High Incidence of Esophageal Squamous Cell Carcinoma in the Kalenjin Population of Kenya Chris Huff, MD PGY-3

M.C. 54 yo female presents with worsening SOB and dry cough x 1 month. Also mild dysphagia with solids. Denies chest pain, orthopnea, PND, LE swelling. No fever, chills, night sweats, hemoptysis PMH: none Fam Hx: NC Soc Hx: no toxic habits Meds: none All: NKDA

M.C. EXAM: Gen: mild resp distress VS: 36.8, P85, BP90/60, R26, 88% RA Heart: RRR, no m/r/g Lungs: coarse breath sounds throughout all lung fields bilaterally Abd: benign, no HSM Node: no palpable LAD Ext: warm, no edema

M.C. HCT 32 WBC 8 Plt 250 Creat 1.2 Na+ 128 HIV (-) CXR – diffuse interstitial opacities bilat. with mediastinal LAD

M.C. Hospital Course: -Admitted to the medicine service and treated empirically with Rocephin, Azithromycin, and 4 drug TB therapy -Worsened over the next few days, so steroids and nebulizer initiated -On HD #5 sats 35% on 15L

M.C. -Patient transferred to the ICU with plan for intubation -Pt intubated and after inflation of the cuff, was discovered to have persistent air leak -Also stomach and chest both rising with bagging

M.C. -Patient was felt to most likely have tracheo-esophageal fistula (TEF) -Gen Surg consulted for EGD and cancer found in mid portion of esophagus with extension to the trachea, creating TEF -Pt made comfort care and expired 1 hr later from resp. failure

Esophageal SCC in Western Kenya Epidemiology: - Most common cancer in Men and 3 rd most common in women - Most common cancer in Men and 3 rd most common in women - Incidence 200 per 100,000 -Male to female ratio of 1.5 to 1 -Mean age at diagnosis 58.7 yrs -90% is squamous cell

Esophageal SCC in Western Kenya Tenwek Hospital Bomet Kenya - Retrospective Review of esophageal cancer diagnoses Retrospective Review of esophageal cancer diagnoses Esophageal cancer accounted for 914 (34%) of newly diagnosed cancers - Esophageal cancer accounted for 914 (34%) of newly diagnosed cancers - 6.3% of pts </= to 30yo, 1% </= to 20yo - 6.3% of pts </= to 30yo, 1% </= to 20yo Dis Esophagus May 15.

Esophageal SCC in Western Kenya Risk Factors: -Family history -EtOH and tobacco -Corn and Wheat Diet (2 main hypotheses) 1) Deficiency of A, C, E, selenium, zinc 2) Exposure to the corn mold Fusarium moniliforme Sheldon 3) Polycyclic Aromatic Hydrocarbons from food contaminated with smoke or soot

Esophageal SCC in Western Kenya Pathophysiology: -Arises from polyps, plaques, or denuded epithelium -Usually occurs in the mid-esophagus -Early invasion of submucosa and extends in cephalad direction -Invades lymph nodes early b/c the lymphatics are located in the lamina propria

Esophageal SCC in Western Kenya Clinical Manifestations: -Dysphagia and weight loss most common -Vomiting and chest pain -Iron deficiency anemia without melena -Respiratory symptoms if TEF develops

Esophageal SCC in Western Kenya Tracheoesophageal Fistula: How rare? - European study in of 2113 patients with esophageal cancer were found to have a TEF - European study in of 2113 patients with esophageal cancer were found to have a TEF -Incidence in Kenya unknown

Esophageal SCC in Western Kenya Diagnosis of Esophageal Cancer: - Barium swallow can suggest, but need EGD with biopsy to make the diagnosis - Barium swallow can suggest, but need EGD with biopsy to make the diagnosis - On EGD can appear as plaque, stricture, ulceration, or mass - On EGD can appear as plaque, stricture, ulceration, or mass - Diagnosis improves with number of biopsies taken: 1= 93%, 7=98% - Diagnosis improves with number of biopsies taken: 1= 93%, 7=98%

Esophageal SCC in Western Kenya

Staging of Esophageal Cancer: - TNM criteria – 5 yr survival related to stage: - TNM criteria – 5 yr survival related to stage: I 60% II 31% III 20% IV 4%

Esophageal SCC in Western Kenya Staging of Esophageal Cancer: - CT scan to evaluate for metastasis (M) - CT scan to evaluate for metastasis (M) - EUS for locoregional staging (T & N) - EUS for locoregional staging (T & N) - Possible PET to better eval for mets prior to surgery - Possible PET to better eval for mets prior to surgery **EUS and PET not available in Western Kenya and staging CT often not performed because of financial reasons

Esophageal SCC in Western Kenya Treatment: Depends on Stage - Neoadjuvant chemoradiation followed by surgery for stage I – IIIa - Neoadjuvant chemoradiation followed by surgery for stage I – IIIa - Cisplatin/5-FU chemo recommended - Cisplatin/5-FU chemo recommended - 60% unresectable at diagnosis - 60% unresectable at diagnosis - Chemoradiation - Palliative care (may include stenting)

Conclusions Esophageal Cancer is common and occurs at an early age in Western Kenya Risk factors are combination of genetic and environmental Diagnosis made with EGD and biopsy In remote areas of Kenya treatment limited to surgical resection vs palliative care

References Balazs et al. Eur J Cardiothorac Surg 2008;34: Parker et al. Frequent occurrence of esophageal cancer in young people in western Kenya Dis Esophagus May 15 Wakhisi et al. Esophageal cancer in north rift valley of Western Kenya. Afr Health Sci Jun;5(2): White et al. Esophageal Cancer: a common malignancy of young people in Bomet District, Kenya. Lancet Aug 10;360(9331): Graham et al. Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma.Gastroenterology 1982 Feb;82(2): Rationale of staging in cancer of the esophagus. In: International Trends in General Thoracic Surgery: Esophageal Cancer, vol 4, Delarue, N, Wilkins, EW, Wong, J Eds), CV Mosby, St Louis Mallery, S, Van Dam, J. Increased rate of complete EUS staging of patients with esophageal cancer using the nonoptical, wire-guided echoendoscope. Gastrointest Endosc 1999; 50:53. Bolton, JS, Fuhrman, GM, Richardson, WS. Esophageal resection for cancer. Surg Clin North Am 1998; 78:773.