EsophagealEsophageal CancerCancer

Valerie A. Williams, MD Division of Thoracic Surgery September 29, 2011 The Food for thought

• A muscular pump bordered by 2 sphincters

• One function: Transport

The unidirectional (aboral) movement of food/saliva

• No endocrine, exocrine, immunologic, digestive, absorptive or secretory functions PresentingPresenting SymptomsSymptoms

z Dysphagia z Odynophagia / chest pain z Weight loss z Hematemesis z Others

OverviewOverview

Cell Type Demo- Risk Factors Location Incidence graphics Squamous Black Etoh Proximal Declining carcinoma Males Smoking and Mid Diet-nitrosamines Esophagus Adenocarcinoma White Barrett’s Lower Increasing Males esophagus SquamousSquamous CellCell CarcinomaCarcinoma

Incidence by Geographic Location

600 Cases 500 per 400 100,000 300 200 100

US and Britian South Africa Kazakhstan and China HistologyHistology andand EsophagealEsophageal CancerCancer IncidenceIncidence (1975(1975––2001)2001)

AdenoCA

Squamous Cell CA

Unspecified

Pohl H, Welch HG. J Natl Cancer Inst 2005;97:142–6. RelativeRelative ChangeChange inin IncidenceIncidence ofof EsophagealEsophageal AdenocarcinomaAdenocarcinoma andand OtherOther MalignanciesMalignancies (1975(1975––2001)2001)

Esophageal AdenoCA

Melanoma Prostate Breast Colorectal

Pohl H, Welch HG. J Natl Cancer Inst 2005;97:142– 6 EvolutionEvolution ofof EsophagealEsophageal CancerCancer z In the U.S. and western Europe, the incidence of adenocarcinoma of the distal esophagus, GE junction and gastric cardia has increased by approximately 10% / yr over the past 30 years (now 10x incidence compared to 1976.) z 70-75% of all esophageal CA in the U.S. is now adenocarcinoma. EsophagealEsophageal CancerCancer

2010 Estimates z 16,640 new cases diagnosed in the U.S. ~ 70% adenocarcinoma (~11,000+ cases) z 14,500 deaths z 5-year relative survival (2001-2007) = 16.8% z Median age (2004-2008) = 68 years

NCI SEER Database, 2010 EstimatedEstimated USUS CancerCancer DeathsDeaths

Men Women 290,890 272,810 Lung & bronchus 32% 25% Lung & bronchus Prostate 10% 15% Breast Colon & 10% 10% Colon & rectum 5% 6% Ovary Leukemia 5% 6% Pancreas Non-Hodgkin 4% 4% Leukemia lymphoma 3% Non-Hodgkin Esophagus 4% lymphoma & intrahepatic 3% 3% Uterine corpus 2% Multiple myeloma Urinary bladder 3% 2% Brain/ONS ONS=OtherKidney nervous system. 3% Source: American Cancer Society, 2007. 24% All other sites All other sites 21% WhyWhy thethe IncreaseIncrease inin EsophagealEsophageal Adenocarcinoma?Adenocarcinoma?

z GERD? z Acid suppression therapy? z Obesity/diet? z Helicobacter pylori eradication? Carcinogenesis Sequence

Persons with recurrent GERD GERD symptoms have an 8-fold (Reflux of gastric/duodenal contents) increase in the risk of developing esophageal Squamous epithelial injury adenocarcinoma

Intestinal metaplasia of mucosa Lagergren,et al. NEJM (Barrett’s) 1999;340:825-31.

Low-grade dysplasia

High-grade dysplasia

Invasive carcinoma BarrettBarrett’’ss EsophagusEsophagus

Definition z Defined as any length of endoscopically visible columnar mucosa extending onto the esophagus z PLUS intestinal metaplasia on histologic examination – Short-segment: < 3cm – Long-segment: ≥ 3cm BarrettBarrett’’ss EsophagusEsophagus

Endoscopic Appearance BarrettBarrett’’ss EsophagusEsophagus

Carcinogenesis Sequence

No dysplasia

Low-grade dysplasia

High-grade dysplasia

Invasive carcinoma BarrettBarrett’’ss EsophagusEsophagus Surgical Considerations

No dysplasia Anti-reflux Surgery

Low-grade dysplasia

High-grade dysplasia

Esophagectomy Invasive carcinoma BarrettBarrett’’ss EsophagusEsophagus Management Controversies z Screening – Baseline on patients with GERD z When? z How often? z Surveillance – Serial on patients with known BE to R/O progression to dysplasia/CA z How often? z Are lives saved? z Ablation PrePre--OperativeOperative InvestigationsInvestigations forfor EsophagealEsophageal CarcinomaCarcinoma

• Flexible upper endoscopy with biopsies • Barium UGI • Computed tomography (CT) • Endoscopic ultrasound (EUS) • PET DiagnosisDiagnosis && StagingStaging z 50 y/o male z Dysphagia EGDEGD withwith biopsybiopsy Chest/AbdominalChest/Abdominal CTCT

z Evaluate for T4 disease and PET/PET/ CTCT ScanScan

• Radioactive sugar – (fluorodeoxyglucose ) is injected into the blood

• Uptaken by rapidly growing and active cells absorb large PETPET ScanScan

Liver Metastasis Primary tumor TT--stage/Depthstage/Depth ofof invasioninvasion z

Tis Intraepithelial

T1 Invades submucosa

T2 Invades muscularis propria

T3 Invades paraesophageal tissue

T4 Invades adjacent organ EndoscopicEndoscopic UltrasonographyUltrasonography (EUS)(EUS) EUSEUS EUSEUS Comparison EUS vs Pathology Proportion Correctly Predicted by EUS

100% 76.5% 82.4% 80% 60% 40% 20% 0% Basement Membrane Barrier Invasive cancer Critical Barriers Node rarely involved Systemic disease rare (< 2%) 5yr. Survival = 90%

Muscularis Mucosa Barrier Nodes likely involved (25%) Submucosa Few in number (0-5) Systemic disease possible (17-25%) 5yr. Survival = 75% Muscularis Propria Adventitial Barrier Nodes commonly involved (85%) Adventitia Many in number (3-14) Systemic disease common (60- 75%) 5yr. Survival = 30% 0.5-1cm Lymphatic Drainage

N Stage

N0 no lymph nodes

N1 1-2 lymph nodes

N2 3-6 lymph nodes

N3 7 or more lymph nodes ProgressionProgression ofof CarcinomaCarcinoma

Implications for Therapy

Local Regional Systemic

Surgery ChemoTx +Surgery ChemoRadTx (+/- XRT) 19131913 11st SuccessfulSuccessful EsophagectomyEsophagectomy by Franz John A. Torek

• Transthoracic esophagectomy

• 67-year-old woman who presented with progressive dysphagia and weight loss. 19131913 11st SuccessfulSuccessful EsophagectomyEsophagectomy

• Patient was fed through the tube for the first 8 post-op days

• Later received nutrition orally.

• Meal passed from the proximal esophageal stoma through an external tube to the gastrostomy

• Patient survived for 12 years SurgicalSurgical ResectionResection

z Prepare conduit - z Mobilize esophagus z Divide esophagus proximally and stomach distally z 5cm margins z Anastomosis between esophagus and stomach z Pyloroplasty Anatomy/VascularAnatomy/Vascular supplysupply EsophagectomyEsophagectomy OptionsOptions

Less z “Minimally invasive” esophagectomy invasive

z Transhiatal esophgecetomy

z Ivor Lewis Esophagectomy Right thoracotomy, , intrathoracic esophagogastrostomy

z 3 hole esophagectomy Right thoracotomy, laparotomy, cervical esophagogastrostomy

More z Radical (en bloc) esophagectomy Invasive – with 2-field lymphadenectomy – with 3-field lymphadenectomy Transhiatal Esophagectomy TranshiatalTranshiatal EsophagectomyEsophagectomy GastricGastric conduitconduit TranshiatalTranshiatal EsophagectomyEsophagectomy z Advantages – Avoid thoracotomy – Cervical anastomosis z Disadvantages – Blind mediastinal dissection – Less accurate staging – Inferior treatment/less lymphadenectomy IvorIvor LewisLewis EsophagectomyEsophagectomy TransthoracicTransthoracic (Ivor(Ivor Lewis)Lewis) z Advantages – Complete 2 – field lymphadenectomy – Less risk of blind mediastinal dissection z Disadvantages – Increased morbidity of thoracotomy – Intrathoracic leak has higher morbidity 33--holehole EsophagectomyEsophagectomy MIEMIE

ColonColon interpositioninterposition SurgicalSurgical ResectionResection ComplicationsComplications z Anastomotic leak z Pulmonary complications z Chylothorax z Recurrent laryngeal nerve injury z Airway injury EsophagectomyEsophagectomy MortalityMortality BasedBased onon HospitalHospital VolumeVolume Medicare Data, 1994-1999

24 20 16 Operative Mortality 12 (%) 8 4 0 <2 2-4 5-7 8-19 >19 Esophagectomies per year Birkmeyer JD, et al. NEJM 2002;346:1128-1137. Mortality After Esophagectomy for Cancer at U.S. Specialty Centers

Institution Resection Type* Year N Mortality (%) Brigham TTE 2001 250 3.6 Cornell 3-field en bloc 2002 80 5 USC THE/TTE/en bloc 2004 263 4.5 University of THE/TTE 2008 258 2.7 Rochester

*THE-Transhiatal esophagectomy; TTE-Transthoracic esophagectomy; MortalityMortality followingfollowing esophagectomyesophagectomy

z The perception: High z The reality: Not in experienced hands Not in the right patient population EvolutionEvolution inin ResectionResection forfor EarlyEarly EsophagealEsophageal NeoplasiaNeoplasia Emphasis on Decreased Morbidity and Improved Quality of Life Transthoracic esophagectomy (TTE)

Transhiatal esophagectomy (THE)

Minimally invasive esophagectomy (MIE)

Endoscopic resection (ER) (and ablation) MethodsMethods toto EliminateEliminate EsophagealEsophageal MucosaMucosa

z Thermal – MPEC “Burn it” – APC – Nd:YAG laser – RF ablation (BarrX) “Freeze it” z Cryotherapy “Laser it” z PDT (photodynamic therapy) z Mucosectomy “Resect it” – Endoscopic – Surgical II.. EndoscopicEndoscopic MucosalMucosal ResectionResection (EMR)(EMR) TechniquesTechniques ofof EMREMR

Soetikno, R. et al. J Clin Oncol 2005; 23:4490-4498

RisksRisks ofof EMREMR z 1) Procedural Complications – Perforation – Stricture – Bleeding z 2) Inadequate Treatment – Positive margins (deep or lateral) – Untreated synchronous lesions – Associated nodal disease II.II. RadiofrequencyRadiofrequency AblationAblation ofof BarrettBarrett’’ss EsophagusEsophagus

z HALO360 and HALO90 systems (BÂRRX Medical) HALOHALO RFRF EnergyEnergy GeneratorGenerator HALOHALO360360 AblationAblation CatheterCatheter HALOHALO9090 FDA Approved April, 2006 RF ablation Ablation Target depth (avoids stricture) Muscularis mucosae (Ablation Target Depth) G Submucosa with G esophageal glands

EMR and PDT Depth Muscularis propria

Surgical Depth Courtesy of BÂRRX Medical Courtesy of BÂRRX Medical Courtesy of BÂRRX Medical EndoscopicEndoscopic AppearanceAppearance

Baseline, 4 cm IM Immediate Slough EffectEffect ofof RFRF AblationAblation

Barrett’s with LGD 12 Months Post-Treatment (Pretreatment) PotentiallyPotentially CurativeCurative EndoscopicEndoscopic TherapiesTherapies forfor EarlyEarly EsophagealEsophageal NeoplasiaNeoplasia

III. Cryotherapy CryoSprayCryoSpray AblationAblation™™

SurgerySurgery ForFor EsophagealEsophageal CancerCancer z The incidence of esophageal adenocarcinoma continues to rise at an alarming rate! z Esophageal adenocarcinoma is related to Barrett’s esophagus which, in turn, is related to GERD. z “Improvements” in the medical therapy for GERD have done nothing to halt the progression of esophageal CA. SurgerySurgery ForFor EsophagealEsophageal CancerCancer Summary z In experienced hands, esophagectomy can be performed safely and with good quality of life. z Esophagectomy, alone or in combination with chemoTx/XRT, remains the gold standard of treatment for potentially curable disease. z Endoscopic therapies are evolving as curative therapy for early when the potential for nodal metastasis is low TreatmentTreatment ofof EsophagealEsophageal CancerCancer

The Future z Improved prognosis will depend upon: – Improved prevention (control of GERD) – Improved screening, earlier detection – Improved systemic therapies! TreatmentTreatment ofof EsophagealEsophageal CancerCancer The Future z Improved , immunotherapy or cytologic regimens z Tumor markers to predict potential for nodal/systemic spread, prognosis and the response to chemotherapy The End