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Tom Frazierfrazier Objectivesobjectives TomTom FrazierFrazier ObjectivesObjectives AchalasiaAchalasia EverythingEverything inin ddsepddsep Pathophysiology SomeSome extrasextras Epidemiology VideoVideo Symptomatology Diagnosis Complications Treatment PathophysiologyPathophysiology degeneration of the myenteric inhibitory neurons imbalance between excitatory and inhibitory elements Intact cholinergic, excitatory neural function ? autoimmune response to a viral insult in genetically susceptible individuals HSV/Zoster/others Circulating autoantibodies Inflammatory infiltrate class II HLA DQw1 The American Journal of Gastroenterology Vol. 100, 6 Pages: 1404-1414 The American Journal of Gastroenterology Vol. 100, 6 Pages: 1404-1414 HistopathologyHistopathology ofof AchalasiaAchalasia Mild normal inflammation Loss of Severe inflammtion ganglion cells Walzer N, Hirano I. Gastroenterology Clinics - Volume 37, Issue 4 (December 2008) SecondarySecondary formsforms ofof achalasiaachalasia Achalasia Achalasia secondary to cancer Postoperative (antireflux fundoplication, bariatric (pseudoachalasia) gastric banding) Squamous cell carcinoma of the esophagus Allgrove's syndrome (AAA syndrome) Adenocarcinoma of the esophagus Eosinophilic esophagitis Gastric adenocarcinoma Hereditary cerebellar ataxia Lung carcinoma Familial achalasia Leiomyoma Sjogren's syndrome LyLymphomamphoma Sarcoidosis Breast adenocarcinoma Post vagotomy Hepatocellular carcinoma Autoimmune polyglandular syndrome type II Reticulum cell sarcoma Lymphangiomphangioma Achalasia with generalized motility disorder Metastatic renal cell carcinoma Chagas' disease (Trypanosoma cruzi) Mesothelioma Chagas' disease (Trypanosoma cruzi) Metastatic prostate carcinoma Multiple endocrine neoplasia, type IIb (Sipple's Pancreatic adenocarcinoma syndrome) Neurofibromatosis (von Recklinghausen's disease) Paraneoplastic syndrome (anti-Hu antibody) Parkinson's disease Amyloidosis Fabry's disease Hereditary cerebellar ataxia Achalasia with associated Hirschsprung's disease Hereditary hollow visceral myopathy WhoWho getsgets it?it? IncidenceIncidence 1/100,0001/100,000 PrevalencePrevalence 1/10,0001/10,000 MaleMale == female,female, allall agesages mostmost commonlycommonly presentspresents inin patientspatients betweenbetween thethe agesages ofof 2525 andand 6060 yearsyears SymptomatologySymptomatology DysphagiaDysphagia toto solidssolids andand liquidsliquids isis thethe mostmost commoncommon presentingpresenting symptomsymptom RegurgitationRegurgitation isis thethe secondsecond mostmost commoncommon symptomsymptom NocturnalNocturnal regurgitationregurgitation ofof esophagealesophageal contentscontents cancan leadlead toto nighttimenighttime coughcough andand aspirationaspiration DifficultyDifficulty belchingbelching isis reportedreported inin aa largelarge proportionproportion ofof patientspatients SymptomatologySymptomatology absent belch reflex ~ upper airway obstruction secondary to a massively dilated esophagus that extrinsically compresses the posterior aspect of the trachea. Weight loss occurs in end-stage disease and usually does not exceed 5 to 10 kg before patients seek medical attention Chest pain is reported in 20% to 60% of patients. Improvement in pain does not necessarily accompany improvement in dysphagia after either pneumatic dilation or Heller myotomy Heartburn is reported in a large number of patients with achalasia (counterintuitive) SymptomatologySymptomatology ProgressiveProgressive symptomssymptoms << 66 monthsmonths inin patientspatients >> 6060 yearsyears withwith weightweight lossloss andand difficultdifficult passagepassage ofof thethe endoscopeendoscope acrossacross thethe esophagogastricesophagogastric junctionjunction increaseincrease thethe likelihoodlikelihood ofof aa patientpatient havinghaving cancercancer-- associatedassociated achalasiaachalasia DiagnosisDiagnosis EGDEGD endoscopyendoscopy normalnormal ~~ 44%44% ofof patientspatients withwith achalasiaachalasia DifficultyDifficulty traversingtraversing thethe esophagogastricesophagogastric junctionjunction shouldshould raiseraise suspicionsuspicion forfor pseudoachalasiapseudoachalasia duedue toto neoplasticneoplastic infiltrationinfiltration ofof thethe distaldistal esophagusesophagus oror gastricgastric cardia.cardia. distended with retained food and saliva stasis esophagitis Walzer N, Hirano I. Gastroenterology Clinics - Volume 37, Issue 4 (December 2008) DiagnosisDiagnosis BEBE esophagealesophageal dilatationdilatation withwith retainedretained foodfood andand bariumbarium andand aa smoothsmooth taperedtapered constrictionconstriction ofof thethe gastroesophagealgastroesophageal junctionjunction thethe diagnosisdiagnosis ofof achalasiaachalasia waswas suggestedsuggested inin onlyonly 64%64% ofof bariumbarium examinationsexaminations DiagnosisDiagnosis ManometryManometry RequiredRequired forfor diagnosisdiagnosis No peristalsis OftenOften seenseen butbut notnot requiredrequired forfor diagnosisdiagnosis Incomplete LES relaxation Elevated LES pressure Higher intraesophageal baseline than gastric baseline CanCan’’tt distinguishdistinguish 11ºº fromfrom 22ºº •Absent esophageal peristalsis (required to diagnose achalasia) •Elevated LES pressure •Poor LES relaxation VigorousVigorous AchalasiaAchalasia defineddefined byby thethe presencepresence ofof normalnormal toto highhigh amplitudeamplitude esophagealesophageal bodybody contractionscontractions inin thethe presencepresence ofof aa nonrelaxingnonrelaxing LES.LES. esophagealesophageal contractilecontractile waveswaves withwith amplitudesamplitudes inin excessexcess ofof 4040 mmmm HgHg PreviouslyPreviously thoughtthought toto bebe thethe earlyearly formform andand moremore amendableamendable toto treatmenttreatment HRMHRM High resolution esophageal manometry (HRM) improves the accuracy of esophageal manometry. Manometric variants of achalasia exist. achalasia with minimal esophageal pressurization (type I, classic), achalasia with esophageal compression (type II), achalasia with spasm (type III), and ****type II and III = “Vigorous Achalasia” they are distinct in terms of their responsiveness to medical or surgical therapies. type II = strong positive predictor of response type III= strong negative predictor of response HRM HRM Gastroenterology. 2008 Sep;135(3):756-69. HRM HRM Gastroenterology. 2008 Sep;135(3):756-69. ComplicationsComplications associatedassociated withwith AchalasiaAchalasia progressive malnutrition aspiration pna epiphrenic diverticula immediately proximal to the LES potential therapeutic technical challenges and perforation risks. esophageal cancer SCC > adeno No difference in treatment groups 16-fold increased risk during years 1 to 24 after initial diagnosis ↓ LES pressure places = ↑ risk for esophageal acid exposure and development of Barrett's esophagus. AchalasiaAchalasia andand SCCSCC Walzer N, Hirano I. Gastroenterology Clinics - Volume 37, Issue 4 (December 2008) TreatmentTreatment PrimaryPrimary objectiveobjective == reducereduce thethe LESLES basalbasal pressurepressure medicalmedical therapytherapy botulinumbotulinum toxintoxin injectioninjection pneumaticpneumatic dilationdilation surgicalsurgical myotomymyotomy American Journal of Gastroenterology Vol. 94, 12 Pages: 3406-3412 TreatmentTreatment MeasuringMeasuring TreatmentTreatment GoalsGoals ObjectiveObjective measuresmeasures measurements of LES pressure and esophageal emptying barium radiographs, nuclear scintigraphy, possibly esophageal impedance. timed barium esophagram LES pressure < 10 mm Hg has been shown to be a significant predictor of long-term response to pneumatic dilation MedicalMedical TherapyTherapy patientspatients whowho areare awaitingawaiting oror unableunable toto toleratetolerate moremore invasiveinvasive treatmenttreatment modalities.modalities. NitratesNitrates calciumcalcium channelchannel antagonistsantagonists sildenafilsildenafil AllAll areare limitedlimited byby efficacyefficacy andand sideside effectseffects BotulinumBotulinum ToxinToxin targetstargets thethe excitatory,excitatory, acetylcholineacetylcholine-- releasingreleasing neuronsneurons thatthat generategenerate LESLES basalbasal musclemuscle tone.tone. AA totaltotal ofof 8080 toto 100100 UU ofof thethe toxintoxin isis injectedinjected inin divideddivided dosesdoses intointo thethe fourfour quadrantsquadrants ofof thethe LESLES TheThe effecteffect ofof intermittentintermittent versusversus scheduledscheduled dosingdosing ofof botulinumbotulinum toxintoxin onon clinicalclinical efficacyefficacy hashas notnot beenbeen studied.studied. BotulinumBotulinum ToxinToxin 1515 prospectiveprospective studiesstudies ~~ 450450 patientspatients ResponseResponse ratesrates atat 11 monthmonth averageaverage 78%78% (range,(range, 63%63% toto 90%).90%). 66 months,months, raterate dropsdrops toto 58%58% (range,(range, 25%25% toto 78%)78%) 1212 monthsmonths toto 49%49% (range,(range, 15%15% toto 64%).64%). ?? ProtectiveProtective antibodiesantibodies (additional(additional injectionsinjections areare =/<)=/<) PredictorsPredictors ofof responseresponse toto botulinumbotulinum toxintoxin age > 50 years presence of vigorous achalasia BotulinumBotulinum ToxinToxin residualresidual LESLES pressurepressure postpost botulinumbotulinum toxintoxin hashas averagedaveraged approximatelyapproximately 2020 mmmm Hg.Hg. (need(need <10mHg)<10mHg) SideSide effects:effects: transienttransient chestchest painpain (~20%)(~20%) andand heartburnheartburn (5(5--10%)10%)
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