Author(s): J. Stuart Wolf, Jr., M.D., 2009License: Unless otherwise noted, this material is made available under the terms...
Citation Key                          for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Ada...
Kidney and   Upper Urinary Tract            J. Stuart Wolf, Jr., M.D.              Professor of UrologyFall 2008
Michigan Urology Center University of Michigan    Ann Arbor, MI
Kidney and Upper Urinary TractSyllabus  !    If I show you graphics that are NOT in       your syllabus        !    Then t...
Kidney and Upper Urinary TractObjectives  !    Appreciate importance, evaluation, and       differential diagnosis of hema...
Kidney and Upper Urinary TractClinically-Oriented Lecture            Hematuria   Evaluation and Differential     Case pres...
HematuriaHematuria  !    Definition        !    > 3 RBC / hpf in urinary sediment        !    Dipstick is screening test o...
HematuriaHematuria  !    Additional Characterization        !    Gross (grossly visible) or microscopic?              –  G...
HematuriaEvaluation 1: Examine Urine  !    In women, get cath. UA if > 1 squamous       cell / hpf (vaginal contamination)...
HematuriaEvaluation 1: Examine Urine  !    Is there pyuria or bacteruria?        " Probable   infection (any GU site)  !  ...
HematuriaEvaluation 2: History and Physical  !    Flank Pain        "  Stone  !    Dysuria, bladder irritability        " ...
HematuriaEvaluation 2: History and Physical  !    Trauma, or intense physical activity        "  May    be cause of hematu...
HematuriaEvaluation 2: History and Physical  !    Visible blood at urethral meatus        "  Urethral    source  !    Feve...
HematuriaEvaluation 3: Labs and Procedures  !    Formal urinalysis with microscopic       examination  !    Urine culture ...
HematuriaDiagnostic Categories  !    Infection  !    Calculi  !    Cancer  !    Benign neoplasms / lesions  !    Other obs...
HematuriaInfection  !    Kidney        !  Pyelonephritis - parenchyma        !  Pyonephrosis - pus in collecting system   ...
HematuriaInfection  !    Bladder        !  Bacterial cystitis  !    Prostate        !  Bacterial prostatitis  !    Urethra...
HematuriaCalculi  !    Kidney        !  Obstructive vs. Non-obstructive        !  Simple vs. Staghorn  !    Ureter        ...
HematuriaCancer  !    Kidney        !  Renal cell carcinoma, other  !    Upper collecting system        !  Urothelial, oth...
HematuriaBenign Neoplasms / Lesions  !    Kidney        !  Simple cysts        !  Cystic renal diseases        !  Angiomyo...
HematuriaOther Obstructions  !    Ureter        !  Ureteropelvic junction (UPJ)        !  Intrinsic strictures        !  E...
HematuriaTrauma / Exertional Hematuria  !    Cannot be assumed to be causeMedical Renal Disease  !    Previous Nephrology ...
Kidney & Upper Urinary TractKidney, Intra-renal Collecting System, and Ureter  !    Topics covered (case presentations)   ...
Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO)  !    24 year old woman  !    L...
Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO)  !    Young age - diagnosed mos...
Kidney & Upper Urinary Tract: ObstructionAnatomy of Kidney and Upper Urinary Tract  !    Paired Kidneys  !    Urine from c...
Kidney & Upper Urinary Tract: Obstruction                Calyx          Renal PelvisInfundibulumJ.S. Wolf
Kidney & Upper Urinary Tract: ObstructionAnatomy of Kidney and Upper Urinary Tract  !    Tight spots     prone to obstruct...
Gray s Anatomy
Gray s Anatomy
Image removed
Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO) Evaluation  !    Intravenous ur...
IntravenousUrogram                             Left                                    hydronephrosis                     ...
Diuretic Renal Scintigraphy   Source UndeterminedExcretion from left kidney is delayed
Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO) Treatment  !    Percutaneous en...
Kidney & Upper Urinary Tract: ObstructionCauses of UPJO !    Primary       !  Histological disorganization           –  ex...
Kidney & Upper Urinary Tract: ObstructionEvaluation of UPJO  !    Determine presence and degree of        obstruction     ...
Kidney & Upper Urinary Tract: ObstructionDilation of the Urinary Tract  !    Non-obstructive        !  Ureteral reflux, pr...
Massive Vesico-ureteral Reflux on Cystogram               Source Undetermined
Kidney & Upper Urinary Tract: ObstructionEvaluation of UPJO  !    Anatomic tests        !  Intravenous urography        ! ...
IntravenousUrography  Normal  kidney                                    Hydronephrosis              Source Undetermined
Renal Ultrasonography     Hydronephrosis    Source Undetermined
Computed TomographyCan determine additional anatomy, includingvessels crossing at UPJ          Source Undetermined
Computed TomographyCan determine additional anatomy, includingvessels crossing at UPJ             Source Undetermined
Endoluminal UltrasonographyCan detect vessels crossing over UPJ, butrequires retrograde catheterization            Source ...
Ultrasonography with Resistive Indices(PSV - LDV) /PSV: Normal    Diastolic flow velocity is preserved    Source Undetermi...
Ultrasonography with Resistive Indices(PSV - LDV) /PSV: Obstructed   Source Undetermined As resistance to blood flow incre...
Diuretic Renal Scintigraphy: mostdefinitive non-invasive testT ! = Time for ! of radiotracer to beexcreted from kidney aft...
Whitaker Test: most definitive testPressure in renal pelvis at set infusion ratethrough nephrostomy tube (> 15 mmHg at15 c...
Kidney & Upper Urinary Tract: ObstructionTreatment of UPJO                                          Most !    Open pyelopl...
Break
Kidney & Upper Urinary Tract: CalculiCase 2: Acutely Obstructing Distal Ureteral Calculus  !    30 year old man  !    Sudd...
Kidney & Upper Urinary Tract: CalculiCase 2: Acutely Obstructing Distal Ureteral Calculus  !    Sudden onset pain - c/w re...
Kidney & Upper Urinary Tract: CalculiSuspected Acute Ureteral Obstruction Differential Diagnosis  !    Intrinsic        ! ...
Kidney & Upper Urinary Tract: CalculiSuspected Acute Ureteral Obstruction Radiographic Evaluation  !    KUB and Intravenou...
Intravenous                                    This stoneUrography                           is less                      ...
Intravenous Urography                        This stone                        is faintly                        radio-   ...
Intravenous Urography                        … and is                        easier to                        identify whe...
Kidney & Upper Urinary Tract: CalculiSpontaneous Passage of Ureteral Stones                   Width         ProximalMiddle...
Ultrasonography                      HydronephrosisSource Undetermined
(almost) allComputed Tomography   stones dense                      on CTSource Undetermined
Computed Tomography     Source UndeterminedSecondary signs of ureteral obstruction
Computed Tomography      Source UndeterminedSecondary signs of ureteral obstruction
ComputedUrography            Source Undetermined
Intravenous Urography                      Irregular                      Filling                      DefectSource Undete...
Kidney & Upper Urinary Tract: CalculiIf        filling defect    on contrast study …     !    Neoplasm           !  Urothe...
Kidney & Upper Urinary Tract: CalculiCase 3: Non-obstructing Renal Calculus  !    65 year old man  !    Microscopic hematu...
PlainRadiography Densely radio- opaque stones              Source Undetermined
Kidney & Upper Urinary Tract: CalculiIndications for Surgical Treatment of  Urolithiasis  !    Urinary tract infection  ! ...
PlainRadiography Staghorn Calculus              Source Undetermined
Kidney & Upper Urinary Tract: CalculiSurgical Treatment of Urolithiasis  !    Open surgical / laparoscopic      Most      ...
Source Undetermined
Source Undetermined
Image removed
Source Undetermined
Source Undetermined
Source Undetermined
Kidney & Upper Urinary Tract: CalculiParameters Determining Treatment of Urolithiasis  !    Size  !    Location  !    Comp...
Kidney & Upper Urinary Tract: CalculiSize  !    Small       !    SWL  !    Moderate       !    Ureteroscopy  !    Large   ...
Kidney & Upper Urinary Tract: CalculiLocation  !    Distal Ureter        !    Scope > SWL  !    Middle Ureter        !    ...
Computed Tomography     Source UndeterminedDistal aspect of UVJ, almost in bladder
Computed TomographySource Undetermined          Huge bilateral renal calculi
Kidney & Upper Urinary Tract: CalculiComposition  !    Dense (Calcium oxalate monohydrate)        !  Scope  !    Fuzzy/ Fa...
PlainRadiography Densely radio- opaque stone              Source Undetermined
Plain Radiography   Fuzzy  radio-  opaque  stone Source Undetermined
Kidney & Upper Urinary Tract: PyelonephritisCase 4: Pyelonephritis  !    29 year old woman  !    Started with 3 days of dy...
Kidney & Upper Urinary Tract: PyelonephritisCase 4: Pyelonephritis  !    Young woman - UTI is common  !    Initial cystiti...
Kidney & Upper Urinary Tract: PyelonephritisAcute Pyelonephritis  !    Most common disease of the kidney  !    Usually asc...
Source Undetermined            Lobar Nephronia
Kidney & Upper Urinary Tract: PyelonephritisManagement of Acute Pyelonephritis  !    Typical case - fever resolves within ...
Kidney & Upper Urinary Tract: PyelonephritisManagement of Acute Pyelonephritis  !    History of complications or lack of  ...
Kidney & Upper Urinary Tract: PyelonephritisDrainage procedures  !    Percutaneous nephrostomy tube                      I...
Break
Kidney & Upper Urinary Tract: Masses & Cysts Case 5: Renal Cell Carcinoma (RCC)   !    64 year old man   !    Gross hematu...
Kidney & Upper Urinary Tract: Masses & Cysts Case 5: Renal Cell Carcinoma (RCC)   !    Older man - peak in 6th decade, 3:1...
Kidney & Upper Urinary Tract: Masses & Cysts Demographics of RCC   !    Incidence: 12.8 per 100,000 ( 00 - 04)   !    Mort...
Kidney & Upper Urinary Tract: Masses & Cysts Risk factors for RCC   !    Cigarettes   !    Obesity   !    Hypertension   !...
Kidney & Upper Urinary Tract: Masses & Cysts Pathology of RCC   !    Proximal tubular cell neoplasm   !    Often venous in...
Kidney & Upper Urinary Tract: Masses & CystsCommon Renal Tumors  Pathology        Malignant?   Relative %  Renal Cell Ca. ...
Kidney & Upper Urinary Tract: Masses & Cysts Histology    !    Most Renal Cell Carcinomas have          Clear cell histolo...
Kidney & Upper Urinary Tract: Masses & Cysts Genetics    !    Most renal cell carcinomas are sporadic    !    Are associat...
Kidney & Upper Urinary Tract: Masses & Cysts Genetics    !    Von-Hippel Lindau syndrome          !  Autosomal dominant   ...
Kidney & Upper Urinary Tract: Masses & Cysts Symptoms / Signs of RCC   !    Hematuria (29 – 60%)   !    Flank pain (14 – 5...
Kidney & Upper Urinary Tract: Masses & Cysts  Paraneoplastic Syndromes     !    ESR elevation     !    Calcium elevation  ...
Kidney & Upper Urinary Tract: Masses & Cysts Central Role of Imaging    Simple Cyst             Benign Indeterminate      ...
Kidney & Upper Urinary Tract: Masses & Cysts Stage Migration of RCC due to   more frequent imaging   !    1970 s         !...
Kidney & Upper Urinary Tract: Masses & Cysts Imaging Modalities    !    Intravenous Urography (IVU, IVP)    !    Ultrasono...
Kidney & Upper Urinary Tract: Masses & CystsIntravenous Urography  !    Typical upper tract imaging for hematuria       wo...
IntravenousUrography  Mass Effect  in kidney                Source Undetermined
Kidney & Upper Urinary Tract: Masses & Cysts Ultrasonography   !    Usual follow-up to IVU suspicious for        renal mas...
Ultrasonography      Simple CystSource Undetermined
Kidney & Upper Urinary Tract: Masses & CystsSonographic Characteristics  !    Anechoic with enhanced through       transmi...
Ultrasonography          Renal StoneSource Undetermined
UltrasonographyNodule in CystSource Undetermined
UltrasonographySource Undetermined                      Solid Mass
Kidney & Upper Urinary Tract: Masses & Cysts Computed Tomography   !    Current gold standard   !    Non-contrast scan, th...
Computed TomographySource Undetermined                      Simple Cyst
Computed Tomography Source Undetermined                       Complex Cyst
Source Undetermined  Renal Cell Carcinoma
Kidney & Upper Urinary Tract: Masses & CystsSolid, Enhancing Renal Mass on CT is RCC until Proven Otherwise  !    Other po...
Source Undetermined                      Oncocytoma ?
AngiomyolipomaSource Undetermined
Renal AbscessSource Undetermined
Renal LymphomaSource Undetermined
Kidney & Upper Urinary Tract: Masses & Cysts Magnetic Resonance Imaging   !    Currently no advantage over CT except      ...
Magnetic Resonance Imaging Source Undetermined                       Thick Cyst Wall
MagneticResonanceImagingTumorThrombusin VenaCava            Source Undetermined
Kidney & Upper Urinary Tract: Masses & Cysts Sensitivity for Diagnosis of  RCC < 3 cm   !    Intravenous urography   - 67%...
Kidney & Upper Urinary Tract: Masses & CystsEvaluation of Suspected RCC  !    Initial imaging study (often IVU or US, eith...
Kidney & Upper Urinary Tract: Masses & CystsStaging and Management of RCC !    Stage I       !    Tumor < 7 cm limited to ...
Kidney & Upper Urinary Tract: Masses & CystsStaging and Management of RCC !    Stage III       !    Tumor into vein, fat, ...
Kidney & Upper Urinary Tract: Masses & Cysts Prognosis of RCC                            5 year survival   !    Stage I   ...
Kidney & Upper Urinary Tract: Masses & CystsCase 6: Autosomal Dominant Polycystic Kidney Disease (ADPKD)   !    37 year ol...
Kidney & Upper Urinary Tract: Masses & CystsCase 6: Autosomal Dominant Polycystic Kidney Disease (ADPKD)  !    Middle-aged...
Kidney & Upper Urinary Tract: Masses & CystsADPKD !    Autosomal dominant inheritance       !    85% from PKD1 mutation (1...
Kidney & Upper Urinary Tract: Masses & CystsADPKD !    Epithelial proliferation in renal tube ! renal      tubule become c...
ADPKDSource Undetermined
Source Undetermined
Kidney & Upper Urinary Tract: Masses & CystsOther Cystic Diseases of the Kidney  !    Simple cysts        !    In populati...
ACKDSource Undetermined
Kidney & Upper Urinary Tract: Masses & Cysts Evaluation of Renal Cysts   !    Simple cysts definable with US         !  No...
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10.08.08: Diseases of the Kidney Upper Urinary Tract

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10.08.08: Diseases of the Kidney Upper Urinary Tract

  1. 1. Author(s): J. Stuart Wolf, Jr., M.D., 2009License: Unless otherwise noted, this material is made available under the terms ofthe Creative Commons Attribution–Share Alike 3.0 License:http://creativecommons.org/licenses/by-sa/3.0/We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use,share, and adapt it. The citation key on the following slide provides information about how you may share and adapt thismaterial.Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions,corrections, or clarification regarding the use of content.For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use.Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or areplacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to yourphysician if you have questions about your medical condition.Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  2. 2. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation LicenseMake Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  3. 3. Kidney and Upper Urinary Tract J. Stuart Wolf, Jr., M.D. Professor of UrologyFall 2008
  4. 4. Michigan Urology Center University of Michigan Ann Arbor, MI
  5. 5. Kidney and Upper Urinary TractSyllabus !  If I show you graphics that are NOT in your syllabus !  Then they are NOT critical for the test !  They are to familiarize you with Urologic operative techniques, for their interest rather than for testing purposes !  Radiography will be on test, but not the actual images
  6. 6. Kidney and Upper Urinary TractObjectives !  Appreciate importance, evaluation, and differential diagnosis of hematuria !  Gain basic understanding of major disease processes of kidney and upper tract !  Obstruction !  Calculi !  Infection !  Renal masses and cysts
  7. 7. Kidney and Upper Urinary TractClinically-Oriented Lecture Hematuria Evaluation and Differential Case presentations of representative entities
  8. 8. HematuriaHematuria !  Definition !  > 3 RBC / hpf in urinary sediment !  Dipstick is screening test only !  Dipstick is 95 % sensitive, but only about ~ 80% specific !  In population with 10% hematuria, PPV of Dipstick is only 35% !  Positive Dipstick indicates hematuria ONLY when confirmed by microscopy of > 3 RBC / hpf
  9. 9. HematuriaHematuria !  Additional Characterization !  Gross (grossly visible) or microscopic? –  Gross more likely significant !  If gross, is it initial (urethra), terminal (bladder neck or prostate), or total (interior of bladder or upper tract)
  10. 10. HematuriaEvaluation 1: Examine Urine !  In women, get cath. UA if > 1 squamous cell / hpf (vaginal contamination) !  Is color red but dipstick - ? " Consider phenolphthalein, rhodamine B, others !  Is dipstick + but no RBC present? " Beware if specific gravity < 1.008 (RBC may have been there, but lysed) " Usually false positive test " Unfortunately, a common referral
  11. 11. HematuriaEvaluation 1: Examine Urine !  Is there pyuria or bacteruria? " Probable infection (any GU site) !  Is there proteinuria (> 2 + on dipstick), or are there dysmorphic RBCs or RBC casts? " Probable glomerulonephritis
  12. 12. HematuriaEvaluation 2: History and Physical !  Flank Pain "  Stone !  Dysuria, bladder irritability "  Bladder or prostate infection !  Sickle cell, diabetes "  Papillary necrosis !  Family or personal history of calculi, PCKD, other GU / Neph diseases "  Possible familial trait
  13. 13. HematuriaEvaluation 2: History and Physical !  Trauma, or intense physical activity "  May be cause of hematuria !  Tobacco use, occupational chemical exposure (aromatic dyes) "  Risk for renal and urothelial cancers
  14. 14. HematuriaEvaluation 2: History and Physical !  Visible blood at urethral meatus "  Urethral source !  Fever, CVAT "  Pyelonephritis !  Prostate exam "  Prostatitis, Prostate cancer !  Pelvic Exam "  Urethral, vaginal, or labial lesions
  15. 15. HematuriaEvaluation 3: Labs and Procedures !  Formal urinalysis with microscopic examination !  Urine culture !  If infection is DOCUMENTED, then can omit rest of work-up if hematuria clears with antibiotics !  IVU versus KUB + US versus CT !  +/- Urine cytology !  +/- Serum electrolytes and creatinine !  Cystoscopy
  16. 16. HematuriaDiagnostic Categories !  Infection !  Calculi !  Cancer !  Benign neoplasms / lesions !  Other obstruction !  Trauma / exertional hematuria !  Medical renal disease !  Blood dyscrasia / anticoagulation !  Benign familial hematuria
  17. 17. HematuriaInfection !  Kidney !  Pyelonephritis - parenchyma !  Pyonephrosis - pus in collecting system !  Renal abscess - pus pocket in parenchyma
  18. 18. HematuriaInfection !  Bladder !  Bacterial cystitis !  Prostate !  Bacterial prostatitis !  Urethra !  Infectious urethritis
  19. 19. HematuriaCalculi !  Kidney !  Obstructive vs. Non-obstructive !  Simple vs. Staghorn !  Ureter !  Obstructive vs. Non-obstructive !  Bladder
  20. 20. HematuriaCancer !  Kidney !  Renal cell carcinoma, other !  Upper collecting system !  Urothelial, other !  Bladder !  Urothelial, other !  Urethra !  Squamous cell, other !  Prostate !  Adenocarcinoma, other
  21. 21. HematuriaBenign Neoplasms / Lesions !  Kidney !  Simple cysts !  Cystic renal diseases !  Angiomyolipoma, other neoplasms !  Ureter !  Hemangioma, other !  Bladder !  Endometrioma, other !  Urethra !  Condyloma, other
  22. 22. HematuriaOther Obstructions !  Ureter !  Ureteropelvic junction (UPJ) !  Intrinsic strictures !  Extrinsic obstruction !  Bladder !  Bladder outlet obstruction (BOO) –  Benign prostatic hyperplasia (BPH) –  Other !  Urethra –  Strictures, other
  23. 23. HematuriaTrauma / Exertional Hematuria !  Cannot be assumed to be causeMedical Renal Disease !  Previous Nephrology lectureBlood Dyscrasia / Anticoagulation !  Cannot be assumed to be causeBenign Familial Hematuria !  Microscopic only, negative work-up
  24. 24. Kidney & Upper Urinary TractKidney, Intra-renal Collecting System, and Ureter !  Topics covered (case presentations) !  Ureteral obstruction (UPJO) !  Calculi (ureteral, renal) !  Infection (pyelonephritis) !  Cancer (renal cell carcinoma) !  Renal cystic disease (ADPKD)
  25. 25. Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO) !  24 year old woman !  Long history of intermittent left flank pain, recently worsening !  Not during sleep !  Especially notices after fluid intake, or even more after drinking alcohol !  No significant medical history
  26. 26. Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO) !  Young age - diagnosed mostly in children, variable after that !  Intermittent symptoms - typical of adult presentation !  Pain increased with fluid intake !  Classic for UPJO !  Flow-dependent obstruction (like a slow but not-yet clogged drain)
  27. 27. Kidney & Upper Urinary Tract: ObstructionAnatomy of Kidney and Upper Urinary Tract !  Paired Kidneys !  Urine from collecting tubules that terminate in papillae drain into: !  Calyces, that coalesce into !  Infundibula, which drain into !  Renal Pelvis !  Travels down ureter (peristalsis)
  28. 28. Kidney & Upper Urinary Tract: Obstruction Calyx Renal PelvisInfundibulumJ.S. Wolf
  29. 29. Kidney & Upper Urinary Tract: ObstructionAnatomy of Kidney and Upper Urinary Tract !  Tight spots prone to obstruction !  Ureteropelvic junction (UPJ) !  Mid-ureter as crosses iliac vessels (over sacrum on plain radiograph) !  Ureterovesical junction (UVJ) !  Of these, the UPJ most common site of congenital obstruction
  30. 30. Gray s Anatomy
  31. 31. Gray s Anatomy
  32. 32. Image removed
  33. 33. Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO) Evaluation !  Intravenous urogram !  Unilateral hydronephrosis and non- visualization of ureter !  Diuretic renal scintigraphy !  50% split renal function !  T 1/2 (time for ! of tracer to exit kidney) on symptomatic side > 100 minutes (normal < 10 minutes)
  34. 34. IntravenousUrogram Left hydronephrosis and non- visualization of the ureter Source Undetermined
  35. 35. Diuretic Renal Scintigraphy Source UndeterminedExcretion from left kidney is delayed
  36. 36. Kidney & Upper Urinary Tract: ObstructionCase 1: Ureteropelvic Junction Obstruction (UPJO) Treatment !  Percutaneous endopyelotomy !  A minimally-invasive alternative to formal pyeloplasty !  Nephro-ureteral stent capped off in 1 week, and removed in 6 weeks !  Complete resolution
  37. 37. Kidney & Upper Urinary Tract: ObstructionCauses of UPJO !  Primary !  Histological disorganization –  excess longitudinal muscle fibers (loss of normal organization) –  increase in collagen –  attenuation of muscle bundles !  Crossing vessels, high insertion, kinks, bands !  Secondary !  Traumatic scar, iatrogenic scar, external compression (think cancer!)
  38. 38. Kidney & Upper Urinary Tract: ObstructionEvaluation of UPJO !  Determine presence and degree of obstruction !  Is there obstruction, or just dilation? !  Complete or partial obstruction? !  Determine renal function !  If kidney not working well, may be little value in repairing !  Determine cause of obstruction
  39. 39. Kidney & Upper Urinary Tract: ObstructionDilation of the Urinary Tract !  Non-obstructive !  Ureteral reflux, prior obstruction, extra- renal pelvis, diuresis !  Stagnation may lead to infection and calculi, but usually innocuous !  Obstructive !  Increased resistance to urine flow that produces increased proximal pressure and subsequent loss of organ function !  Occasionally difficult to distinguish from non-obstructive
  40. 40. Massive Vesico-ureteral Reflux on Cystogram Source Undetermined
  41. 41. Kidney & Upper Urinary Tract: ObstructionEvaluation of UPJO !  Anatomic tests !  Intravenous urography !  Renal (surface) ultrasonography !  Computed tomography !  Endoluminal ultrasonography !  Functional tests !  Ultrasonography with resistive indices !  Diuretic renal scintigraphy !  Whitaker test
  42. 42. IntravenousUrography Normal kidney Hydronephrosis Source Undetermined
  43. 43. Renal Ultrasonography Hydronephrosis Source Undetermined
  44. 44. Computed TomographyCan determine additional anatomy, includingvessels crossing at UPJ Source Undetermined
  45. 45. Computed TomographyCan determine additional anatomy, includingvessels crossing at UPJ Source Undetermined
  46. 46. Endoluminal UltrasonographyCan detect vessels crossing over UPJ, butrequires retrograde catheterization Source Undetermined
  47. 47. Ultrasonography with Resistive Indices(PSV - LDV) /PSV: Normal Diastolic flow velocity is preserved Source Undetermined
  48. 48. Ultrasonography with Resistive Indices(PSV - LDV) /PSV: Obstructed Source Undetermined As resistance to blood flow increases, diastolic flow velocity decreases, and resistive index increases (R.I. > 0.70)
  49. 49. Diuretic Renal Scintigraphy: mostdefinitive non-invasive testT ! = Time for ! of radiotracer to beexcreted from kidney after furosemide T ! = 5 minutes T ! = 25 minutes (normal < 10 min.) (obstructed > 15 min.) Sources Undetermined
  50. 50. Whitaker Test: most definitive testPressure in renal pelvis at set infusion ratethrough nephrostomy tube (> 15 mmHg at15 cc/min infusion = obstruction) Source Undetermined
  51. 51. Kidney & Upper Urinary Tract: ObstructionTreatment of UPJO Most !  Open pyeloplasty Invasive / Most Effective !  Laparoscopic pyeloplasty !  Percutaneous endopyelotomy !  Retrograde balloon dilation Least !  Retrograde endopyelotomy Invasive / Least !  Acucise® (cutting balloon) endopyelotomy Effective
  52. 52. Break
  53. 53. Kidney & Upper Urinary Tract: CalculiCase 2: Acutely Obstructing Distal Ureteral Calculus !  30 year old man !  Sudden onset of right flank pain !  Initial gross hematuria, but now clear !  No fevers and chills, but nausea !  Frequent urination !  Pain somewhat less after a few hours !  Restless, moving about !  Right flank, lower quadrant, and testicular pain / tenderness !  5 - 10 RBC / hpf on urinalysis
  54. 54. Kidney & Upper Urinary Tract: CalculiCase 2: Acutely Obstructing Distal Ureteral Calculus !  Sudden onset pain - c/w renal colic !  Urine cleared - suggests obstruction !  Nausea - very common with renal colic !  Freq. urination - irritation by distal calculi !  Pain decreased - forniceal rupture, decrease in pressure from renal hemodynamics !  Moving about - NOT peritonitis !  Flank to scrotum - expected radiation !  Urinalysis - RBCs in 85%
  55. 55. Kidney & Upper Urinary Tract: CalculiSuspected Acute Ureteral Obstruction Differential Diagnosis !  Intrinsic !  Calculi, tumor, clot, edema !  Extrinsic !  Compression by tumor, lymph node !  Acute versus acute-on-chronic !  Calculi, or calculi impacted into partially- obstructing stricture? !  Clot, or clot on tumor?
  56. 56. Kidney & Upper Urinary Tract: CalculiSuspected Acute Ureteral Obstruction Radiographic Evaluation !  KUB and Intravenous urography !  Anatomic picture, localize pathology !  Ultrasonography !  CT !  Non-contrast (stones) !  CT urogram (with contrast, like IVU) !  Retrograde pyelography !  Injection through catheter
  57. 57. Intravenous This stoneUrography is less dense than contrast material, so appears as filling defect Source Undetermined
  58. 58. Intravenous Urography This stone is faintly radio- opaque … Source Undetermined
  59. 59. Intravenous Urography … and is easier to identify when contrast material comes down to it Source Undetermined
  60. 60. Kidney & Upper Urinary Tract: CalculiSpontaneous Passage of Ureteral Stones Width ProximalMiddle Distal 4 mm 20% 45% 55% 5 mm 6% 30% 45% 6 mm 0% 10% 25% 100% 50% 0% 1 2 3 4 5 6 7 8 9 10 J.S. Wolf
  61. 61. Ultrasonography HydronephrosisSource Undetermined
  62. 62. (almost) allComputed Tomography stones dense on CTSource Undetermined
  63. 63. Computed Tomography Source UndeterminedSecondary signs of ureteral obstruction
  64. 64. Computed Tomography Source UndeterminedSecondary signs of ureteral obstruction
  65. 65. ComputedUrography Source Undetermined
  66. 66. Intravenous Urography Irregular Filling DefectSource Undetermined
  67. 67. Kidney & Upper Urinary Tract: CalculiIf filling defect on contrast study … !  Neoplasm !  Urothelial neoplasm most common !  Blood clot !  Will resolve during follow-up !  Radio-lucent calculus (15%) !  Other 85% are calcium containing !  Refers to appearance on plain film (all typical stones are opaque on CT scan) !  Radio-lucent stones are usually uric acid (only medically dissolvable stone) !  Need to rule-out tumor!
  68. 68. Kidney & Upper Urinary Tract: CalculiCase 3: Non-obstructing Renal Calculus !  65 year old man !  Microscopic hematuria !  Remote history of urolithiasis !  Mild prostatism !  Unremarkable PE except for prostatic enlargement !  Urinalysis - 10 RBC / hpf
  69. 69. PlainRadiography Densely radio- opaque stones Source Undetermined
  70. 70. Kidney & Upper Urinary Tract: CalculiIndications for Surgical Treatment of Urolithiasis !  Urinary tract infection !  Significant obstruction !  Pain refractory to oral medication !  Others !  Staghorn calculi - risk of urosepsis !  Long-standing ureteral calculi - eventual obstruction !  Occupational or lifestyle reasons
  71. 71. PlainRadiography Staghorn Calculus Source Undetermined
  72. 72. Kidney & Upper Urinary Tract: CalculiSurgical Treatment of Urolithiasis !  Open surgical / laparoscopic Most lithotomy Invasive / Most Effective !  Percutaneous nephrostolithotomy (Antegrade endoscopy) !  Ureteroscopy (Retrograde endoscopy) Least !  Extracorporeal shock wave Invasive / Least lithotripsy (SWL) Effective
  73. 73. Source Undetermined
  74. 74. Source Undetermined
  75. 75. Image removed
  76. 76. Source Undetermined
  77. 77. Source Undetermined
  78. 78. Source Undetermined
  79. 79. Kidney & Upper Urinary Tract: CalculiParameters Determining Treatment of Urolithiasis !  Size !  Location !  Composition !  Medical Condition, Patient Preference, Physician Preference
  80. 80. Kidney & Upper Urinary Tract: CalculiSize !  Small !  SWL !  Moderate !  Ureteroscopy !  Large !  Percutaneous nephrostolithotomy
  81. 81. Kidney & Upper Urinary Tract: CalculiLocation !  Distal Ureter !  Scope > SWL !  Middle Ureter !  Scope > SWL !  Proximal Ureter !  SWL > Scope ? !  Kidney !  SWL > Scope
  82. 82. Computed Tomography Source UndeterminedDistal aspect of UVJ, almost in bladder
  83. 83. Computed TomographySource Undetermined Huge bilateral renal calculi
  84. 84. Kidney & Upper Urinary Tract: CalculiComposition !  Dense (Calcium oxalate monohydrate) !  Scope !  Fuzzy/ Faint (Calcium oxalate dihydrate, calcium phosphate, struvite) !  SWL !  Cystine !  Scope !  Uric Acid !  SWL
  85. 85. PlainRadiography Densely radio- opaque stone Source Undetermined
  86. 86. Plain Radiography Fuzzy radio- opaque stone Source Undetermined
  87. 87. Kidney & Upper Urinary Tract: PyelonephritisCase 4: Pyelonephritis !  29 year old woman !  Started with 3 days of dysuria (painful urination), urinary frequency / urgency !  Now temp 101.7º C, right flank pain !  History !  Occ previous UTI !  Recently married !  Limited sexual activity before marriage, now active !  PE - Right CVAT
  88. 88. Kidney & Upper Urinary Tract: PyelonephritisCase 4: Pyelonephritis !  Young woman - UTI is common !  Initial cystitis (infection ascends) common and suggest UTI !  Systemic symptoms - distinguishes upper from lower tract UTI !  Previous UTI - helps establish her characteristic symptoms of UTI !  Sexual activity - predisposing factor for UTI in women !  CVAT - renal involvement
  89. 89. Kidney & Upper Urinary Tract: PyelonephritisAcute Pyelonephritis !  Most common disease of the kidney !  Usually ascending infection !  Diagnosis by clinical findings and urine culture (85% are GNR; E. Coli) !  Imaging used to detect complications or to assess for predisposing factors !  Complications: papillary necrosis, pyonephrosis, abscess, sepsis !  Predisposing factors: obstruction, calculi, vesico-ureteral reflux
  90. 90. Source Undetermined Lobar Nephronia
  91. 91. Kidney & Upper Urinary Tract: PyelonephritisManagement of Acute Pyelonephritis !  Typical case - fever resolves within 48 hrs of starting antibiotics !  Oral abx in most !  Intravenous abx if very ill-appearing !  Debilitated patients at greater risk !  Diabetes mellitus !  Steroids !  Chronically ill !  Immuno-suppressed
  92. 92. Kidney & Upper Urinary Tract: PyelonephritisManagement of Acute Pyelonephritis !  History of complications or lack of response to antibiotics "  US or CT for obstruction, calculi !  Upper tract obstruction with infection "  DRAINAGE (stent, percutaneous tube) !  Upper tract calculus with infection "  Treat acute infection, then calculus !  If child or recurrent "  US for scars "  Voiding cystogram for reflux
  93. 93. Kidney & Upper Urinary Tract: PyelonephritisDrainage procedures !  Percutaneous nephrostomy tube Image of a percutaneous nephrostomy tube removed !  Ureteral stent Hildpeyi, wikimedia commons
  94. 94. Break
  95. 95. Kidney & Upper Urinary Tract: Masses & Cysts Case 5: Renal Cell Carcinoma (RCC) !  64 year old man !  Gross hematuria !  Flank pain !  History !  66 pack-year smoker !  PE !  Fullness in right flank
  96. 96. Kidney & Upper Urinary Tract: Masses & Cysts Case 5: Renal Cell Carcinoma (RCC) !  Older man - peak in 6th decade, 3:1 M:F overall !  Hematuria - most common presenting sign !  Flank pain and flank mass - along with hematuria, the classic triad !  Smoking - major acquired risk factor
  97. 97. Kidney & Upper Urinary Tract: Masses & Cysts Demographics of RCC !  Incidence: 12.8 per 100,000 ( 00 - 04) !  Mortality: 4.2 per 100,000 ( 00 - 04) !  estimated 51,190 new cases in 2007 (~2% of adult malignancies) !  estimated 12,890 deaths in 2007 !  Lifetime Risk (M / F) !  Risk of occurrence - 1.71 / 1.01 % !  Risk of death - 0.59 / 0.35 % SEER Cancer Statistics
  98. 98. Kidney & Upper Urinary Tract: Masses & Cysts Risk factors for RCC !  Cigarettes !  Obesity !  Hypertension !  Occupational exposures !  Dialysis !  Hereditary !  von Hippel-Lindau disease !  Tuberous Sclerosis
  99. 99. Kidney & Upper Urinary Tract: Masses & Cysts Pathology of RCC !  Proximal tubular cell neoplasm !  Often venous involvement !  Hemorrhagic, necrotic, cystic, and calcified components common !  Metastasize most commonly to lung, liver, bone, adrenal, and contralateral kidney
  100. 100. Kidney & Upper Urinary Tract: Masses & CystsCommon Renal Tumors Pathology Malignant? Relative % Renal Cell Ca. Yes 85% Urothelial Ca. Yes 5% Oncocytoma No 5% Other Most not 5%
  101. 101. Kidney & Upper Urinary Tract: Masses & Cysts Histology !  Most Renal Cell Carcinomas have Clear cell histology !  Lipids (dissolve out during slide processing) and glycogen !  Fuhrman grading (1 to 4) –  1 = well differentiated –  4 = poorly differentiated
  102. 102. Kidney & Upper Urinary Tract: Masses & Cysts Genetics !  Most renal cell carcinomas are sporadic !  Are associated with several syndromes, the most common of which is Von- Hippel Lindau syndrome !  Autosomal dominant !  Cerebellar and retinal vascular tumors !  Adrenal and renal tumors (inc cysts)
  103. 103. Kidney & Upper Urinary Tract: Masses & Cysts Genetics !  Von-Hippel Lindau syndrome !  Autosomal dominant !  Mutation in VHL tumor suppressor gene: 3p25-26 !  95% of sporadic clear cell renal cell carcinomas have VHL mutation !  One of the strongest associations among solid tumors !  Opportunities for gene therapy
  104. 104. Kidney & Upper Urinary Tract: Masses & Cysts Symptoms / Signs of RCC !  Hematuria (29 – 60%) !  Flank pain (14 – 51%) !  Flank mass (21 – 47%) !  All 3 = Classic triad !  Present in < 10% !  Usually signifies advanced disease
  105. 105. Kidney & Upper Urinary Tract: Masses & Cysts Paraneoplastic Syndromes !  ESR elevation !  Calcium elevation !  Polycythemia !  Anemia !  Thrombophlebitis !  Hyperinsulinism !  LFT elevation
  106. 106. Kidney & Upper Urinary Tract: Masses & Cysts Central Role of Imaging Simple Cyst Benign Indeterminate Cyst ? Solid Mass Malignant
  107. 107. Kidney & Upper Urinary Tract: Masses & Cysts Stage Migration of RCC due to more frequent imaging !  1970 s !  4% of RCC < 3 cm !  32% presented with metastases !  1980 s !  25 - 40% were incidental finding !  25% of RCC < 3 cm !  17% presented with metastases !  1990 s !  60% were incidental finding
  108. 108. Kidney & Upper Urinary Tract: Masses & Cysts Imaging Modalities !  Intravenous Urography (IVU, IVP) !  Ultrasonography (US) !  Computed Tomography (CT) !  Magnetic Resonance Imaging (MRI)
  109. 109. Kidney & Upper Urinary Tract: Masses & CystsIntravenous Urography !  Typical upper tract imaging for hematuria work-up !  Excellent visualization of collecting system !  Renal mass or cyst causes displacement of surrounding organ or deformation of outline !  Screening study only !  If renal mass / cyst suspected, further imaging is required
  110. 110. IntravenousUrography Mass Effect in kidney Source Undetermined
  111. 111. Kidney & Upper Urinary Tract: Masses & Cysts Ultrasonography !  Usual follow-up to IVU suspicious for renal mass / cyst !  No ionizing radiation !  Non-invasive !  Operator dependent !  Reliably identifies simple cyst (85% of renal mass / cysts) !  If NOT a simple cyst !  Cross-sectional imaging
  112. 112. Ultrasonography Simple CystSource Undetermined
  113. 113. Kidney & Upper Urinary Tract: Masses & CystsSonographic Characteristics !  Anechoic with enhanced through transmission !  Simple cyst !  Echogenic with acoustic shadowing !  Stone or other calcification !  Iso / hypoechoic mass !  Solid mass
  114. 114. Ultrasonography Renal StoneSource Undetermined
  115. 115. UltrasonographyNodule in CystSource Undetermined
  116. 116. UltrasonographySource Undetermined Solid Mass
  117. 117. Kidney & Upper Urinary Tract: Masses & Cysts Computed Tomography !  Current gold standard !  Non-contrast scan, then scan with intravenous contrast !  Enhancement = Hounsfield units (density) increase by > 10 with contrast !  3 to 5 mm maximum cut width !  Spiral CT - single breath hold !  Minimize motion artifact !  Exact duplication of cuts
  118. 118. Computed TomographySource Undetermined Simple Cyst
  119. 119. Computed Tomography Source Undetermined Complex Cyst
  120. 120. Source Undetermined Renal Cell Carcinoma
  121. 121. Kidney & Upper Urinary Tract: Masses & CystsSolid, Enhancing Renal Mass on CT is RCC until Proven Otherwise !  Other possibilities !  Oncocytoma –  Benign, but indistinguishable from RCC on imaging !  Angiomyolipoma –  Benign, but can bleed if large –  Usually diagnosed by imaging fat !  Inflammatory mass –  History of febrile illness !  Lymphoma –  Malignant, but no surgery
  122. 122. Source Undetermined Oncocytoma ?
  123. 123. AngiomyolipomaSource Undetermined
  124. 124. Renal AbscessSource Undetermined
  125. 125. Renal LymphomaSource Undetermined
  126. 126. Kidney & Upper Urinary Tract: Masses & Cysts Magnetic Resonance Imaging !  Currently no advantage over CT except in certain situations !  Allergy to contrast material !  Elevated creatinine !  Distinguish wall in some cysts !  Detection of venous tumor thrombus in RCC (has replaced invasive venography)
  127. 127. Magnetic Resonance Imaging Source Undetermined Thick Cyst Wall
  128. 128. MagneticResonanceImagingTumorThrombusin VenaCava Source Undetermined
  129. 129. Kidney & Upper Urinary Tract: Masses & Cysts Sensitivity for Diagnosis of RCC < 3 cm !  Intravenous urography - 67% !  Ultrasonography - 79% !  Computed tomography - 94%
  130. 130. Kidney & Upper Urinary Tract: Masses & CystsEvaluation of Suspected RCC !  Initial imaging study (often IVU or US, either incidentally or for workup of hematuria or other signs / symptoms) !  CT or MRI for local assessment !  Define lesion !  Assess nodes, vein, other organs !  Staging !  CXR, Bloods, + Bone Scan and others
  131. 131. Kidney & Upper Urinary Tract: Masses & CystsStaging and Management of RCC !  Stage I !  Tumor < 7 cm limited to kidney (T1) !  no LN+ or metastases "  Radical or Partial Nephrectomy !  Stage II !  Tumor > 7 cm limited to kidney (T2) !  No LN+ or metastases "  Radical Nephrectomy
  132. 132. Kidney & Upper Urinary Tract: Masses & CystsStaging and Management of RCC !  Stage III !  Tumor into vein, fat, or adrenal !  Or one single LN+ "  Radical Nephrectomy !  Stage IV !  Tumor beyond Gerota s fascia (T4) !  Or > 1 LN+ Or metastases "  Systemic Therapy (Chemo, Immuno)
  133. 133. Kidney & Upper Urinary Tract: Masses & Cysts Prognosis of RCC 5 year survival !  Stage I ~90% !  Stage II ~80% !  Stage III ~40 - 60% !  Stage IV ~10%
  134. 134. Kidney & Upper Urinary Tract: Masses & CystsCase 6: Autosomal Dominant Polycystic Kidney Disease (ADPKD) !  37 year old woman !  No recent medical care !  Left flank fullness !  Adopted, unknown family history !  PE !  Mass in left flank !  BP 170/100
  135. 135. Kidney & Upper Urinary Tract: Masses & CystsCase 6: Autosomal Dominant Polycystic Kidney Disease (ADPKD) !  Middle-aged - usually diagnosed in third decade !  Fullness - HUGE bilateral cysts, symptomatic in ~15% !  Over 50% have family history !  Hypertension - almost always, given enough time
  136. 136. Kidney & Upper Urinary Tract: Masses & CystsADPKD !  Autosomal dominant inheritance !  85% from PKD1 mutation (16q13) !  15% from PKD2 mutation (4q21-23) !  Virtually 100% penetrance !  Incidence !  1 / 1000 live births !  6000 new cases annually !  Prevalence ~ 200,000
  137. 137. Kidney & Upper Urinary Tract: Masses & CystsADPKD !  Epithelial proliferation in renal tube ! renal tubule become cyst ! as cyst grows it compresses renal parenchyma !  < 1% tubules become cysts !  Also hepatic, pancreatic and splenic cysts, and cerebral aneurysms !  Hypertension !  Renal failure - most but not all, usually in 5th decade
  138. 138. ADPKDSource Undetermined
  139. 139. Source Undetermined
  140. 140. Kidney & Upper Urinary Tract: Masses & CystsOther Cystic Diseases of the Kidney !  Simple cysts !  In population over age 50 –  50% pathologically, 33% by CT !  Single or multiple !  Simple cyst complicated by hemorrhage or infection ( Complex cyst ) !  Acquired cystic kidney disease (ACKD) !  40% of dialysis patients by 3 years !  Controversial increase in RCC
  141. 141. ACKDSource Undetermined
  142. 142. Kidney & Upper Urinary Tract: Masses & Cysts Evaluation of Renal Cysts !  Simple cysts definable with US !  No further work-up needed !  ADPKD, ACKD !  Definable by history and PE !  Complex Cyst !  Simple cyst complicated by infection or hemorrhage !  Cystic renal cancer !  Diagnostic dilemma, surgery often required
  143. 143. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicySlide 28: Stuart WolfSlide 30: Gray s AnatomySlide 31: Gray s AnatomySlide 34: Source UndeterminedSlide 35: Source UndeterminedSlide 40: Source UndeterminedSlide 42: Source UndeterminedSlide 43: Source UndeterminedSlide 44: Source UndeterminedSlide 45: Source UndeterminedSlide 46: Source UndeterminedSlide 47: Source UndeterminedSlide 48: Source UndeterminedSlide 49: Source UndeterminedSlide 50: Source UndeterminedSlide 57: Source UndeterminedSlide 58: Source UndeterminedSlide 59: Source UndeterminedSlide 60: Stuart WolfSlide 61: Source UndeterminedSlide 62: Source UndeterminedSlide 63: Source UndeterminedSlide 64: Source UndeterminedSlide 65: Source UndeterminedSlide 66: Source UndeterminedSlide 69: Source UndeterminedSlide 71: Source Undetermined
  144. 144. Slide 73: Source UndeterminedSlide 74: Source UndeterminedSlide 76: Source UndeterminedSlide 77: Source UndeterminedSlide 78: Source UndeterminedSlide 82: Source UndeterminedSlide 83: Source UndeterminedSlide 85: Source UndeterminedSlide 86: Source UndeterminedSlide 90: Source UndeterminedSlide 93: Hildpeyi, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Ureteral_stent.jpg, CC:BY-SA, http://creativecommons.org/licenses/by-sa/3.0/deed.enSlide 110: Source UndeterminedSlide 112: Source UndeterminedSlide 114: Source UndeterminedSlide 115: Source UndeterminedSlide 116: Source UndeterminedSlide 118: Source UndeterminedSlide 119: Source UndeterminedSlide 120: Source UndeterminedSlide 122: Source UndeterminedSlide 123: Source UndeterminedSlide 124: Source UndeterminedSlide 125: Source UndeterminedSlide 127: Source UndeterminedSlide 128: Source UndeterminedSlide 138: Source UndeterminedSlide 139: Source UndeterminedSlide 141: Source Undetermined

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