esophageal cancer
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Etiology
- squamous cell carcinoma
- most cases can be attributed to smoking or excess alcohol or both
- other risk factors:
- Plummer Vinson syndrome
- tylosis
- achalasia
- lye stricture
- human papilloma virus
- high fat, low protein, & low calorie diets increase risk
- nitrosamines (nitrates, nitrites) may be common etiology
- fungal toxins in pickled vegetables
- radiation-induced stricture
- zinc-deficiency may be risk
- hot or burning hot tea daily + smoking &/or drinking (see Camellia sinensis)[11]
- adenocarcinoma risk factors
- Barrett's esophagus (BE) & risk factors for BE
- gastroesophageal reflux
- smoking
- central obesity
- Causasian race
- age > 50 years
Epidemiology
- estimated 14,55 cases/year (2006)
- 7th leading cause of death from cancer in U.S.[3]
- 2.7 times more common in men than women
- adenocarcinoma 50%
- more frequent in US than squamous cell carcinoma with greatest frequency in males age 40-50
- more common in whites
- male/female ratio 7:1, black/white ratio 1:4
- squamous cell carcinoma 50%
- incidence increased with age & peaks in 7th decade
- more common in blacks
- most prominant histologic type world-wide
- male/female ratio 3:1, black/white ratio 6:1
- incidence 20-30 times higher in China than US
Pathology
- adenocarcinoma
- distal 1/3 of esophagus is most common site
- incidence of adenocarcinoma involving gastroesophageal (GE)-junction is increasing
- generally occurs on a background of Barrett's esophagus
- squamous cell carcinoma
- most often in proximal 2/3 of esophagus
- 10% may have malignant neoplasms of the oral cavity, pharynx, larynx or lung
- other types:
- metastatic spread
- regional lymph nodes
- lungs
- liver
- bone
- adrenal glands
- diaphragm
- adenocarcinoma may metastasize to brain
Genetics
- abnormal transcripts of FHIT found in ~50%
- downregulation of NMES1, DEC1
- upregulation of RABGAP1L (SCC), TNFRSF6B
- defects in DLEC1 are a cause of esophageal cancer
- DLEC1 silencing due to promoter methylation & aberrant transcription are implicated in the development ofesophageal cancer
- other implicated genes
Clinical manifestations
- progressive solid food dysphagia is the most common presenting symptom[3]
- dysphagia is not noted until esophageal lumen is narrowed to 1/2 to 1/3 of its normal diameter because of its elasticity
- weight loss is common
- cough is suggestive of local extension into the trachea with tracheal esophageal fistula
- pain may radiate to back
- hoarseness may be a sign of recurrent laryngeal nerve involvement
- metastatic disease may result in:
- pleural effusion
- ascites
- bone involvement may result in pain &/or hypercalcemia
Laboratory
- serum chemistries
- mismatch repair
- HER2/neu (ERBB2) in tissue
- trastuzumab is indicated for HER2-positive tumors
Diagnostic procedures
- endoscopy for visualization & esophageal biopsy
- endoscopic ultrasound (EUS) for staging
- bronchoscopy to detect tracheal invasion except for adeno- carcinoma of the distal 1/3 of the esophagus
Radiology
- CT of thorax, abdomen & pelvis to look for metastases
- PET scan for staging to look for metastases[3][9] (covered by Medicare)
- bone scan if patient has bone pain or elevated serum alkaline phosphatase
- barium swallow
Staging
see staging of esophageal cancer
Complications
- most cases are diagnosed at advanced stages after onset of symptoms
Differential diagnosis
- Schatzky ring: thin, smooth benign ring of mucosa proximal to the gastroesophageal junction
- gastric cancer
Management
- recommendations from[3]
- surgery (esophagectomy)
- in patients with metastatic regional lymphadenopathy, neoadjuvant chemotherapy followed by surgery confers a modest survival benefit relative to surgery alone[3]
- recommendations from[5]
- Stage 0 (Tis N0 M0), carcinoma in situ
- radiation followed by surgery (esophagectomy)
- > 90% 5 yr survival
- Stage 1 (T1 N0 M0)
- chemoradiation* followed by surgery (esophagectomy)
- > 50% 5 yr survival
- Stage 2a (T2-3 N0 M0)
- chemoradiation* followed by surgery (esophagectomy)
- 15-30% 5 yr survival
- Stage 2b (T1-2 N1 M0)
- chemoradiation* followed by surgery
- 10-30% 5 yr survival
- Stage 3 (T3 N1 M0 or T4 any N M0)
- chemoradiation*, palliative resection of T3a tumors
- <10% 5 yr survival
- Stage IV (any T any N M1)
- radiation therapy +/- intraluminal dilation & chemotherapy[5]
- chemotherapy plus immunotherapy nivolumab (MKSAP20)[3][12][14]
- 5 yr survival is rare
- 30-40% of total surgically resectable
- Stage 0 (Tis N0 M0), carcinoma in situ
- add trastuzumab to chemotherapy if HER2 positive
- adjuvant nivolumab improves disease-free survival[12]
- prognosis: 5 year survival is 15-25%[3]
- prevention
- regular NSAID use may reduce risk of esophageal adenocarcinoma[10]
* chemoradiation: two courses of 5-fluorouracil & cisplatin (Platinol) plus 40 Gy of radiation in 15 sessions over 3 weeks
* chemoradiation with fluoropyrimidine S-1 enhanced anticancer activity & reduced toxicity vs 5-fluorouracil & cisplatin in the elderly[13]
* epirubicin, cisplatin & 5-fluorouracil for 3 months before & 3 months after surgery (no radiation therapy)[3]
* cisplatin based therapy or cisplatin-based therapy + trastuzumab in patients with HER2 tumor expression[3]
More general terms
Additional terms
References
- ↑ Bonin et al, Cancer Management: A Multidisciplinary Approach, Chapter 5, 1999
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 281
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025 - ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 568-69
- ↑ 5.0 5.1 5.2 Cunningham D, Allum WH, Stenning SP et al Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. PMID: https://pubmed.ncbi.nlm.nih.gov/16822992
- ↑ Kleinberg L, Forastiere AA. Chemoradiation in the management of esophageal cancer. J Clin Oncol. 2007 Sep 10;25(26):4110-7. PMID: https://pubmed.ncbi.nlm.nih.gov/17827461
- ↑ Wang KK, Wongkeesong M, Buttar NS. American Gastroenterological Association technical review on the role of the gastroenterologist in the management of esophageal carcinoma. Gastroenterology. 2005 May;128(5):1471-505 PMID: https://pubmed.ncbi.nlm.nih.gov/15887129
- ↑ Varghese TK Jr, Hofstetter WL, Rizk NP et al The society of thoracic surgeons guidelines on the diagnosis and staging of patients with esophageal cancer. Ann Thorac Surg. 2013 Jul;96(1):346-56. Review. PMID: https://pubmed.ncbi.nlm.nih.gov/23752201
- ↑ 9.0 9.1 Healy MA, Yin H, Reddy RM, Wong SL. Use of positron emission tomography to detect recurrence and associations with survival in patients with lung and esophageal cancers. J Natl Cancer Inst 2016 Feb 22; 108:djv429 PMID: https://pubmed.ncbi.nlm.nih.gov/26903519
- ↑ 10.0 10.1 Bjorkman DJ NSAIDs Do Not Reduce Risk for Barrett Esophagus. Physician's First Watch, Sept 21, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Thrift AP et al. Nonsteroidal anti-inflammatory drug use is not associated with reduced risk of Barrett's esophagus. Am J Gastroenterol 2016 Aug 30 PMID: https://pubmed.ncbi.nlm.nih.gov/27575711 - ↑ 11.0 11.1 Yu C, Tang H, Guo Y et al Effect of Hot Tea Consumption and Its Interactions With Alcohol and Tobacco Use on the Risk for Esophageal Cancer: A Population-Based Cohort Study. Ann Intern Med. 2018. Feb 6. <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/29404576 <Internet> http://annals.org/aim/article-abstract/2671921/effect-hot-tea-consumption-its-interactions-alcohol-tobacco-use-risk
Kamangar F, Freedman ND Hot Tea and Esophageal Cancer. Ann Intern Med. 2018. Feb 6. <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/29404600 <Internet> http://annals.org/aim/article-abstract/2671922/hot-tea-esophageal-cancer - ↑ 12.0 12.1 12.2 Kelly RJ, Ajani JA, Kuzdzal J et al Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med 2021; 384:1191-1203. April 1. PMID: https://pubmed.ncbi.nlm.nih.gov/33789008 https://www.nejm.org/doi/full/10.1056/NEJMoa2032125
- ↑ 13.0 13.1 Ji Y, Du X, Zhu W et al Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer. A Multicenter Randomized Phase 3 Clinical Trial. JAMA Oncol. Published online August 5, 2021 PMID: https://pubmed.ncbi.nlm.nih.gov/34351356 https://jamanetwork.com/journals/jamaoncology/fullarticle/2782741
Eads JR, Haller DG Primary Chemoradiotherapy for Older Patients With Esophageal Cancer. JAMA Oncol. Published online August 5, 2021 PMID: https://pubmed.ncbi.nlm.nih.gov/34351378 https://jamanetwork.com/journals/jamaoncology/fullarticle/2782745 - ↑ 14.0 14.1 Doki Y, Ajani JA, Kato K, et al; CheckMate 648 Trial Investigators. Nivolumab combination therapy in advanced esophageal squamous-cell carcinoma. N Engl J Med. 2022;386:449-62. PMID: https://pubmed.ncbi.nlm.nih.gov/35108470
- ↑ Joseph A, Raja S, Kamath S, et al. Esophageal adenocarcinoma: a dire need for early detection and treatment. Cleve Clin J Med. 2022;89:269-279. PMID: https://pubmed.ncbi.nlm.nih.gov/35500930
- ↑ National Cancer Institute Esophageal Cancer - Health Professional version https://www.cancer.gov/types/esophageal/hp
Patient information
esophageal cancer patient information