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Gao SG, Qi ZP, Qi YJ, Hou YY, Liu YW, Li MX, Li B, Sun D, Shi Q, Cai SL, Zhou PH, Zhong YS. Porphyromonas gingivalis predicts local recurrence after endoscopic submucosal dissection of early esophageal squamous cell carcinoma or precancerous lesion. BMC Cancer 2023; 23:43. [PMID: 36635649 PMCID: PMC9837911 DOI: 10.1186/s12885-022-10469-8] [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] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 12/21/2022] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Porphyromonas gingivalis plays an oncogenic role in development and progression of esophageal squamous cell carcinoma (ESCC). However, the impact of P. gingivalis on local recurrence of early ESCC or precancerous lesion after ESD treatment remains unknown. The present study aimed to evaluate the impact of P. gingivalis on local recurrence after ESD treatment of early ESCC or high-grade dysplasia (HGD). METHODS The amount of P. gingivalis was assessed by immunohistochemistry in 205 patients with early ESCC or HGD. Univariate and multivariate Cox regression analyses were performed to determine the effect of P. gingivalis on local recurrence. Propensity score matching analysis was performed to reduce the imbalance of baseline characteristics. A nomogram integrating significant prognostic factors was built for local recurrence prediction. RESULTS The amount of P. gingivalis increased significantly in neoplasms that invaded up to muscularis mucosa and submucosa compared with lesions confined to epithelium or lamina propria. Overabundance of P. gingivalis was positively associated with invasion depth, post-ESD stricture and local recurrence. Univariate and multivariate Cox regression analyses revealed that P. gingivalis, longitudinal length of lesion and lymphovascular invasion were independent predictors for post-ESD recurrence. A nomogram comprising P. gingivalis, lymphovascular involvement, and lesion length performed well for prediction of post-ESD local recurrence with the concordance indices of 0.72 (95%CI, 0.62 to 0.80), 0.72 (95%CI, 0.63 to 0.80), and 0.74 (95%CI, 0.65 to 0.83) in the validation cohort, the entire cohort, and the subcohort after PSM, respectively. CONCLUSION P. gingivalis overabundance is a risk factor and a potential predictor for local recurrence of early ESCC or HGD after ESD treatment. Thus, clearance of P. gingivalis represents an attractive strategy for prognosis improvement and for prevention of ESCC.
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Affiliation(s)
- She-Gan Gao
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, 471003, Luoyang, China.
| | - Zhi-Peng Qi
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, 471003, Luoyang, China
- Endoscopy Center, Zhongshan Hospital of Fudan University, 200032, Shanghai, China
- Endoscopy Research Institute of Fudan University, 200032, Shanghai, China
| | - Yi-Jun Qi
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, 471003, Luoyang, China
| | - Ying-Yong Hou
- Department of Pathology, Zhongshan Hospital of Fudan University, 200032, Shanghai, China
| | - Yi-Wen Liu
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, 471003, Luoyang, China
| | - Meng-Xiang Li
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, 471003, Luoyang, China
| | - Bing Li
- Endoscopy Center, Zhongshan Hospital of Fudan University, 200032, Shanghai, China
- Endoscopy Research Institute of Fudan University, 200032, Shanghai, China
| | - Di Sun
- Endoscopy Center, Zhongshan Hospital of Fudan University, 200032, Shanghai, China
- Endoscopy Research Institute of Fudan University, 200032, Shanghai, China
| | - Qiang Shi
- Endoscopy Center, Zhongshan Hospital of Fudan University, 200032, Shanghai, China
- Endoscopy Research Institute of Fudan University, 200032, Shanghai, China
| | - Shi-Lun Cai
- Endoscopy Center, Zhongshan Hospital of Fudan University, 200032, Shanghai, China
- Endoscopy Research Institute of Fudan University, 200032, Shanghai, China
| | - Ping-Hong Zhou
- Endoscopy Center, Zhongshan Hospital of Fudan University, 200032, Shanghai, China
- Endoscopy Research Institute of Fudan University, 200032, Shanghai, China
| | - Yun-Shi Zhong
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, 471003, Luoyang, China.
- Endoscopy Center, Zhongshan Hospital of Fudan University, 200032, Shanghai, China.
- Endoscopy Research Institute of Fudan University, 200032, Shanghai, China.
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Betancourt-Cuellar SL, Benveniste MFK, Palacio DP, Hofstetter WL. Esophageal Cancer: Tumor-Node-Metastasis Staging. Radiol Clin North Am 2021; 59:219-229. [PMID: 33551083 DOI: 10.1016/j.rcl.2020.11.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Esophageal cancer is an uncommon malignancy that ranks sixth in terms of mortality worldwide. Squamous cell carcinoma is the predominant histologic subtype worldwide whereas adenocarcinoma represents the majority of cases in North America, Australia, and Europe. Esophageal cancer is staged using the American Joint Committee on Cancer and the International Union for Cancer Control TNM system and has separate classifications for the clinical, pathologic, and postneoadjuvant pathologic stage groups. The determination of clinical TNM is based on complementary imaging modalities, including esophagogastroduodenoscopy/endoscopic ultrasound; endoscopic ultrasound-fine-needle aspiration; computed tomography of the chest, abdomen, and pelvis; and fluorodeoxyglucose PET/computed tomography.
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Affiliation(s)
- Sonia L Betancourt-Cuellar
- Thoracic Imaging Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1478, Houston, TX 77030-4009, USA.
| | - Marcelo F K Benveniste
- Thoracic Imaging Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1478, Houston, TX 77030-4009, USA
| | - Diana P Palacio
- Department of Medical Imaging, The University of Arizona - Banner Medical Center, 1501 North Campbell Avenue, PO BOX 245067, Tucson, AZ 85724, USA
| | - Wayne L Hofstetter
- Cardiothoracic Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1489, Houston, TX 77030-4009, USA
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Krill T, Baliss M, Roark R, Sydor M, Samuel R, Zaibaq J, Guturu P, Parupudi S. Accuracy of endoscopic ultrasound in esophageal cancer staging. J Thorac Dis 2019; 11:S1602-S1609. [PMID: 31489227 DOI: 10.21037/jtd.2019.06.50] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Since its advent in the 1980s endoscopic ultrasound (EUS) has played an important role in the diagnosis, staging, and therapeutic management of various gastrointestinal malignancies. EUS has emerged as a vital tool in the evaluation of esophageal cancer as it provides a detailed view of the layers of the esophageal wall and surrounding tissues. This permits determination of tumor invasion depth and local lymph node metastases. It is the most sensitive and specific method available for locoregional staging of esophageal cancer. The information obtained via EUS is vital in determining the appropriate diagnosis, prognosis, and treatment options. Thus, this article aims to present a review of the accuracy and utilization of EUS in the staging of esophageal cancer.
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Affiliation(s)
- Timothy Krill
- Department of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX, USA
| | - Michelle Baliss
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Russel Roark
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Michael Sydor
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Ronald Samuel
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Jenine Zaibaq
- Department of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX, USA
| | - Praveen Guturu
- Department of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX, USA
| | - Sreeram Parupudi
- Department of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX, USA
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Vohlonen I, Härkönen M, Malila N, Pukkala E, Sipponen P, Koistinen V, Hakama M. Challenges in evaluation of screening for gastric cancer among men based on nonrandomized design. Acta Oncol 2017; 56:917-922. [PMID: 28514928 DOI: 10.1080/0284186x.2016.1278304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Objective was to quantify biases in screening for gastric cancer when comparing attenders to nonattenders using serum pepsinogen I (SPGI) level as primary test. METHODS In mid 1990s, all men aged 51-65 years from two Finnish cities were invited to SPGI screening. Mortality and premature mortality in attenders were compared to nonattenders. Efficacy of screening was studied by 15 years' follow-up of standardized mortality ratio (SMR) and potential years of life lost (PYLL) due to gastric cancer. Bias due to selective attendance was quantified using corrective coefficients based on total cancer incidence and mortality, and gastric cancer-specific incidence and mortality for total population and nonattenders. RESULTS In 1994-1996, men aged 51-65 years (16,872) were invited to SPGI assay and 12,175 men (72%) attended. SPGI was 25 microg/l or less in 610 (5%) men, indicating severe atrophic gastritis (AG). Post-screening gastroscopy was performed to 435 men with low SPGI. Of these, 168 men were referred for treatment due to abnormal focal lesions. Attributable proportions in reductions of SMR and PYLL from gastric cancer due to screening were 59% and 67%. After correcting for selective participation, attributable proportions were reduced to 23% and 39%. CONCLUSIONS Biomarker screening by low SPGI among middle-aged men followed by upper gastrointestinal endoscopy decreased long-term and premature mortality due to gastric cancer. However, in spite of methodological corrections done, the results do not justify any firm conclusions or recommend general screening programs. Randomized trials are warranted for this purpose.
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Affiliation(s)
- Ilkka Vohlonen
- Department of Public Health, Health Policy, University of Eastern Finland, Kuopio, Finland
| | - Matti Härkönen
- Department of Clinical Chemistry, Clinical Chemistry, University of Helsinki, Helsinki, Finland
| | - Nea Malila
- Cancer Epidemiology, Finnish Cancer Registry, Helsinki, Finland
- School of Health Sciences, University of Tampere, Tampere, Finland
| | - Eero Pukkala
- Epidemiology, Finnish Cancer Registry, Helsinki, Finland
- School of Health Sciences, University of Tampere, Tampere, Finland
| | | | - Veli Koistinen
- Department of Biostatistics, Finnish Consulting Group, Helsinki, Finland
| | - Matti Hakama
- Department of Epidemiology, Finnish Cancer Registry, Helsinki, Finland
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Jiang D, Li X, Wang H, Xu C, Li X, Sujie A, Zeng H, Hou Y, Zhong Y. A retrospective study of endoscopic resection for 368 patients with early esophageal squamous cell carcinoma or precancerous lesions. Surg Endosc 2016; 31:2122-2130. [PMID: 27837320 DOI: 10.1007/s00464-016-5208-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 08/20/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND To retrospectively investigate the clinicopathological features and prognosis of early esophageal squamous cell neoplasm (ESCN) treated with endoscopic resection (ER), especially, to compare the prognosis in patients with sm2 cancer and non-sm2 cancer. METHODS From 2007 to 2013, 368 patients were included in our analysis. RESULTS The patients were 252 (68.5 %) men and 116 (31.5 %) women with a median age of 61 (range 16-84 years) years. Hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia, m1, m2, m3, sm1, and sm2 were diagnosed in 47 (12.8 %), 27 (7.3 %), 34 (9.2 %), 61 (16.6 %), 54 (14.7 %), 38 (10.3 %), 63 (17.1 %), 12 (3.3 %), and 32 (8.7 %) cases. The mean (range) follow-up time was 29 (0-84) months. The cumulative overall 1-, 3-, and 5-year metachronous esophageal lesion rates were 4.1, 12.9, and 32.6 %. The incidence of lymph node or distant metastasis was 1.54 % in m3, 6.25 % in sm2, and 0 in other subgroups. The overall 1-, 3-, and 5-year survival rates were 99.5, 97.3, and 87.5 %. There was significant difference between sm2 and non-sm2 patients in metastatic rate (P = 0.021); however, no difference existed between m3 patients and sm2 patients (P = 0.252). The difference of metachronous esophageal lesion (P = 0.401) and survival (P = 0.634) between sm2 and non-sm2 patients was not obvious. CONCLUSIONS Our study showed that ER was an effective and relatively safe treatment for superficial ESCN. ER is still appropriate in select sm2 patients. To monitor the second primary cancer in sm2 is necessary during the follow-up.
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Affiliation(s)
- Dongxian Jiang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Xuquan Li
- Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Haixing Wang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Chen Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Xiaojing Li
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Akesu Sujie
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Haiying Zeng
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China
| | - Yingyong Hou
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
| | - Yunshi Zhong
- Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
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Espinel J, Pinedo E, Ojeda V, Rio MGD. Multiband mucosectomy for advanced dysplastic lesions in the upper digestive tract. World J Gastrointest Endosc 2015; 7:370-380. [PMID: 25901216 PMCID: PMC4400626 DOI: 10.4253/wjge.v7.i4.370] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Revised: 12/20/2014] [Accepted: 01/19/2015] [Indexed: 02/05/2023] Open
Abstract
Endoscopic resection (ER) is at present an accepted treatment for superficial gastrointestinal neoplasia. ER provides similar efficacy to surgery; however, it is minimally invasive and less expensive. Endoscopic mucosal resection (EMR) is superior to biopsy for diagnosing advanced dysplasia and can change the diagnostic grade and the management. Several EMR techniques have been described that are alternatively used dependent upon the endoscopist personal experience, the anatomic conditions and the endoscopic appearance of the lesion to be resected. The literature suggests that EMR offers comparable outcomes to surgery for selected indications. EMR techniques using a cap fitted endoscope and EMR using a ligation device [multiband mucosectomy (MBM)] are the most frequently use. MBM technique does not require submucosal injection as with the endoscopic resection-cap technique, multiple resections can be performed with the same snare, pre-looping the endoscopic resection-snare in the ridge of the cap is not necessary, MBM does not require withdrawal of the endoscope between resections and up to six consecutive resections can be performed. This reduces the time and cost required for the procedure, while also reducing patient discomfort. Despite the increasing popularity of MBM, data on the safety and efficacy of this technique in upper gastrointestinal lesions with advanced dysplasia, defined as those lesions that have high-grade dysplasia or early cancer, is limited.
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Huntington JT, Walker JP, Meara MP, Hazey JW, Melvin WS, Perry KA. Endoscopic mucosal resection for staging and treatment of early esophageal carcinoma: a single institution experience. Surg Endosc 2014; 29:2121-5. [PMID: 25472745 DOI: 10.1007/s00464-014-3962-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 10/25/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Endoscopic mucosal resection (EMR) has emerged for evaluation and treatment of esophageal nodules. We report our initial experience with EMR for T staging and management of early esophageal cancer. METHODS We reviewed patients undergoing EMR for esophageal adenocarcinoma between 2008 and 2013. The primary outcome measure was needed for esophagectomy. Secondary outcomes included complete eradication of adenocarcinoma, recurrence or persistence of cancer, nodal status for those undergoing esophagectomy, and complications of endoscopic treatment. RESULTS During the study period, 24 patients underwent EMR demonstrating carcinoma, and a grossly margin negative endoscopic resection was achieved in all cases. Ten patients (42 %) had evidence of submucosal invasion and were referred for esophagectomy. Patients with margin negative EMR (n = 10, 42 %) or positive radial margins (n = 4, 16 %) underwent endoscopic surveillance and treatment with radiofrequency ablation or repeat EMR as needed. Thirteen patients (93 %) with intramucosal cancer (IMC) have been successfully managed with ongoing endoscopic surveillance and treatment with a median follow-up of 15.5 months. One patient underwent esophagectomy due to recurrent IMC in the setting of long-segment multifocal high-grade dysplasia. There were no esophageal perforations, one patient developed a self-limited gastrointestinal hemorrhage following EMR, and one had an esophageal stricture following endoscopic management. CONCLUSIONS IMC can be successfully managed endoscopically and thus esophagectomy is avoided in a significant proportion of patients. Endoscopic management may be utilized in the setting of complete resection or radial margin involvement without evidence of submucosal invasion. Close endoscopic follow-up is of paramount importance even in those with negative margins, because recurrent disease may occur following EMR in these patients.
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Affiliation(s)
- Justin T Huntington
- Division of General and Gastrointestinal Surgery, The Ohio State University, Columbus, OH, 43210, USA,
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Zhou SS, Yan S, Chen WC, Shi DT, Fu T. Accuracy of endoscopic ultrasound in preoperative staging of early esophageal cancer: A Meta-analysis. Shijie Huaren Xiaohua Zazhi 2014; 22:988-999. [DOI: 10.11569/wcjd.v22.i7.988] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) in the preoperative staging of early esophageal cancer.
METHODS: We searched the Medline, PubMed, Web of Science, Embase, Cochrane Central Trials, Wanfang, CBM, CNKI and VIP databases for relevant studies published. Study selection, quality assessment and data extraction were performed by two reviewers independently. Meta-Disc (version1.4) software was used to perform the meta-analysis for sensitivity, specificity, positive likelihood ratio (LR), and negative LR. Pooling results were derived (by) using the fixed-effect model when significant heterogeneity was not present, and the random-effect model was applied otherwise. A summary receiver-operating characteristic (SROC) curve was constructed. Furthermore, to explore the potential sources of heterogeneity, we used meta-regression to estimate the effect of the characteristics of the studies on the diagnostic accuracy of EUS. In addition, the outliers were identified by the method described by Deville and a subgroup analysis was performed by excluding the outliers. We used Stata statistical software (version 10.0) to assess the publication bias using the Begg-Mazumdar indictor and Harbord-Egger indictor.
RESULTS: Twenty studies with a total of 1115 patients were included in this analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratio of EUS for T1m staging were 0.85 (95%CI: 0.83-0.88), 0.86 (95%CI: 0.83-0.89), 5.34 (95%CI: 3.67-7.76), and 0.21 (95%CI: 0.15-0.29), respectively. For stage T1sm, these results were 0.87 (95%CI: 0.84-0.90), 0.85 (95%CI: 0.82-0.88), 4.64 (95%CI: 3.47-6.22), and 0.18 (95%CI: 0.13-0.25). For stage N, these results were 0.71 (95%CI: 0.61-0.80), 0.78 (95%CI: 0.71-0.84), 2.93 (95%CI: 1.49-5.79), and 0.46 (95%CI: 0.18-1.22). The percent of area under the curve was 92.1% for both stage T1m and stage T1sm, and 80% for stage N. No significant publication bias was found with either the Begg-Mazumdar indictor (P = 0.216) or the Harbord-Egger indictor (P = 0. 412).
CONCLUSION: EUS has excellent sensitivity and specificity in diagnosing the T1 stage of early esophageal cancer. However, the frequency of EUS probe and the experience of the endosonographers can affect the diagnostic accuracy of EUS. EUS plays an important role in clinical selection of surgical approaches and treatments.
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Nasuno T, Mimaki S, Okamoto M, Esumi H, Tsuchihara K. Effect of a poly(ADP-ribose) polymerase-1 inhibitor against esophageal squamous cell carcinoma cell lines. Cancer Sci 2013; 105:202-10. [PMID: 24219164 PMCID: PMC4317825 DOI: 10.1111/cas.12322] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Revised: 11/05/2013] [Accepted: 11/11/2013] [Indexed: 12/25/2022] Open
Abstract
Effective molecular target drugs that improve therapeutic efficacy with fewer adverse effects for esophageal cancer are highly anticipated. Poly(ADP-ribose) polymerase (PARP) inhibitors have been proposed as low-toxicity agents to treat double strand break (DSB)-repair defective tumors. Several findings imply the potential relevance of DSB repair defects in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). We evaluated the effect of a PARP Inhibitor (AZD2281) on the TE-series ESCC cell lines. Of these eight cell lines, the clonogenic survival of one (TE-6) was reduced by AZD2281 to the level of DSB repair-defective Capan-1 and HCC1937 cells. AZD2281-induced DNA damage was implied by increases in γ-H2AX and cell cycle arrest at G2/M phase. The impairment of DSB repair in TE-6 cells was suggested by a sustained increase in γ-H2AX levels and the tail moment calculated from a neutral comet assay after X-ray irradiation. Because the formation of nuclear DSB repair protein foci was impaired in TE-6 cells, whole-exome sequencing of these cells was performed to explore the gene mutations that might be responsible. A novel mutation in RNF8, an E3 ligase targeting γ-H2AX was identified. Consistent with this, polyubiquitination of γ-H2AX after irradiation was impaired in TE-6 cells. Thus, AZD2281 induced growth retardation of the DSB repair-impaired TE-6 cells. Interestingly, a strong correlation between basal expression levels of γ-H2AX and sensitivity to AZD2281was observed in the TE-series cells (R2 = 0.5345). Because the assessment of basal DSB status could serve as a biomarker for selecting PARP inhibitor-tractable tumors, further investigation is warranted.
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Affiliation(s)
- Tomomitsu Nasuno
- Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan; Department of Otorhinolaryngology, University of Kitasato Hospital, Minami-ku, Sagamihara, Kanagawa, Japan
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Qumseya BJ, Wolfsen C, Wang Y, Othman M, Raimondo M, Bouras E, Wolfsen H, Wallace MB, Woodward T. Factors associated with increased bleeding post-endoscopic mucosal resection. J Dig Dis 2013; 14:140-6. [PMID: 23134152 DOI: 10.1111/1751-2980.12002] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Our aim was to identify patient and procedure characteristics that correlate with increased likelihood of bleeding during and after endoscopic mucosal resection (EMR), and thus anticipate the need for preventative therapy. METHODS This was a retrospective, observational, descriptive study using a prospective EMR database, performed in a tertiary-care center. A total of 935 EMR of various locations within the gastrointestinal tract were collected. The main outcome measurement was early bleeding (occurring during the procedure) and delayed bleeding (occurring after the completion of the procedure and up to 30 days after). RESULTS Early bleeding occurred in 5.3% (50/935) of the procedures. In multivariate logistic regression analysis, esophageal EMR (OR 2.5, 95% CI 1.2-5, P = 0.0009) and increase in lesion size (OR 1.24, 95% CI 1.1-1.5, P = 0.003) were both associated with higher odds of early bleeding in EMR when controlling for age, gender and non-steroidal anti-inflammatory drugs (NSAIDs)/clopidogrel use. Delayed bleeding occurred after 3.1% (n = 29) of the procedures. Of these, 86.2% (25/29) required hospital admission and endoscopic intervention to confirm and/or treat bleeding site. In multivariate logistic regression analysis, increased lesion size (OR 1.3, 95% CI 1.1-1.5, P = 0.004) was associated with higher incidence of delayed bleeding post-EMR. CONCLUSIONS In experienced hands bleeding during and after EMR appears to be uncommon. Larger lesions are at increased risk of early and delayed bleeding.
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Affiliation(s)
- Bashar J Qumseya
- Department of Gastroenterology & Hepatology, Mayo Clinic, Jacksonville, FL 32224, USA
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Evolving changes in the management of early oesophageal adenocarcinoma in a tertiary centre. Ir J Med Sci 2012; 182:363-9. [PMID: 23242575 DOI: 10.1007/s11845-012-0890-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2012] [Accepted: 11/28/2012] [Indexed: 01/04/2023]
Abstract
OBJECTIVES Series from high volume oesophageal centres highlight an increasing prevalence of early malignant (EM) lesions. The advent of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) offer alternatives to traditional surgery. The evolution of this pattern of care in a high volume centre is analysed. METHODS Data were collected from a prospectively maintained database. 96 patients were treated with an EM lesion from 2000 to 2011. Surgery was the standard approach during the initial period (2000-2006). In 2007, with the introduction of EMR±RFA to our Centre, a rising trend toward definitive endoscopic treatment was seen. This study details the selection of cases into treatment groups and their outcomes. RESULTS From 2000 to 2006, 23 patients were treated with EM lesions, 96% by surgery. Seventy-three were treated from 2007 to 2011, 55% surgically and 45% by EMR±RFA. In the entire experience, there was one death from surgery and morbidity was higher in the surgery group compared with EMR±RFA (p<0.001). Three surgical patients (4.8%) relapsed with HGD or cancer, and one patient with T1N1 disease died of disease recurrence. At a median of 13 months, EMR±RFA offered 100% disease control, 72% had no endoscopic or histological evidence of Barrett's oesophagus and one patient represented with low grade dysplasia. CONCLUSIONS This study highlights the changing pattern of care in the management of early oesophageal cancer. EMR±RFA appears an acceptable alternative to surgery in carefully selected cases. However, long-term outcome analysis using these methods is required and close interdisciplinary collaboration of specialists in gastroenterology, surgery, pathology and radiology is mandatory to achieve optimum outcomes.
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Endoscopic mucosal resection of a solitary metastatic tumor in the stomach: a case report. Surg Laparosc Endosc Percutan Tech 2012; 22:e132-4. [PMID: 22678333 DOI: 10.1097/sle.0b013e318247d13c] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Endoscopic mucosal resection (EMR) is increasingly being utilized in the management of early gastric cancer. Metastatic cancer of the stomach is uncommon. We report a case of solitary gastric metastasis from renal cell carcinoma (RCC) that was successfully excised with EMR. A 71-year-old man presented with iron deficiency anemia, he had undergone a radical nephrectomy for RCC 3 years previously. Upper gastrointestinal endoscopy revealed a malignant-appearing 10 × 12 mm polyp in the stomach. Histopathology of the biopsy revealed that it was a metastasis from RCC, confirmed by immunohistochemistry with Vimentin and CAM 5.2 positivity. Computed tomography and bone scanning revealed no other metastases. Simultaneous laparoscopy and upper gastrointestinal endoscopy revealed that the lesion was localized to the gastric mucosa. EMR of the tumor en bloc was performed successfully. Histology confirmed a complete excision. He had an uneventful postoperative course and is well 15 months after surgery, without any tumor recurrence.
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Thosani N, Singh H, Kapadia A, Ochi N, Lee JH, Ajani J, Swisher SG, Hofstetter WL, Guha S, Bhutani MS. Diagnostic accuracy of EUS in differentiating mucosal versus submucosal invasion of superficial esophageal cancers: a systematic review and meta-analysis. Gastrointest Endosc 2012; 75:242-253. [PMID: 22115605 DOI: 10.1016/j.gie.2011.09.016] [Citation(s) in RCA: 162] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2010] [Accepted: 09/06/2010] [Indexed: 02/08/2023]
Abstract
BACKGROUND The prognosis of esophageal cancer (EC) depends on the depth of tumor invasion and lymph node metastasis. EC limited to the mucosa (T1a) can be treated effectively with minimally invasive endoscopic therapy, whereas submucosal (T1b) EC carries relatively high risk of lymph node metastasis and requires surgical resection. OBJECTIVE To determine the diagnostic accuracy of EUS in differentiating T1a EC from T1b EC. DESIGN We performed a comprehensive search of MEDLINE, SCOPUS, Cochrane, and CINAHL Plus databases to identify studies in which results of EUS-based staging of EC were compared with the results of histopathology of EMR or surgically resected esophageal lesions. DerSimonian-Laird random-effects model was used to estimate the pooled sensitivity, specificity, and likelihood ratio, and a summary receiver operating characteristic (SROC) curve was created. SETTING Meta-analysis of 19 international studies. PATIENTS Total of 1019 patients with superficial EC (SEC). INTERVENTIONS EUS and EMR or surgical resection of SEC. MAIN OUTCOME MEASUREMENTS Sensitivity and specificity of EUS in accurately staging SEC. RESULTS The pooled sensitivity, specificity, and positive and negative likelihood ratio of EUS for T1a staging were 0.85 (95% CI, 0.82-0.88), 0.87 (95% CI, 0.84-0.90), 6.62 (95% CI, 3.61-12.12), and 0.20 (95% CI, 0.14-0.30), respectively. For T1b staging, these results were 0.86 (95% CI, 0.82-0.89), 0.86 (95% CI, 0.83-0.89), 5.13 (95% CI, 3.36-7.82), and 0.17 (95% CI, 0.09-0.30), respectively. The area under the curve was at least 0.93 for both mucosal and submucosal lesions. LIMITATIONS Heterogeneity was present among the studies. CONCLUSION Overall EUS has good accuracy (area under the curve ≥0.93) in staging SECs. Heterogeneity among the included studies suggests that multiple factors including the location and type of lesion, method and frequency of EUS probe, and the experience of the endosonographer can affect the diagnostic accuracy of EUS.
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Affiliation(s)
- Nirav Thosani
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas Medical School, Houston, Texas 77030, USA
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Schurr MO, Baur F, Ho CN, Anhoeck G, Kratt T, Gottwald T. Endoluminal full-thickness resection of GI lesions: a new device and technique. MINIM INVASIV THER 2011; 20:189-92. [PMID: 21574825 DOI: 10.3109/13645706.2011.582119] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Full-thickness resection techniques are of growing interest in the field of endoscopic removal of tumors or their precursors in the digestive tract. A new dedicated full-thickness resection device has been developed based on the combination of the OTSC clip, an enlarged resection cap and an integrated snare. The device prototype allows combined resection of all gastrointestinal organ wall layers in one maneuver, up to a size of 3 x 3 cm. The device has been pre-clinically tested to demonstrate feasibility of full-thickness resection in the colon. Two clinical cases have been performed successfully to date.
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