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Oesophageal Cancer

Oesophageal cancer –

 

Eighth  most common incident cancer world wide -extremely aggressive nature and poor survival rate ( 5 yr survival is around 15 % to 25 % )
 Two main histological subtypes oesophageal adenocarcinoma 
( from columnar glandular cells ) and oesophageal squamous cell carcinoma (from stratified squamous epithelial lining )
 Risk factors , location , natural histories tend to differ substantially and globally more than 85 % of all incident OeCa cases are SCC’s
 A highly fatal disease which is a global health problem , the GLOBOCAN project estimates that 572,034 new cases of OeCa which represents 3.2 % of all new cancers diagnosed globally and 508,585 deaths happened in 2018
 No screening or surveillance algorithm till now has proven to be sufficient in discriminatory accuracy or external validation to support use in clinical practice.

 

Two geographical belts with high incidence of OeCa along north central China through the Central Asian republics to N Iran and 2nd from eastern to Southern Africa

 

Predominant subtype worldwide Affects the upper part of oesophagus More common in black individuals and white woman Incidence increases with age and tends to peak in 7th decade Risk factors include -
○ smoking ○ excess alcohol ○ diet ( tea , mate and coffee have been studied ) ○ chewing or areca nut often mixed with tobacco ○ pre-existing anatomical diseases ( as achalasia ,caustic strictures , gastrectomy and atrophic gastritis ) ○ Plummer-Vinson’s syndrome and ○ Tylosis ( an autosomal dominant disease ) Smoking is strongly associated with ESCC Transition models have described squamous epithelium undergoing inflammatory changes that proceed to dysplasia and subsequently in situ malignant changes ESCC is 2-3 times more common in males Role / association of Human Papilloma Virus and ESCC remains controversial.

 

Predominant subtype in US & Europe 8 times more common in men than in women & 5 fold more common in whites compared to blacks in the US Develops at the junction of the oesophagus and stomach Arises in areas of esophagus where the squamous epithelium is replaced by columnar-lined metaplastic epithelium ( Barrett oesophagus ) usually due to presence of gastro-esophageal reflux Risk factor include
○ gastro-esophageal reflux disease ○ Barrett’s oesophagus ( screening and surveillance remain controversial ) ○ obesity ○ tobacco smoking and dietary factors ( low fruit and veg diet )

It has been reported that weekly symptoms of GORD/GERD increased the odd of developing OeCa by 5 fold whereas daily symptoms increased the risk by 7 fold

Patients with Barrett’s esophagus ( BE ) usually found during endoscopy have a 30-60 fold increase in the incidence of EAC although the annual absolute risk of developing EAC is 0.12 % With a rise on obesity ,GORD and Barrett’s oesophagus ,understandably adenocarcinoma has become the leading histological subtype in Western nations ( widely quoted as change in epidemiology of OeCa ) Use of proton pump inhibitors.

 

Tobacco and alcohol act synergistically to increase the risk of esophageal cancer , particularly SCC High intake of fruits and vegetable is protective It is also thought that deficiencies of Vit A , E , selenium and zinc also contribute towards development of OeCa Long term use of NSAIDs and aspirin are associated with a decreased risk of OeCa Helicobacter pylori – a meta analysis has shown negative association with ESCC in East Asians but no effect on Western populations.

 

Barrett’s oesophagus- Presence of > 1 cm of metaplastic columnar epithelium which has replaced the normal stratified squamous epithelium which lines the distal oesophagus.

 

Risk factors- chronic GORD symptoms< 5 yrs advancing age male cigarette smoking central obesity Caucasian race Family h/o BE

 

Risk factors for development of neoplasia – advancing age increasing length of BE central obesity cigarette smoking lack of NSAID usage lack of PPI use lack of statin usage.

 

Decision on surveillance would be a decision taken by the gastroenterology team based on agreed guidance , patient preference and circumstances.

 

Presentation Lack of early clinical symptoms – hence often diagnosed in advanced stages Symptoms vary by stage Seen more commonly with increased age ( median age of diagnosis is 67 and majority of cases are diagnosed in people aged 65-74 yrs Subtle non specific symptoms as
○ retrosternal discomfort
○ burning sensation
○ cough , dyspnoe , hoarseness 
○ pain which can be in the abdomen , back or retrosternal Dysphagia – usually indicates T2 ot T3 disease
○ due to locally advanced cancer causing obstruction
○ first for solid food and to liquids in advanced stages Loss of appetite Regurgitation of food Reflux symptoms ( EAC up to 2/3rd of patients ) Cachexia
○ multifactorial syndrome
○ loss of fat and skeletal muscle mass and systemic inflammation due to complex host-tumour interactions , implies that patients are malnourished and often unable to tolerate treatment
○ eating difficulties further compound the problem Weight loss GI bleeding may manifest as haematemesis , melena and anaemia.

 

Exam – Early stages – examination usually unremarkable Barrett’s oesophagus is an endoscopic finding Patients with advanced disease may have hepatomegaly , pleural effusion and supraclavicular lymphadenopathy Weight loss , cachexia , anorexia in advanced disease.

 

Management – Diagnosis is via endoscopy and biopsy Staging can be done by CT , Positron- emission tomography , endo-esophageal ultrasound ( TNM staging system ) Treatment is multimodal and includes chemotherapy , radiation therapy following surgical resection or without surgical resection Multidisciplinary/multimodal approach which includes surgeons , gastroenterologists ,medical oncologists , radiation oncologists , dietitians , pathologists is recommended to improve survival In the early stages of malignancy surgery still remains the only viable option of cure Despite advances in endoscopic techniques esophagectomy ( minimally invasive esophagectomy ) is associated with considerable pot-operative morbidity Laparoscopy – to check for metastases to peritoneum ,liver & celiac lymph node Bronchoscopy may be needed to evaluate spread to trachea , bronchi Role of aspects in treatment as preferred neoadjuvant treatment 
( chemotherpay and chemoradiotherapy ) , anastomotic technique , extent of lymphadenectomy , organizatoion of post operative care and role of surgery beyond locally advanced disease are subject of ongoing debate ie optimal management is not yet defined.

 

dysphagia or
 aged 55 and over with weight loss and any of the following
○ upper abdominal pain
○ reflux
○ dyspepsia Urgent direct access upper GI endoscopy within 2 weeks

 

Haematemesis- Consider non-urgent direct access upper GI endoscopy to assess for cancer.

 

People over 55 with
 treatment resistant dyspepsia OR
 upper abdominal pain with low Hb OR
 raised platelet count with any of the following
○ nausea
○ vomiting
○ weight loss
○ reflux
○ dyspepsia
○ upper abdominal pain OR
 nausea and vomiting with any of the following
○ weight loss
○ reflux
○ dyspepsia
○ upper abdominal pain Consider non-urgent direct access upper GI endoscopy to assess for oesophageal cancer.

 

For patients with inoperable disease dysphagia presents a very distressing element along with pain , nausea , vomiting , malnutrition , anxiety , depression Dysphagia can be managed with
○ interventions
○ dietary modifications Interventions includes
○ endoscopic procedures aimed at minimizing the size of the tumour
○ opening the compressed oesophagus with various methods as dilatation , stent placement and ablative procedures
○ surgical options include palliative resections and bypass surgeries
○ radiation therapy is often used and chemotherapy to reduce disease burden to improve symptoms ( endoluminal and external beam or brachytherapy )
○ laser Dietary measures include small meals taken , liquid diets 
○ gastrostomy tubes or total parenteral nutrition Optimal treatment for palliative management of dysphagia remains controversial.

References

  1. Zhang, Yuwei. “Epidemiology of esophageal cancer.” World journal of gastroenterology vol. 19,34 (2013): 5598-606. doi:10.3748/wjg.v19.i34.5598
  2. Thrift, A.P. Global burden and epidemiology of Barrett oesophagus and oesophageal cancer. Nat Rev Gastroenterol Hepatol (2021). https://doi.org/10.1038/s41575-021-00419-3
  3. Uhlenhopp, D.J., Then, E.O., Sunkara, T. et al. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol 13, 1010–1021 (2020). https://doi.org/10.1007/s12328-020-01237-x ( Abstract )

  4. Domper Arnal, María José et al. “Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries.” World journal of gastroenterology vol. 21,26 (2015): 7933-43. doi:10.3748/wjg.v21.i26.7933
  5. Vaghjiani RG, Molena D. Surgical management of esophageal cancer. Chin Clin Oncol. 2017 Oct;6(5):47. doi: 10.21037/cco.2017.07.05. PMID: 29129087. ( Abstract )
  6. Kelly RJ. Emerging Multimodality Approaches to Treat Localized Esophageal Cancer. J Natl Compr Canc Netw. 2019 Aug 1;17(8):1009-1014. doi: 10.6004/jnccn.2019.7337. PMID: 31390584.
    ( Abstract )
  7. Lin SH, Chang JY. Esophageal cancer: diagnosis and management. Chin J Cancer. 2010 Oct;29(10):843-54. doi: 10.5732/cjc.010.10151. PMID: 20868553. ( Abstract )
  8. Anandavadivelan P, Lagergren P. Cachexia in patients with oesophageal cancer. Nat Rev Clin Oncol. 2016 Mar;13(3):185-98. doi: 10.1038/nrclinonc.2015.200. Epub 2015 Nov 17. PMID: 26573424.
    ( Abstract )
  9. Huang FL, Yu SJ. Esophageal cancer: Risk factors, genetic association, and treatment. Asian J Surg. 2018 May;41(3):210-215. doi: 10.1016/j.asjsur.2016.10.005. Epub 2016 Dec 13. PMID: 27986415. ( Abstract )
  10. Short MW, Burgers KG, Fry VT. Esophageal Cancer. Am Fam Physician. 2017 Jan 1;95(1):22-28. PMID: 28075104.
  11. Recio-Boiles A, Babiker HM. Esophageal Cancer. [Updated 2020 Nov 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459267/
  12. Abbas, Ghulam, and Mark Krasna. “Overview of esophageal cancer.” Annals of cardiothoracic surgery vol. 6,2 (2017): 131-136. doi:10.21037/acs.2017.03.03
  13. Epidemiology, Risk Factors and Clinical Manifestations of Esophageal Cancer Talar Tatarian et al Shackelford’s Surgery of Alimentary Tract Chapter 35 , 362-367
  14. Hanna, W C et al. “What is the optimal management of dysphagia in metastatic esophageal cancer?.” Current oncology (Toronto, Ont.) vol. 19,2 (2012): e60-6. doi:10.3747/co.19.892
  15. Ramakrishnaiah, Vishnu Prasad Nelamangala et al. “Palliation of Dysphagia in Carcinoma Esophagus.” Clinical medicine insights. Gastroenterology vol. 9 11-23. 6 Jun. 2016, doi:10.4137/CGast.S30303
  16. Shaheen, Nicholas J MD, MPH, FACG1; Falk, Gary W MD, MS, FACG2; Iyer, Prasad G MD, MSc, FACG3; Gerson, Lauren B MD, MSc, FACG4 ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus, American Journal of Gastroenterology: January 2016 – Volume 111 – Issue 1 – p 30-50 doi: 10.1038/ajg.2015.322
  17. Suspected cancer: recognition and referral NICE guideline [NG12]Published:  Last updated: 

 

 

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