2 activator, on alcohol-derived DNA damage in the esophagus of human ALDH2*2 (Glu504Lys) knock-in mice. Carcinogenesis 2020; 41:194-202. [PMID: 31074772 PMCID: PMC7175241 DOI: 10.1093/carcin/bgz091] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Revised: 04/15/2019] [Accepted: 05/09/2019] [Indexed: 12/15/2022] Open
Abstract
Alcohol consumption is the key risk factor for the development of esophageal squamous cell carcinoma (ESCC), and acetaldehyde, a metabolite of alcohol, is an alcohol-derived major carcinogen that causes DNA damage. Aldehyde dehydrogenase2 (ALDH2) is an enzyme that detoxifies acetaldehyde, and its activity is reduced by ALDH2 gene polymorphism. Reduction in ALDH2 activity increases blood, salivary and breath acetaldehyde levels after alcohol intake, and it is deeply associated with the development of ESCC. Heavy alcohol consumption in individuals with ALDH2 gene polymorphism significantly elevates the risk of ESCC; however, effective prevention has not been established yet. In this study, we investigated the protective effects of Alda-1, a small molecule ALDH2 activator, on alcohol-mediated esophageal DNA damage. Here, we generated novel genetically engineered knock-in mice that express the human ALDH2*1 (wild-type allele) or ALDH2*2 gene (mutant allele). Those mice were crossed, and human ALDH2*1/*1, ALDH2*1/*2 and ALDH2*2/*2 knock-in mice were established. They were given 10% ethanol for 7 days in the presence or absence of Alda-1, and we measured the levels of esophageal DNA damage, represented by DNA adduct (N2-ethylidene-2′-deoxyguanosine). Alda-1 significantly increased hepatic ALDH2 activity both in human ALDH2*1/*2 and/or ALDH2*2/*2 knock-in mice and reduced esophageal DNA damage levels after alcohol drinking. Conversely, cyanamide, an ALDH2-inhibitor, significantly exacerbated esophageal DNA adduct level in C57BL/6N mice induced by alcohol drinking. These results indicate the protective effects of ALDH2 activation by Alda-1 on esophageal DNA damage levels in individuals with ALDH2 gene polymorphism, providing a new insight into acetaldehyde-mediated esophageal carcinogenesis and prevention.
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Affiliation(s)
- Kenshiro Hirohashi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Shinya Ohashi
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Yusuke Amanuma
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Yukie Nakai
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Tomomi Ida
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Kiichiro Baba
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Yosuke Mitani
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Ayaka Mizumoto
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Yoshihiro Yamamoto
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Osamu Kikuchi
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Junichi Matsubara
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Atsushi Yamada
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Shin’ichi Miyamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
| | - Tomonari Matsuda
- Research Center for Environmental Quality Management, Kyoto University, Yumihama, Otsu, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan
- To whom correspondence should be addressed. Tel: +81 75 751 4592; Fax:+81 75 751 4594;
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25
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Yokoyama A, Katada C, Yokoyama T, Takizawa K, Yano T, Oda I, Shimizu Y, Nakanishi H, Koike T, Hirao M, Okada H, Yoshii T, Katagiri A, Yamanouchi T, Matsuo Y, Kawakubo H, Kobayashi N, Ishikawa H, Muto M. The Alcohol Use Disorders Identification Test and the risk of metachronous cancer after endoscopic resection of esophageal cancer. Carcinogenesis 2020; 41:1049-1056. [PMID: 32157279 DOI: 10.1093/carcin/bgaa022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 02/10/2020] [Accepted: 03/06/2020] [Indexed: 12/15/2022] Open
Abstract
Follow-up studies of Japanese patients who had undergone endoscopic resection (ER) for early esophageal squamous cell carcinoma (ESCC) have reported a high prevalence of metachronous SCC in the upper aerodigestive tract (UAT). This prospective multicenter cohort study followed up 330 Japanese patients after ER of ESCC for a median of 49.4 months. The Alcohol Use Disorders Identification Test (AUDIT) for the 12-month period prior to study registration revealed high frequencies of high-risk drinking behaviors: 84 (25.4%) subjects had AUDIT scores of ≥15 points (suspected alcohol dependence) and 121 (36.7%) subjects had AUDIT scores of 8-14 points (hazardous drinking). Seventy-four subjects were metachronously diagnosed with ESCC, and 20 subjects with head and neck SCC (HNSCC). AUDIT scores ≥15 were associated with increases in the total number of HNSCCs per 100 person-years (0.4 for 0-7, 1.2 for 8-14 and 7.1 for ≥15; P < 0.0001). AUDIT scores were progressively associated with the grade of esophageal Lugol-voiding lesions (LVLs), a predictor of field cancerization in the UAT. Both an AUDIT score of ≥15 points and the presence of multiple LVLs were independent predictors of metachronous HNSCC [multivariate hazard ratio (95% confidence interval) = 6.98 (1.31-37.09) and 3.19 (1.19-8.54), respectively]. However, a high AUDIT score was not a predictor of metachronous ESCC. In conclusion, high AUDIT scores were markedly frequent in this population and increased the risk of metachronous HNSCC. The assessment of drinking behavior using the AUDIT and the completion of interventions for alcohol problems should be incorporated into the treatment strategy of ESCC. The name of the clinical trial register and the clinical trial registration number: Japan Esophageal Cohort Study, UMIN000001676.
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Affiliation(s)
- Akira Yokoyama
- Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Tetsuji Yokoyama
- Department of Health Promotion, National Institute of Public Health, Wako, Saitama, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Shizuoka, Japan
| | - Tomonori Yano
- Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Tokyo, Japan
| | - Yuichi Shimizu
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaidō, Japan
| | - Hiroyoshi Nakanishi
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Osaka, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan
| | - Takako Yoshii
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Atsushi Katagiri
- Department of Medicine, Division of Gastroenterology, Showa University Hospital, Tokyo, Tokyo, Japan
| | - Takenori Yamanouchi
- Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Kumamoto, Japan
| | - Yasumasa Matsuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan
| | - Nozomu Kobayashi
- Department of Gastroenterology, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan
| | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Kyoto, Japan
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26
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Thakur K, Singh CA, Thakar A, Kakkar A, Sikka K, Kumar R, Sharma SC. Prevalence of Synchronous ESCN in Head and Neck Cancer: A Single-Institution Perspective. Laryngoscope 2020; 131:E807-E814. [PMID: 32619324 DOI: 10.1002/lary.28821] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/13/2020] [Accepted: 05/19/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVES The primary objective was to determine the prevalence of synchronous esophageal squamous cell carcinoma in head and neck squamous cell carcinoma (HNSCC) patients. The secondary objective was to determine risk factors for the development of synchronous esophageal squamous cell carcinoma (ESCN). STUDY DESIGN Cross sectional observation study. METHODS A prospective cross sectional, observational study on consecutive 300 newly diagnosed oral cavity, oropharynx, hypopharynx, and laryngeal squamous cell carcinoma patients who underwent trans-nasal esophageal endoscopy with white light imaging and narrow band imaging. RESULTS Among 300 patients, index HNSCCs were located in the oral cavity (n = 154, 51.3%), oropharynx (n = 63, 21%), larynx (n = 53, 17.7%), and hypopharynx (n = 30, 10%). The prevalence of synchronous ESCN was 2.7% (n = 8), including four low-grade, two high-grade dysplasia, and two squamous cell carcinomas. On logistic regression analysis, moderate to heavy alcohol consumption (OR 8.7, P = .01) and primary HNSCC involving supraglottis [(OR 12.5, P = .02) were risk factors for synchronous ESCN. The association of pyriform sinus carcinoma and synchronous ESCN was of borderline significance (P = .054, OR 10.92). CONCLUSION The prevalence of synchronous ESCN in HNSCC was 2.7%. Routine trans-nasal esophagoscopy should be performed in all newly diagnosed patients with carcinoma of the supraglottis and pyriform sinus, and those with consumption of moderate to heavy alcohol for the screening of synchronous ESCN. LEVEL OF EVIDENCE 2b Laryngoscope, 131:E807-E814, 2021.
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Affiliation(s)
- Kuldeep Thakur
- Department of Otolaryngology, Head and Neck Surgery, All India Institute of Medical Sciences New Delhi, Delhi, India
| | - Chirom A Singh
- Department of Otolaryngology, Head and Neck Surgery, All India Institute of Medical Sciences New Delhi, Delhi, India
| | - Alok Thakar
- Department of Otolaryngology, Head and Neck Surgery, All India Institute of Medical Sciences New Delhi, Delhi, India
| | - Aanchal Kakkar
- Department of Pathology, All India Institute of Medical Sciences New Delhi, Delhi, India
| | - Kapil Sikka
- Department of Otolaryngology, Head and Neck Surgery, All India Institute of Medical Sciences New Delhi, Delhi, India
| | - Rajeev Kumar
- Department of Otolaryngology, Head and Neck Surgery, All India Institute of Medical Sciences New Delhi, Delhi, India
| | - Suresh C Sharma
- Department of Otolaryngology, Head and Neck Surgery, All India Institute of Medical Sciences New Delhi, Delhi, India
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27
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Hoxhaj I, Hysaj O, Vukovic V, Leoncini E, Amore R, Pastorino R, Boccia S. Occurrence of metachronous second primary cancer in head and neck cancer survivors: A systematic review and meta-analysis of the literature. Eur J Cancer Care (Engl) 2020; 29:e13255. [PMID: 32400912 DOI: 10.1111/ecc.13255] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 12/27/2019] [Accepted: 04/16/2020] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Head and neck cancer (HNC) is the sixth leading cancer worldwide with approximately 600,000 new cases per year. Several studies suggest that HNC survivors may have an increased risk of developing second primary cancers (SPCs). A systematic review and meta-analysis was performed aiming to quantify the overall and site-specific risk of metachronous SPCs in HNC survivors. METHODS PubMed, Web of Science and Scopus were searched to identify studies published until October 2019. Studies investigating the standardised incidence ratio (SIR) of metachronous SPC were included. A random-effects meta-analysis was performed to calculate the overall and site-specific SIRs. Newcastle-Ottawa Scale was used to assess the study's quality. Heterogeneity was quantified using the I2 statistics and explored using meta-regression. RESULTS Twenty-six studies were included in the systematic review. Studies differed by the definition of metachronous SPC used. For the meta-analyses, the studies were grouped according to these definitions. In the three groups, the overall risk of metachronous SPC was increased. The highest SPC risk was for oropharynx, oesophagus and lung. CONCLUSIONS Head and neck cancer survivors are at increased overall risk of metachronous SPCs. The canonical upper aerodigestive sites, HNLE (head and neck, oesophagus and lung), were the SPC sites with the highest risk. IMPLICATION FOR CANCER SURVIVORS Our results emphasise the importance of targeted surveillance strategies aimed at early detection and tertiary preventive interventions.
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Affiliation(s)
- Ilda Hoxhaj
- Sezione di Igiene, Dipartimento Universitario di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Ola Hysaj
- Sezione di Igiene, Dipartimento Universitario di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Vladimir Vukovic
- Sezione di Igiene, Dipartimento Universitario di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Roma, Italia.,Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy
| | - Emanuele Leoncini
- Sezione di Igiene, Dipartimento Universitario di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Rosarita Amore
- Sezione di Igiene, Dipartimento Universitario di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Roma, Italia
| | - Roberta Pastorino
- Department of Woman and Child Health and Public Health-Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
| | - Stefania Boccia
- Sezione di Igiene, Dipartimento Universitario di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Roma, Italia.,Department of Woman and Child Health and Public Health-Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia
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28
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Kuwabara H, Chiba H, Tachikawa J, Okada N, Ashikari K, Arimoto J, Nakaoka M, Sakai E, Goto T, Ohata K. Clinical characteristic of esophageal cancer without lugol-voiding lesions in the background esophagus. Dig Endosc 2020; 32:621-627. [PMID: 31965622 DOI: 10.1111/den.13631] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 01/15/2020] [Accepted: 01/16/2020] [Indexed: 02/08/2023]
Abstract
Lugol chromoendoscopy is useful for the detection of early esophageal squamous cell cancer (ESCC). Multiple lugol-voiding lesions (LVLs) on lugol chromoendoscopy are associated with a very high risk of multiple cancers arising in the esophagus. Due to the widespread use of narrow band image technology in many institutions, esophageal cancer without LVLs in the background esophagus is sometimes detected. This retrospective study aims to clarify the clinical characteristic of esophageal cancer without LVLs in the background esophagus. A total of 191 consecutive patients with 204 ESCCs had undergone endoscopic submucosal dissection (ESD) from 2011 and 2014. Amongst these lesions, the number of LVLs in the background esophagus per endoscopic view was counted excluding main lesion, and the grading was divided into no LVLs ESCC (nL-ESCC) group and LVLs ESCC (L-ESCC) group. This study evaluated the clinical characteristics and the cumulative incidence of metachronous ESCC after ESD in both groups. Thirty-six patients with 36 lesions and 155 patients with 168 lesions were separated into the nL-ESCC group and L-ESCC group, respectively. On multivariate analysis, the nL-ESCC group was found to be more common in females, who were non-drinkers, or with erosive esophagitis. During follow-up periods, the cumulative incidence of metachronous ESCC at 3-years was 14.4% and 0.00% in the L-ESCC and nL-ESCC groups, respectively (P < 0.01). Our study showed that esophageal cancer without LVLs in the background esophagus was mostly occurred in females, who were non-drinkers, or with erosive esophagitis, which are uncommon features of ESCC.
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Affiliation(s)
- Hiroki Kuwabara
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Hideyuki Chiba
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Jun Tachikawa
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Naoya Okada
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Keiichi Ashikari
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Kanagawa, Japan
| | - Jun Arimoto
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Michiko Nakaoka
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Eiji Sakai
- Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan
| | - Toru Goto
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Ken Ohata
- Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan
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29
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Gotoda T, Kanzaki H, Okamoto Y, Obayashi Y, Baba Y, Hamada K, Sakae H, Abe M, Iwamuro M, Kawano S, Kawahara Y, Okada H. Tolerability and efficacy of the concentration of iodine solution during esophageal chromoendoscopy: a double-blind randomized controlled trial. Gastrointest Endosc 2020; 91:763-770. [PMID: 31669091 DOI: 10.1016/j.gie.2019.10.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 10/03/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Esophageal chromoendoscopy with iodine solution is an important diagnostic method for the detection of superficial esophageal cancer. However, the concentration of iodine solution has differed among reports. This study aimed to evaluate patient discomfort with different iodine concentrations. METHODS We performed a prospective, double-blind, randomized study. We prospectively enrolled and analyzed 77 patients who were at high risk for esophageal carcinoma and scheduled to undergo EGD from March 2018 to January 2019. All patients were divided into 2 groups before the procedure to compare pain measurements: a 1% iodine solution group (group A) and a 2% iodine solution group (group B). The primary endpoint of this study was the difference in pain measurement between 1% and 2% iodine solution chromoendoscopy. Secondary endpoints were safety, detection yield, and color evaluation based on both the endoscopist's survey and color values, as determined using the Commission Internationale de l'Eclairage (CIELAB, Vienna, Austria) color evaluation system, in the iodine-faded and iodine-stained area of each group. RESULTS Heartburn and retrosternal pain in group A were significantly lower than those in group B (P = .02). Eleven patients reported heartburn and retrosternal pain (group A, 2; group B, 9). Four patients reported pain above the sternal angle and 7 below the sternal angle. There was no significant difference between the 2 groups with regard to detection yield, color evaluation by the endoscopist's assessment, or color values. No patients had any adverse events, and all safely completed this study. CONCLUSIONS The 2% iodine solution resulted in significantly greater pain than the 1% iodine solution, and the color of the stained esophageal images of each group was the same from this study. Therefore, the 1% iodine solution is recommended for esophageal chromoendoscopy. (Clinical trial registration number: UMIN 000029796.).
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Affiliation(s)
- Tatsuhiro Gotoda
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiromitsu Kanzaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yuki Okamoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yuka Obayashi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yuki Baba
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kenta Hamada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Sakae
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Makoto Abe
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Seiji Kawano
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshiro Kawahara
- Department of Endoscopy, Okayama University Hospital, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Department of Endoscopy, Okayama University Hospital, Okayama, Japan
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30
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Mitani S, Kadowaki S, Oze I, Masuishi T, Narita Y, Bando H, Oonishi S, Hirayama Y, Tanaka T, Tajika M, Koide Y, Kodaira T, Abe T, Muro K. Risk of second primary malignancies after definitive treatment for esophageal cancer: A competing risk analysis. Cancer Med 2019; 9:394-400. [PMID: 31730285 PMCID: PMC6943156 DOI: 10.1002/cam4.2688] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Revised: 09/26/2019] [Accepted: 10/20/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Esophageal cancer is associated with synchronous or metachronous cancer at other primary sites. However, few studies have evaluated the second malignancies after the treatment of esophageal cancer. The present study aimed to clarify the frequency of and risk factors for the second malignancies after definitive therapy for esophageal cancer. PATIENTS AND METHODS We included patients with esophageal cancer who received definitive therapy between 2000 and 2010. Exclusion criteria were synchronous cancer or a past history of cancer. Standardized incidence rate (SIR) was calculated using age- and sex-specific incidence rates from the cancer registry data. To conduct risk analyses, we used the competing risk regression model, which defined death and the development of second malignancies as competing risks. RESULTS A total of 758 patients were included, with 131 second malignancies occurring in 106 patients (14%), over a median follow-up of 3.7 years. Cumulative incidences of second malignancies after 3, 5, and 8 years were 4.0%, 7.6%, and 13.8%, respectively. The risk of second malignancy was significantly elevated [SIR = 1.83, 95% confidence interval (CI): 1.50-2.22]. The most common sites of primary tumor were the head and neck (20%), followed by the lung (17%), stomach (16%), colon and rectum (11%), and urinary tract (9%). Risk analyses revealed that age ≥ 65 years [subdistribution hazard ratio (sHR): 1.51, 95% CI: 1.01-2.24, vs age < 65] and clinical stages 0-I (sHR: 2.48, 95% CI: 1.46-4.22, vs stage III and IV) and II (sHR: 2.10, 95% CI: 1.23-3.58, vs stage III and IV) were significantly associated with second malignancies. CONCLUSIONS Compared with the general population, an increased incidence of second malignancies was observed in the patients with esophageal cancer in the present study even after definitive treatment. Careful follow-up is required, especially in patients at a higher risk of second malignancies.
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Affiliation(s)
- Seiichiro Mitani
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.,Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Shigenori Kadowaki
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Isao Oze
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan
| | - Toshiki Masuishi
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yukiya Narita
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hideaki Bando
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Sachiyo Oonishi
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yutaka Hirayama
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tsutomu Tanaka
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Masahiro Tajika
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yutaro Koide
- Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takeshi Kodaira
- Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tetsuya Abe
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
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31
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Araki K, Tomifuji M, Shiotani A, Hirano S, Yokoyama J, Tsukahara K, Homma A, Yoshimoto S, Hasegawa Y. Minimally invasive surgery for laryngopharyngeal cancer: Multicenter feasibility study of a combination strategy involving transoral surgery and real‐time indocyanine green fluorescence‐navigated sentinel node navigation surgery. Head Neck 2019; 42:254-261. [DOI: 10.1002/hed.25993] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 09/03/2019] [Accepted: 10/09/2019] [Indexed: 02/05/2023] Open
Affiliation(s)
- Koji Araki
- Department of Otolaryngology—Head and Neck SurgeryNational Defense Medical College Tokorozawa Japan
| | - Masayuki Tomifuji
- Department of Otolaryngology—Head and Neck SurgeryNational Defense Medical College Tokorozawa Japan
| | - Akihiro Shiotani
- Department of Otolaryngology—Head and Neck SurgeryNational Defense Medical College Tokorozawa Japan
| | - Shigeru Hirano
- Department of Otolaryngology—Head and Neck SurgeryKyoto Prefectural University of Medicine Kyoto Japan
| | - Junkichi Yokoyama
- Department of Otolaryngology—Head and Neck SurgeryEdogawa Hospital Tokyo Japan
| | - Kiyoaki Tsukahara
- Department of Otorhinolaryngology—Head and Neck SurgeryTokyo Medical University Tokyo Japan
| | - Akihiro Homma
- Department of Otolaryngology—Head and Neck Surgery, Faculty of Medicine and Graduate School of MedicineHokkaido University Sapporo Japan
| | - Seichi Yoshimoto
- Department of Head and Neck SurgeryNational Cancer Center Hospital Tokyo Japan
| | - Yasuhisa Hasegawa
- Department of Head and Neck Surgery and OtolaryngologyAsahi University Hospital Gifu Japan
- Department of Head and Neck SurgeryAichi Cancer Center Hospital Nagoya Japan
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32
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Katada C, Horimatsu T, Muto M, Tanaka K, Matsuda K, Fujishiro M, Saito Y, Ohtsuka K, Oda I, Kato M, Kida M, Kobayashi K, Hoteya S, Kodashima S, Matsuda T, Yamamoto H, Ryozawa S, Iwakiri R, Kutsumi H, Miyata H, Kato M, Haruma K, Fujimoto K, Uemura N, Kaminishi M, Tajiri H. Current status of esophageal endoscopy including the evaluation of smoking and alcohol consumption in Japan: an analysis based on the Japan endoscopy database. Esophagus 2019; 16:174-179. [PMID: 30519821 DOI: 10.1007/s10388-018-0650-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 11/20/2018] [Indexed: 02/03/2023]
Abstract
PURPOSE The aim was to investigate the current status of esophageal endoscopy, including the evaluation of smoking and alcohol consumption, in Japan. METHODS A total of 47,441 patients who underwent 69,748 sessions of esophageal endoscopy were registered in the Japan Endoscopy Database between January 2015 and March 2017. The study variables were as follows: (1) methods for monitoring the esophagus and the time required for monitoring and (2) the status of smoking and alcohol consumption in patients with esophageal cancer and head and neck cancer. RESULTS Image-enhanced endoscopy was performed in 10.6%, Lugol chromoendoscopy in 4.1%, and magnifying endoscopy in 3.2%. The mean time required for gastrointestinal endoscopy was 10 min 58 s. The mean examination times in patients with or without monitoring of the head and neck were 10 min 51 s and 11 min 13 s, respectively. In 57.0% of the patients with esophageal cancer, the head and neck were monitored at the time of gastrointestinal endoscopy. The proportion of current smokers (esophageal cancer: 16.8-4.7%; head and neck cancer: 24.3-9.3%) and addicted drinkers (esophageal cancer: 52.3-40.8%; head and neck cancer: 50.2-47.3%) were lower at the second or subsequent endoscopy than at the initial endoscopy. CONCLUSIONS The new strategy for esophageal endoscopy has led to an evolutionary change in Japan. The patients with esophageal cancer and head and neck cancer who underwent a second or subsequent endoscopy had lower incidences of smoking and alcohol consumption, although the incidences remained high.
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Affiliation(s)
- Chikatoshi Katada
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan. .,Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, 252-0374, Japan.
| | - Takahiro Horimatsu
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Manabu Muto
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Kiyohito Tanaka
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan.,JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Koji Matsuda
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan.,JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan.,JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Yutaka Saito
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan.,JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Kazuo Ohtsuka
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Ichiro Oda
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Masayuki Kato
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Mitsuhiro Kida
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Kiyonori Kobayashi
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Shu Hoteya
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Shinya Kodashima
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Takahisa Matsuda
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Hironori Yamamoto
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Shomei Ryozawa
- MSED-J (Minimal Standard Endoscopic Database) Creation Subcommittee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Ryuichi Iwakiri
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Hiromu Kutsumi
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Hiroaki Miyata
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Mototsugu Kato
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Ken Haruma
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Kazuma Fujimoto
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Naomi Uemura
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Michio Kaminishi
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Hisao Tajiri
- JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan
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Yu X, van Munster SN, Zhang Y, Xue L, Fleischer DE, Weusten BLAM, Lu N, Dawsey SSM, Bergman JJGHM, Wang G. Durability of radiofrequency ablation for treatment of esophageal squamous cell neoplasia: 5-year follow-up of a treated cohort in China. Gastrointest Endosc 2019; 89:736-748.e2. [PMID: 30905354 PMCID: PMC7517876 DOI: 10.1016/j.gie.2018.10.030] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 10/19/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Radiofrequency ablation (RFA) is an accepted treatment for flat Barrett's neoplasia. Less is known about RFA for esophageal squamous cell neoplasia (ESCN). Our group has reported several prospective studies of RFA for ESCN in China with promising results through 12 months of follow-up. In this cohort study we aimed to evaluate longer term outcomes after RFA for ESCN. METHODS Patients with flat unstained lesions (USLs) on Lugol's endoscopy containing moderate-/high-grade intraepithelial neoplasia (MGIN/HGIN) or mucosal cancer were treated with RFA every 3 months until complete remission (CR; no MGIN or a worse histologic grade). Patients with CR at 12 months (CR12) were included for follow-up and underwent annual Lugol's endoscopy with biopsy sampling and re-RFA for flat USLs. The clinical course of patients with persistent ESCN at 12 months (treatment failures) is also reported. RESULTS Among the 78 patients in CR12, 67 (86%) had sustained CR during a median of 48 months (interquartile range, 48-48) of follow-up and 5 endoscopies (interquartile range, 4-6). Recurrence occurred in 7 of 78 patients (9%; MGIN, n = 6; HGIN, n = 1); all lesions were managed with RFA. Four other patients (5%) had progression (to HGIN, n = 1; submucosal esophageal squamous cell carcinoma, n = 3). During follow-up protocol violations occurred in 46 of 78 patients (59%). Of the 12 treatment failures, progression occurred in 6. Overall, 2 patients developed subepithelial disease that was not visible after Lugol's endoscopy. Based on post-hoc analysis, the pink-color sign at baseline (a pink color change after Lugol's endoscopy) significantly predicted failure after RFA. CONCLUSIONS RFA is relatively easy to apply and can efficiently treat large areas with ESCN. Despite protocol violations that may have interfered with the efficacy of RFA in 59% of patients, most patients with CR12 had sustained CR during follow-up. However, some patients progressed to advanced disease and 2 developed subepithelial disease, not visible after Lugol's endoscopy. Based on currently available data, we advise the restriction of the use of RFA for flat MGIN and HGIN without the pink-color sign on Lugol's chromoendoscopy. (Clinical trial registration number: NCT02047305.).
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Affiliation(s)
- Xinying Yu
- Department of Endoscopy, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Sanne N van Munster
- Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Yueming Zhang
- Department of Endoscopy, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Liyan Xue
- Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - David E Fleischer
- Department of Gastroenterology & Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Bas L A M Weusten
- Department of Gastroenterology & Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Gastroenterology & Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Ning Lu
- Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Sanford S M Dawsey
- Department of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Jacques J G H M Bergman
- Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Guiqi Wang
- Department of Endoscopy, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China
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Petroianu A, Sabino KR, Nunes MB. Synchronous triple squamous cell carcinoma of the esophagus. Int J Surg Case Rep 2018; 49:34-36. [PMID: 29966947 PMCID: PMC6039883 DOI: 10.1016/j.ijscr.2018.05.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 05/28/2018] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Synchronous multiple primary malignancies of the esophagus and other organs are relatively unusual, but only five articles have published two synchronous cancers, both in the esophagus. This is the first published case of a triple esophageal carcinoma. CASE REPORT A 43-year-old man was referred to our hospital with severe progressive dysphagia and epigastric pain for almost one year. Endoscopy and imaging exams revealed three tumors located in upper, middle and lower esophagus. The upper and middle esophageal cancers were irresectable, and the patient was treated with radio- and chemotherapy. He survived 11 months after the diagnosis and died due to severe undernutrition and bilateral pneumonia. CONCLUSION In presence of squamous cell carcinoma of the esophagus, propedeutics should be carefully performed in order to verify the occurrence of other synchronous tumors in the esophagus and other organs, mainly head and neck and bronchial regions.
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Affiliation(s)
- Andy Petroianu
- Department of Surgery, School of Medicine, Federal University, Minas Gerais, Brazil.
| | - Kelly Renata Sabino
- Department of Surgery, School of Medicine, Federal University, Minas Gerais, Brazil
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Avinçsal MO, Shinomiya H, Teshima M, Kubo M, Otsuki N, Kyota N, Sasaki R, Zen Y, Nibu KI. Impact of alcohol dehydrogenase-aldehyde dehydrogenase polymorphism on clinical outcome in patients with hypopharyngeal cancer. Head Neck 2017; 40:770-777. [PMID: 29286190 DOI: 10.1002/hed.25050] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 09/04/2017] [Accepted: 11/16/2017] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND The purpose of this research was to investigate the association between alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms and hypopharyngeal squamous cell carcinoma (SCC) survival. METHODS We genotyped ADH1B (rs1229984) and ALDH2 (rs671) single nucleotide polymorphisms (SNPs) in 85 Japanese male patients with hypopharyngeal SCC. The independent prognostic values of ADH1B-ALDH2 genotypes were analyzed by univariate and multivariate proportional hazard Cox regression, taking well-known clinical risk factors into account. RESULTS Heavy drinkers with ALDH2*2 allele resulted in significantly worse overall survival (OS; P = .028) and disease-free survival (DFS; P = .029) compared with other patients. Heavy drinkers with ALDH2*2 allele remained statistically significant in multivariate analysis for OS and DFS, indicating independent poor prognostic factor (hazard ratio [HR] 2.251; 95% confidence interval [CI] 1.018-4.975 and HR 2.261; 95% CI 1.021-5.006, respectively). CONCLUSION We conclude that heavy drinkers with the ALDH2*2 allele are associated with poor outcome in hypopharyngeal SCC.
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Affiliation(s)
- Mehmet Ozgur Avinçsal
- Department of Otolaryngology - Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.,Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hirotaka Shinomiya
- Department of Otolaryngology - Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masanori Teshima
- Department of Otolaryngology - Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Mie Kubo
- Department of Otolaryngology - Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Naoki Otsuki
- Department of Otolaryngology - Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Naomi Kyota
- Department of Medical Oncology and Hematology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryohei Sasaki
- Department of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoh Zen
- Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ken-Ichi Nibu
- Department of Otolaryngology - Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Simões CA, Durazzo MD, de Aquino Xavier FC, Gallottini MHC, Lourenço SV, Pinto Júnior DDS, Magacho de Andrade NM, Miazaki AP, Dedivitis RA, Cernea CR. Lugol Chromoscopy in the Follow-up of Head and Neck Carcinoma. Ann Maxillofac Surg 2017; 7:188-193. [PMID: 29264284 PMCID: PMC5717893 DOI: 10.4103/ams.ams_95_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Introduction: Lugol is helpful in identifying early second primary tumors (SPTs) during oroscopy and pharyngoscopy, but this technique has not been assessed during follow-up visits with these patients. Aim: The aim of this study is to describe the use of Lugol (a low-cost method) to diagnose SPTs in the oral cavity and oropharynx. Methods: Patients treated for squamous cell carcinoma of the head and neck were randomly assigned to two groups. Group A was examined with routine oroscopy and pharyngoscopy without Lugol, and Group B was examined with routine oroscopy and pharyngoscopy without stain and with Lugol. A total of 211 patients were included during 4 years. Results: Six oral and oropharynx carcinomas were detected in Group A. Eighteen oral and oropharynx carcinomas were detected in Group B, twelve of which were not seen without chromoscopy but were detected with Lugol. Conclusion: Lugol increases the detection of malignant lesions compared to routine examination alone.
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Affiliation(s)
- Cesar Augusto Simões
- Department of Head and Neck Surgery, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Marcelo Doria Durazzo
- Department of Head and Neck Surgery, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | | | | | | | | | | | - Aline Paterno Miazaki
- Department of Head and Neck Surgery, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Rogério Aparecido Dedivitis
- Department of Head and Neck Surgery, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Cláudio Roberto Cernea
- Department of Head and Neck Surgery, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
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Yan S, Wu G. Could ALDH2 *2 be the reason for low incidence and mortality of ovarian cancer for East Asia women? Oncotarget 2017; 9:12503-12512. [PMID: 29552329 PMCID: PMC5844765 DOI: 10.18632/oncotarget.23605] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 12/16/2017] [Indexed: 12/15/2022] Open
Abstract
It is curious that East Asian women have a low incidence and mortality of ovarian cancer in various epidemiological studies. Although different explanations were given, they appear unsubstantial. We notice that East Asian population usually are inactive aldehyde dehydrogenase 2 mutation (ALDH2 * 2) carriers, and ALDH plays an important role in the resistance of ovarian cancer to chemotherapeutics, especially in ovarian cancer stem cells. Therefore, we hypothesize whether ALDH2 mutation is the major reason for low incidence and mortality of ovarian cancer in East Asian women, and use the evidence from literature, transcriptomic data with average 5-year overall survival to confirm our hypothesis.
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Affiliation(s)
- Shaomin Yan
- Bioscience and Technology Research Center, Guangxi Academy of Sciences, Nanning, Guangxi, 530007, China
| | - Guang Wu
- Bioscience and Technology Research Center, Guangxi Academy of Sciences, Nanning, Guangxi, 530007, China
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Łuczaj W, Gęgotek A, Skrzydlewska E. Antioxidants and HNE in redox homeostasis. Free Radic Biol Med 2017; 111:87-101. [PMID: 27888001 DOI: 10.1016/j.freeradbiomed.2016.11.033] [Citation(s) in RCA: 143] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 11/16/2016] [Accepted: 11/17/2016] [Indexed: 12/11/2022]
Abstract
Under physiological conditions, cells are in a stable state known as redox homeostasis, which is maintained by the balance between continuous ROS/RNS generation and several mechanisms involved in antioxidant activity. ROS overproduction results in alterations in the redox homeostasis that promote oxidative damage to major components of the cell, including the biomembrane phospholipids. Lipid peroxidation subsequently generates a diverse set of products, including α,β-unsaturated aldehydes. Of these products, 4-hydroxy-2-nonenal (HNE) is the most studied aldehyde on the basis of its involvement in cellular physiology and pathology. This review summarizes the current knowledge in the field of HNE generation, metabolism, and detoxification, as well as its interactions with various cellular macromolecules (protein, phospholipid, and nucleic acid). The formation of HNE-protein adducts enables HNE to participate in multi-step regulation of cellular metabolic pathways that include signaling and transcription of antioxidant enzymes, pro-inflammatory factors, and anti-apoptotic proteins. The most widely described roles for HNE in the signaling pathways are associated with its activation of kinases, as well as transcription factors that are responsible for redox homeostasis (Ref-1, Nrf2, p53, NFκB, and Hsf1). Depending on its level, HNE exerts harmful or protective effects associated with the induction of antioxidant defense mechanisms. These effects make HNE a key player in maintaining redox homeostasis, as well as producing imbalances in this system that participate in aging and the development of pathological conditions.
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Affiliation(s)
- Wojciech Łuczaj
- Department of Analytical Chemistry, Medical University of Bialystok, Mickiewicza 2d, 15-222 Bialystok, Poland
| | - Agnieszka Gęgotek
- Department of Analytical Chemistry, Medical University of Bialystok, Mickiewicza 2d, 15-222 Bialystok, Poland
| | - Elżbieta Skrzydlewska
- Department of Analytical Chemistry, Medical University of Bialystok, Mickiewicza 2d, 15-222 Bialystok, Poland.
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Lee KD, Wang TY, Lu CH, Huang CE, Chen MC. The bidirectional association between oral cancer and esophageal cancer: A population-based study in Taiwan over a 28-year period. Oncotarget 2017; 8:44567-44578. [PMID: 28562351 PMCID: PMC5546502 DOI: 10.18632/oncotarget.17818] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 04/23/2017] [Indexed: 01/17/2023] Open
Abstract
Previous studies have revealed that patients with oral or esophageal cancer are at higher risk for subsequently developing a second primary malignancy. However, it remains to be determined what association exists between oral cancer and esophageal cancer particularly in Asian countries where squamous cell carcinoma is the predominant type of esophageal cancer. A population-based study was carried out in Taiwan, where the incidence rates of both oral and esophageal squamous cell carcinomas are high, to test the hypothesis that oral cancer or esophageal cancer predisposes an individual to developing the other form of cancer. Our results showed that patients with primary oral cancer (n=45,859) had ten times the risk of second esophageal cancer compared to the general population. Within the same cohort, the reciprocal risk of oral cancer as a second primary in primary esophageal cancer patients (n=16,658) was also increased seven-fold. The bidirectional relationship suggests common risk factors between these two cancers. The present study is not only the first population-based study in Asia to validate the reciprocal relationship between oral and esophageal squamous cell carcinomas, but also will aid in the appropriate selection of high-risk patients for a future follow-up surveillance program.
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Affiliation(s)
- Kuan-Der Lee
- Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ting-Yao Wang
- Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chang-Hsien Lu
- Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Cih-En Huang
- Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Min-Chi Chen
- Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Public Health and Biostatistics Consulting Center, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
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Current status of superficial pharyngeal squamous cell carcinoma in Japan. Int J Clin Oncol 2017; 22:826-833. [PMID: 28501947 DOI: 10.1007/s10147-017-1135-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 05/04/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND To investigate the status and treatment of superficial pharyngeal squamous cell carcinoma in Japan. METHODS We analyzed all cases diagnosed between 2011 and 2013, as recorded in the national database of hospital-based cancer registries. We extracted data on patient sex, age, tumor locations, histology, presentation routes, initial treatments, and TNM stages. Additionally, we compared the characteristics of pharyngeal carcinoma to those of esophageal cancer. RESULTS A total of 16,521 oropharyngeal and hypopharyngeal cancers from 409 institutions were included. Diagnosis of Tis tumors was infrequent, and both cancers were likely to be diagnosed at an advanced stage (n = 866, 5.3%). Tis diseases were the most commonly detected during follow-up examinations for other diseases (n = 608, 70%). While more oropharyngeal Tis patients were men compared to T1-4 patients (88 vs 82%, respectively), hypopharyngeal cancer patients comprised an equally high proportion of men (94 vs 92%, respectively). The most common location of oropharyngeal Tis tumors was the posterior wall (32%), whereas T1-4 tumors were most commonly found on the lateral wall (36%). In hypopharyngeal cancer, both Tis and T1-4 were most commonly located in the pyriform sinus (62%). The proportion of Tis tumors diagnosed at individual institutions showed a positive correlation with the number of endoscopic treatments (r = 0.32, P < 0.001) and the number of esophageal cancer cases (r = 0.37, P < 0.001). CONCLUSION Our national database study elucidated the current characteristics of superficial pharyngeal squamous cell carcinoma patients in Japan. Further improvements in early diagnosis and standardized treatments are warranted.
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Yokoyama A, Katada C, Yokoyama T, Yano T, Kaneko K, Oda I, Shimizu Y, Doyama H, Koike T, Takizawa K, Hirao M, Okada H, Yoshii T, Konishi K, Yamanouchi T, Tsuda T, Omori T, Kobayashi N, Suzuki H, Tanabe S, Hori K, Nakayama N, Kawakubo H, Ishikawa H, Muto M. Alcohol abstinence and risk assessment for second esophageal cancer in Japanese men after mucosectomy for early esophageal cancer. PLoS One 2017; 12:e0175182. [PMID: 28384229 PMCID: PMC5383267 DOI: 10.1371/journal.pone.0175182] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 03/21/2017] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2) and the presence of multiple esophageal Lugol-voiding lesions (LVLs; dysplasia) are strong predictors for multiple development of esophageal squamous cell carcinoma (ESCC) in East Asians. We invented a health risk appraisal (HRA) model for predicting the risk of ESCC based on drinking, smoking, dietary habits, and alcohol flushing, i.e., past or present facial flushing after drinking a glass of beer, a surrogate marker for inactive ALDH2. METHODS Prospective follow-up examinations (median follow-up time, 50.3 months) were performed in 278 Japanese men after endoscopic mucosectomy for early ESCC (UMIN Clinical Trials Registry ID: UMIN000001676). RESULTS Sixty-four subjects developed metachronous ESCC. A receiver operating characteristic curve showed that HRA scores ≥12 best predicted the development of metachronous ESCC. The ESCC detection rate per 100 person-years was 9.8 in the high-HRA-score group (n = 104) and 4.5 in the low-HRA-score group (n = 174), and the risk of development of metachronous ESCC was higher in the high-HRA-score group than in the low-HRA-score group (adjusted hazard ratio: 2.00 [95% CI: 1.12-3.30]). Multiple LVLs was a very strong predictor of the development of metachronous SCC, but high HRA scores predicted it independently. The cumulative incidences of metachronous ESCC decreased after drinking cessation in the high-HRA-score drinker group (adjusted hazard ratio: 0.37 [0.14-0.97]). CONCLUSIONS Both the HRA model that included alcohol flushing and the multiple LVL grade predicted the development of metachronous ESCC in Japanese men after endoscopic mucosectomy for ESCC. Drinking cessation in the high-HRA-score drinker group reduced the rate of metachronous ESCC.
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Affiliation(s)
- Akira Yokoyama
- National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, Japan
| | - Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan
| | - Tetsuji Yokoyama
- Department of Health Promotion, National Institute of Public Health, Saitama, Japan
| | - Tomonori Yano
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Kazuhiro Kaneko
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yuichi Shimizu
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Kokkaido, Japan
| | - Hisashi Doyama
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Takako Yoshii
- Department of Gastroenterology, Kanagawa Cancer Center, Kanagawa, Japan
| | - Kazuo Konishi
- Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Takenori Yamanouchi
- Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Japan
| | - Takashi Tsuda
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Tai Omori
- Endoscopy Center, Kawasaki Municipal Ida Hospital, Kanagawa, Japan
| | - Nozomu Kobayashi
- Department of Diagnostic Imaging, Tochigi Cancer Center, Tochigi, Japan
| | - Haruhisa Suzuki
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Satoshi Tanabe
- Research and Development Center for New Frontiers, Kitasato University School of Medicine, Kanagawa, Japan
| | - Keisuke Hori
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Norisuke Nakayama
- Department of Gastroenterology, Kanagawa Cancer Center, Kanagawa, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Katada C, Yokoyama T, Yano T, Kaneko K, Oda I, Shimizu Y, Doyama H, Koike T, Takizawa K, Hirao M, Okada H, Yoshii T, Konishi K, Yamanouchi T, Tsuda T, Omori T, Kobayashi N, Shimoda T, Ochiai A, Amanuma Y, Ohashi S, Matsuda T, Ishikawa H, Yokoyama A, Muto M. Alcohol Consumption and Multiple Dysplastic Lesions Increase Risk of Squamous Cell Carcinoma in the Esophagus, Head, and Neck. Gastroenterology 2016; 151:860-869.e7. [PMID: 27492616 DOI: 10.1053/j.gastro.2016.07.040] [Citation(s) in RCA: 142] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 07/12/2016] [Accepted: 07/18/2016] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Some patients develop multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract, attributed to field cancerization; alcohol consumption has been associated with this process. We examined the association between multiple areas of dysplastic squamous epithelium with the development of SCC of the esophagus or head and neck cancer, as well as alcohol consumption and smoking. METHODS We examined 331 patients with early stage esophageal SCC using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the esophagus. Patients then were assigned to 3 groups, based on the number of Lugol-voiding lesions: A, no lesion; B, 1-9 lesions; or C, 10 or more lesions. Participants completed lifestyle surveys on their history of drinking, smoking, and diet. All participants were evaluated by laryngopharyngoscopy before registration; only those without head and neck cancer were included, except for patients with superficial SCC limited to the subepithelial layer. Lesions detected in the esophagus and head and neck by surveillance were considered to be metachronous. The study end point was the cumulative incidence of metachronous SCCs in the esophagus and head and neck after endoscopic resection of esophageal SCC, according to the grade of Lugol-voiding lesions. At study entry, all patients were instructed to abstain from alcohol and smoking. RESULTS Over the 2-year study period, metachronous SCCs of the esophagus were detected in 4% of patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in group C (P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs were detected in none of the patients in group A, in 1.7% of the patients in group B, and in 8.6% of the patients in group C (P = .016 for patients in group A vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and neck developed in 4.0% of patients in group A, in 10.0% of patients in group B, and in 31.4% of patients in group C (P < .0001 for group A vs B or A vs C). Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted hazard ratio, 0.47, 95% confidence interval, 0.25-0.91; P = .025), whereas smoking abstinence did not. CONCLUSIONS Multiple dysplastic lesions in the esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.
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Affiliation(s)
- Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Tetsuji Yokoyama
- Department of Health Promotion, National Institute of Public Health, Wako, Japan
| | - Tomonori Yano
- Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Japan
| | - Kazuhiro Kaneko
- Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yuichi Shimizu
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hisashi Doyama
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Takako Yoshii
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Kazuo Konishi
- Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Takenori Yamanouchi
- Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Japan
| | - Takashi Tsuda
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tai Omori
- Department of Endoscopy Center, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan
| | - Nozomu Kobayashi
- Department of Diagnostic Imaging, Tochigi Cancer Center, Utsunomiya, Japan
| | - Tadakazu Shimoda
- Division of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Atsushi Ochiai
- Division of Pathology, National Cancer Center Hospital and Hospital East, Tokyo, Japan
| | - Yusuke Amanuma
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shinya Ohashi
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tomonari Matsuda
- Research Center for Environmental Quality Management, Kyoto University, Otsu, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Yokoyama
- Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Kumamoto T, Sentani K, Oka S, Tanaka S, Yasui W. Clinicopathologic characteristics and management of minute esophageal lesions diagnosed by narrow-band imaging endoscopy. Endosc Int Open 2016; 4:E927-32. [PMID: 27652295 PMCID: PMC5025308 DOI: 10.1055/s-0042-110788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 06/13/2016] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Magnifying narrow-band imaging (NBI) endoscopy enables the diagnosis of minute esophageal neoplasia. We aimed to evaluate clinicopathological diagnosis of minute esophageal neoplasia by using magnifying NBI endoscopy and biopsy. PATIENTS AND METHODS In total, 309 patients (127 men and 182 women) with minute esophageal lesions of intrapapillary capillary loop (IPCL) type IV were enrolled. Of these patients, 249 underwent biopsy for histologic diagnosis and also for treatment. Of the 249 patients, 123 underwent follow-up with endoscopy. We analyzed the clinicopathologic characteristics and prognosis of these lesions after biopsy. RESULTS Of the 249 biopsied lesions, we histologically diagnosed 11 as high-grade intraepithelial neoplasia (HGIN), 41 as low-grade intraepithelial neoplasia (LGIN), and 197 as non-neoplasia (Non-N) including inflammation. Six of the 11 HGINs and 11 of the 41 LGINs showed slight elevation. Background coloration was observed in 9 of 11 HGINs, 34 of 41 LGINs, and 33 of 197 Non-Ns. Of the 249 biopsied lesions, 147 were microscopically measurable. The average diameter was 1.4 mm for HGINs and 0.8 mm for LGINs. Of the 123 patients who underwent post-biopsy follow-up, 93 (76 %) showed no lesions at the biopsied sites during the NBI examinations and were suspected to have undergone complete resection by biopsy. CONCLUSIONS Biopsy was useful for diagnosis and treatment of minute esophageal lesions, diagnosed as IPCL type IV by magnifying NBI endoscopy.
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Affiliation(s)
- Takashi Kumamoto
- Kumamoto Gastrointestinal Clinic, Hiroshima, Japan,Corresponding author Takashi Kumamoto Kumamoto Gastrointestinal Clinic1-5-2 OtemachiNaka-kuHiroshima 730-0051Japan+81-82-544-0606+81-82-544-0377
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Shiro Oka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Wataru Yasui
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent Advances From Basic and Clinical Studies of Esophageal Squamous Cell Carcinoma. Gastroenterology 2015; 149:1700-15. [PMID: 26376349 DOI: 10.1053/j.gastro.2015.08.054] [Citation(s) in RCA: 401] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 08/17/2015] [Accepted: 08/17/2015] [Indexed: 02/08/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is highly prevalent in Asia. Alcohol and its metabolite, acetaldehyde, are considered definite carcinogens for the esophagus. Polymorphisms in the aldehyde dehydrogenase 2 gene, which encodes an enzyme that eliminates acetaldehyde, have been associated with esophageal carcinogenesis. Studies of the mutagenic and carcinogenic effects of acetaldehyde support this observation. Several recent large-scale comprehensive analyses of the genomic alterations in ESCC have shown a high frequency of mutations in genes such as TP53 and others that regulate the cell cycle or cell differentiation. Moreover, whole genome and whole exome sequencing studies have frequently detected somatic mutations, such as G:C→A:T transitions or G:C→C:G transversions, in ESCC tissues. Genomic instability, caused by abnormalities in the Fanconi anemia DNA repair pathway, is also considered a pathogenic mechanism of ESCC. Advances in diagnostic techniques such as magnifying endoscopy with narrow band imaging or positron emission tomography have increased the accuracy of diagnosis of ESCC. Updated guidelines from the National Comprehensive Cancer Network standardize the practice for the diagnosis and treatment of esophageal cancer. Patients with ESCC are treated endoscopically or with surgery, chemotherapy, or radiotherapy, based on tumor stage. Minimally invasive treatments help improve the quality of life of patients who undergo such treatments. We review recent developments in the diagnosis and treatment of ESCC and advances gained from basic and clinical research.
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Affiliation(s)
- Shinya Ohashi
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto, Japan
| | - Shin'ichi Miyamoto
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Osamu Kikuchi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tomoyuki Goto
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yusuke Amanuma
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto, Japan.
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Wang WL, Wang YC, Chang CY, Lo JL, Kuo YH, Hwang TZ, Wang CC, Mo LR, Lin JT, Lee CT. Human papillomavirus infection on initiating synchronous esophageal neoplasia in patients with head and neck cancer. Laryngoscope 2015; 126:1097-102. [PMID: 27107411 DOI: 10.1002/lary.25728] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Revised: 09/02/2015] [Accepted: 09/15/2015] [Indexed: 12/30/2022]
Abstract
OBJECTIVES/HYPOTHESIS Human papillomavirus (HPV) is a risk factor for head and neck squamous cell carcinoma (HNSCC) as well as esophageal squamous cell carcinoma (ESCC). We aimed to investigate whether HPV infection underlies the field cancerization phenomenon over upper aerodigestive tract to develop synchronous multiple cancers. STUDY DESIGN A case control study. METHODS The presence and subtype of HPV-DNA sequence in cancers were examined by polymerase chain reaction and sequencing in a prospective cohort with 100 HNSCCs, 50 of which had synchronous ESCCs. The clinicopathologic characteristics were further analyzed according to the presence of HPV. RESULTS Twelve patients were HPV-positive, of which 11 were positive for HPV-16. The prevalence of HPV infection were not different between the synchronous and HNSCC alone groups (P = 0.357). Testing for HPV in paired HNSCC and ESCC tissues from the same patient revealed that none were concomitantly HPV-positive. Multivariate logistic regression showed drinking alcohol (odds ratio [OR], 18.75; P = 0.030), alcohol flushing (OR, 2.53; P = 0.041), and body mass index (OR, 0.77; P = 0.001) but not HPV infection were independent risk factors for synchronous phenotype. The patients with synchronous ESCCs had significantly poorer survival than those with HNSCC alone (5-year overall survival: 30% vs. 70%; log-rank P < 0.001). However, patients with HPV-positive HNSCC tend to have favorable outcome than those with HPV-negative HNSCC. CONCLUSIONS HPV infection plays little role in field cancerization phenomenon to initiate synchronous SCC. The synchronous HNSCC and ESCC from the same patients had no clonal relationship. Routine endoscopic examination of the esophagus should be recommended for patients with risk factors identified. LEVELS OF EVIDENCE NA. Laryngoscope, 126:1097-1102, 2016.
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Affiliation(s)
- Wen-Lun Wang
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung
| | - Yu-Chi Wang
- Department of Biological Science and Technology, E-Da Hospital/I-Shou University, Kaohsiung
| | - Chi-Yang Chang
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung
| | - Jo-Lin Lo
- Department of Oncology, E-Da Hospital/I-Shou University, Kaohsiung
| | - Yao-Hung Kuo
- Department of Radiation Oncology, E-Da Hospital/I-Shou University, Kaohsiung
| | - Tzer-Zen Hwang
- Department of Otolaryngology, E-Da Hospital/I-Shou University, Kaohsiung
| | - Chih-Chun Wang
- Department of Otolaryngology, E-Da Hospital/I-Shou University, Kaohsiung
| | - Lein-Ray Mo
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung
| | - Jaw-Town Lin
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung.,Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Ching-Tai Lee
- Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung
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Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium. Sci Rep 2015; 5:14142. [PMID: 26374466 PMCID: PMC4570974 DOI: 10.1038/srep14142] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 08/11/2015] [Indexed: 12/14/2022] Open
Abstract
Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N2-ethylidene-2′-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N2-ethylidene-2′-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N2-ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.
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Yamasaki Y, Takenaka R, Hori K, Takemoto K, Kawano S, Kawahara Y, Okada H, Fujiki S, Yamamoto K. Tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening. World J Gastroenterol 2015; 21:2793-2799. [PMID: 25759551 PMCID: PMC4351233 DOI: 10.3748/wjg.v21.i9.2793] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 11/21/2014] [Accepted: 12/22/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening with that of lugol chromoendoscopy.
METHODS: We prospectively enrolled and analyzed 51 patients who were at high risk for esophageal cancer. All patients were divided into two groups: a magnifying narrow band imaging group, and a lugol chromoendoscopy group, for comparison of adverse symptoms. Esophageal cancer screening was performed on withdrawal of the endoscope. The primary endpoint was a score on a visual analogue scale for heartburn after the examination. The secondary endpoints were scale scores for retrosternal pain and dyspnea after the examinations, change in vital signs, total procedure time, and esophageal observation time.
RESULTS: The scores for heartburn and retrosternal pain in the magnifying narrow band imaging group were significantly better than those in the lugol chromoendoscopy group (P = 0.004, 0.024, respectively, ANOVA for repeated measures). The increase in heart rate after the procedure was significantly greater in the lugol chromoendoscopy group. There was no significant difference between the two groups with respect to other vital sign. The total procedure time and esophageal observation time in the magnifying narrow band imaging group were significantly shorter than those in the lugol chromoendoscopy group (450 ± 116 vs 565 ± 174, P = 0.004, 44 ± 26 vs 151 ± 72, P < 0.001, respectively).
CONCLUSION: Magnifying narrow band imaging endoscopy reduced the adverse symptoms compared with lugol chromoendoscopy. Narrow band imaging endoscopy is useful and suitable for esophageal cancer screening periodically.
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Association between ADH1B and ADH1C polymorphisms and the risk of head and neck squamous cell carcinoma. Tumour Biol 2015; 36:4387-96. [PMID: 25874489 DOI: 10.1007/s13277-015-3078-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 01/08/2015] [Indexed: 02/05/2023] Open
Abstract
Alcohol consumption is one of the major risk factors for head and neck squamous cell carcinoma (HNSCC), and the alcohol dehydrogenase (ADH) family proteins are key enzymes in ethanol metabolism. We examined the associations between single nucleotide polymorphisms (SNPs) of ADH1B and ADH1C and the risk of HNSCC. We analyzed six SNPS of ADH1B, namely -992C > G, -957C > A, +3170A>G, +3377G>T, +3491G>A, and +13543A>G, and five SNPs of ADH1C, namely -1064C>T, -325G>C, +5702A>G, +7462T>C, and +13044A>G, in 260 Korean HNSCC patients and 330 controls, using single base extension and the TaqMan assay. The odds ratios (ORs) and 95 % confidence intervals (95 % CIs) of the CG and GG genotypes of ADH1B -992C>G, the AA genotype of -957C>A, the GG genotype of +3170A>G, the GA genotype of +3491G>A, and +13543A>G were 0.51 (0.32-0.82), 0.63 (0.42-0.94), 1.84 (1.13-2.99), 1.77 (1.15-2.73), 2.34 (1.44-3.79), and 2.21 (1.23-3.95), respectively. The ORs of ADH1C +13044A>G were 1.94 (1.01-3.71) and 1.97 (1.05-3.71) in the dominant and co-dominant models, respectively. The ORs of the GC genotype of ADH1C -325G>C and the AG genotype of +5702A>G were 2.52 (1.51-4.21) and 2.43 (1.36-4.32), respectively. ADH1B +3170A>G and ADH1C +13044A>G were in strong linkage disequilibrium with the other SNPs of ADH1B and ADH1C, respectively. There were gene-environment interactions between ADH1B +3170A>G and ADH1C +13044A>G and alcohol consumption and smoking. ADH1B +3170A>G and ADH1C +13044A>G SNPs are associated with an increased risk of HNSCC, and they could be used as biomarkers for the high-risk group of HNSCC in Koreans.
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Zhong H, Yin H. Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biol 2014; 4:193-9. [PMID: 25598486 PMCID: PMC4803793 DOI: 10.1016/j.redox.2014.12.011] [Citation(s) in RCA: 363] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 12/17/2014] [Indexed: 12/20/2022] Open
Abstract
Oxidative stress-induced lipid peroxidation has been associated with human physiology and diseases including cancer. Overwhelming data suggest that reactive lipid mediators generated from this process, such as 4-hydroxynonenal (4-HNE), are biomarkers for oxidative stress and important players for mediating a number of signaling pathways. The biological effects of 4-HNE are primarily due to covalent modification of important biomolecules including proteins, DNA, and phospholipids containing amino group. In this review, we summarize recent progress on the role of 4-HNE in pathogenesis of cancer and focus on the involvement of mitochondria: generation of 4-HNE from oxidation of mitochondria-specific phospholipid cardiolipin; covalent modification of mitochondrial proteins, lipids, and DNA; potential therapeutic strategies for targeting mitochondrial ROS generation, lipid peroxidation, and 4-HNE.
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Affiliation(s)
- Huiqin Zhong
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences (INS), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China; University of the Chinese Academy of Sciences, CAS, Beijing, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China
| | - Huiyong Yin
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences (INS), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China; University of the Chinese Academy of Sciences, CAS, Beijing, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
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Eriksson CJP. Genetic–Epidemiological Evidence for the Role of Acetaldehyde in Cancers Related to Alcohol Drinking. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2014; 815:41-58. [DOI: 10.1007/978-3-319-09614-8_3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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