Renal Masses and Cysts - Open.Michigan

Renal Masses and Cysts - Open.Michigan

Author(s): J. Stuart Wolf, Jr., M.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons AttributionShare 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 this material. Copyright holders of content included in this material should contact [email protected] 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 a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician 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. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicy Use + 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 License Make 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. Kidney and Upper Urinary Tract J. J. Stuart Stuart Wolf, Wolf, Jr., Jr., M.D. M.D. Professor Professor of of Urology Urology Fall 2008 Michigan Urology Center University of Michigan Ann Arbor, MI Kidney and Upper Urinary Tract Syllabus Syllabus

IfIf II show show you you graphics graphics that that are are NOT NOT in in your your syllabus syllabus Then they are NOT critical for the test Then they are NOT critical for the test They They are are to to familiarize familiarize you you with with Urologic Urologic operative operative techniques, techniques, for for their their interest interest rather

rather than than for for testing testing purposes purposes Radiography will be on test, but not the Radiography will be on test, but not the actual actual images images Kidney and Upper Urinary Tract Objectives Objectives Appreciate Appreciate importance, importance, evaluation, evaluation, and and differential differential diagnosis diagnosis of of hematuria hematuria Gain basic understanding of major disease Gain basic understanding of major disease processes processes of

of kidney kidney and and upper upper tract tract Obstruction Obstruction Calculi Calculi Infection Infection Renal Renal masses masses and and cysts cysts Kidney and Upper Urinary Tract Clinically-Oriented Lecture Hematuria Evaluation and Differential

Case presentations of representative entities Hematuria Hematuria Hematuria Definition Definition > 3 RBC / hpf in urinary sediment > 3 RBC / hpf in urinary sediment Dipstick is screening Dipstick is screening test test only only Dipstick % sensitive, sensitive, but Dipstick is is 95 95 % but only only about about ~~ 80% 80% specific specific

In population with 10% hematuria, PPV of In population with 10% hematuria, PPV of Dipstick Dipstick is is only only 35% 35% Positive Dipstick indicates Positive Dipstick indicates hematuria hematuria ONLY ONLY when when confirmed of >> 33 RBC confirmed by by microscopy microscopy of RBC // hpf hpf Hematuria Hematuria Hematuria Additional Additional Characterization Characterization

Gross (grossly visible) or microscopic? Gross (grossly visible) or microscopic? Gross Gross more more likely likely significant significant IfIf gross, gross, is is itit initial initial (urethra), (urethra), terminal terminal (bladder (bladder neck neck or or prostate), prostate), or or total total (interior (interior of of bladder bladder or or upper upper tract) tract) Hematuria

Evaluation Evaluation 1: 1: Examine Examine Urine Urine In if >> 11 squamous In women, women, get get cath. cath. UA UA if squamous cell cell // hpf hpf (vaginal contamination) (vaginal contamination) Is color red but Is color red but dipstick dipstick -- ?? Consider Consider phenolphthalein, rhodamine B, phenolphthalein, rhodamine B, others others Is dipstick + but no RBC Is dipstick + but no RBC present?

present? Beware Beware ifif specific 1.008 (RBC specific gravity gravity << 1.008 (RBC may may have have been there, but lysed) been there, but lysed) Usually Usually false false positive positive test test Unfortunately, referral Unfortunately, aa common common referral Hematuria

Evaluation Evaluation 1: 1: Examine Examine Urine Urine Is Is there there pyuria pyuria or or bacteruria? bacteruria? Probable Probable infection infection (any (any GU GU site) site) Is Is there there proteinuria proteinuria (> (> 22 ++ on on dipstick), dipstick),

or or are are there there dysmorphic dysmorphic RBCs RBCs or or RBC RBC casts? casts? Probable Probable glomerulonephritis glomerulonephritis Hematuria Evaluation Evaluation 2: 2: History History and and Physical Physical Flank Flank Pain Pain Stone Stone

Dysuria, Dysuria, bladder bladder irritability irritability Bladder Bladder or or prostate prostate infection infection Sickle Sickle cell, cell, diabetes diabetes Papillary Papillary necrosis necrosis Family Family or or personal personal history history of

of calculi, calculi, PCKD, PCKD, other other GU GU // Neph Neph diseases diseases Possible Possible familial familial trait trait Hematuria Evaluation Evaluation 2: History and Physical Trauma, Trauma, or or intense intense physical physical activity activity May May be be cause cause of of hematuria

hematuria Tobacco Tobacco use, use, occupational occupational chemical chemical exposure exposure (aromatic (aromatic dyes) dyes) Risk Risk for for renal renal and and urothelial urothelial cancers cancers Hematuria Evaluation Evaluation 2: 2: History History and and Physical Physical

Visible Visible blood blood at at urethral urethral meatus meatus Urethral Urethral source source Fever, Fever, CVAT CVAT Pyelonephritis Pyelonephritis Prostate Prostate exam exam Prostatitis, Prostatitis, Prostate Prostate cancer cancer Pelvic Exam Pelvic Exam

Urethral, Urethral, vaginal, vaginal, or or labial labial lesions lesions Hematuria Evaluation Evaluation 3: 3: Labs Labs and and Procedures Procedures Formal Formal urinalysis urinalysis with with microscopic microscopic examination examination Urine Urine culture culture

IfIf infection is DOCUMENTED, omit rest infection is DOCUMENTED, then then can can omit rest of if hematuria hematuria clears clears with with antibiotics antibiotics of work-up work-up if IVU IVU versus versus KUB KUB ++ US US versus versus CT CT +/+/- Urine Urine cytology cytology +/+/- Serum

Serum electrolytes electrolytes and and creatinine creatinine Cystoscopy Cystoscopy Hematuria Diagnostic Diagnostic Categories Categories Infection Infection Calculi Calculi Cancer Cancer Benign neoplasms / lesions Benign neoplasms / lesions Other obstruction Other obstruction Trauma / exertional hematuria Trauma / exertional hematuria

Medical renal disease Medical renal disease Blood dyscrasia Blood dyscrasia // anticoagulation anticoagulation Benign familial hematuria Benign familial hematuria Hematuria Infection Infection Kidney Kidney Pyelonephritis - parenchyma Pyelonephritis - parenchyma Pyonephrosis - pus in collecting Pyonephrosis - pus in collecting system system Renal abscess - pus pocket in Renal abscess - pus pocket in parenchyma

parenchyma Hematuria Infection Infection Bladder Bladder Bacterial cystitis Bacterial cystitis Prostate Prostate Bacterial prostatitis Bacterial prostatitis Urethra Urethra Infectious urethritis Infectious urethritis Hematuria Calculi Calculi Kidney Kidney

Obstructive vs. Non-obstructive Obstructive vs. Non-obstructive Simple vs. Staghorn Simple vs. Staghorn Ureter Ureter Obstructive vs. Non-obstructive Obstructive vs. Non-obstructive Bladder Bladder Hematuria Cancer Cancer Kidney Kidney Renal Renal cell cell carcinoma, carcinoma, other other Upper Upper collecting collecting system system

Urothelial, Urothelial, other other Bladder Bladder Urothelial, Urothelial, other other Urethra Urethra Squamous Squamous cell, cell, other other Prostate Prostate Adenocarcinoma, Adenocarcinoma, other other Hematuria Benign Benign Neoplasms Neoplasms // Lesions

Lesions Kidney Kidney Simple Simple cysts cysts Cystic Cystic renal renal diseases diseases Angiomyolipoma, Angiomyolipoma, other other neoplasms neoplasms Ureter Ureter Hemangioma, Hemangioma, other other Bladder Bladder Endometrioma, Endometrioma, other other Urethra

Urethra Condyloma, Condyloma, other other Hematuria Other Other Obstructions Obstructions Ureter Ureter Ureteropelvic Ureteropelvic junction junction (UPJ) (UPJ) Intrinsic Intrinsic strictures strictures Extrinsic Extrinsic obstruction obstruction Bladder Bladder Bladder Bladder outlet

outlet obstruction obstruction (BOO) (BOO) Benign Benign prostatic prostatic hyperplasia hyperplasia (BPH) (BPH) Other Other Urethra Urethra Strictures, Strictures, other other Hematuria Trauma Trauma // Exertional Exertional Hematuria Hematuria Cannot Cannot be be assumed assumed to to be

be cause cause Medical Medical Renal Renal Disease Disease Previous Previous Nephrology Nephrology lecture lecture Blood Blood Dyscrasia Dyscrasia // Anticoagulation Anticoagulation Cannot Cannot be be assumed assumed to to be be cause cause Benign Benign Familial Familial Hematuria

Hematuria Microscopic only, negative negative work-up Microscopic only, work-up Kidney & Upper Urinary Tract Kidney, Kidney, Intra-renal Intra-renal Collecting Collecting System, System, and and Ureter Ureter Topics Topics covered covered (case (case presentations) presentations) Ureteral obstruction (UPJO) Ureteral obstruction (UPJO) Calculi (ureteral, renal)

Calculi (ureteral, renal) Infection (pyelonephritis) Infection (pyelonephritis) Cancer (renal cell carcinoma) Cancer (renal cell carcinoma) Renal cystic disease (ADPKD) Renal cystic disease (ADPKD) Kidney & Upper Urinary Tract: Obstruction Case Case 1: 1: Ureteropelvic Ureteropelvic Junction Junction Obstruction Obstruction (UPJO) (UPJO) 24 24 year year old old woman woman Long history of intermittent left flank pain, Long history of intermittent left flank pain, recently recently worsening worsening

Not during sleep Not during sleep Especially Especially notices notices after after fluid fluid intake, intake, or or even even more more after after drinking drinking alcohol alcohol No significant medical history No significant medical history Kidney & Upper Urinary Tract: Obstruction Case Case 1: 1: Ureteropelvic Ureteropelvic Junction Junction Obstruction Obstruction (UPJO)

(UPJO) Young Young age age -- diagnosed diagnosed mostly mostly in in children, children, variable variable after after that that Intermittent symptoms - typical of adult Intermittent symptoms - typical of adult presentation presentation Pain increased Pain increased with with fluid fluid intake intake Classic Classic for for UPJO UPJO Flow-dependent obstruction (like a slow Flow-dependent obstruction (like a slow but

but not-yet not-yet clogged clogged drain) drain) Kidney & Upper Urinary Tract: Obstruction Anatomy Anatomy of of Kidney Kidney and and Upper Upper Urinary Urinary Tract Tract Paired Paired Kidneys Kidneys Urine from collecting tubules that terminate Urine from collecting tubules that terminate in in papillae papillae drain drain into: into: Calyces, that coalesce into Calyces, that coalesce into

Infundibula, Infundibula, which which drain drain into into Renal Pelvis Renal Pelvis Travels Travels down down ureter ureter (peristalsis) (peristalsis) Kidney & Upper Urinary Tract: Obstruction Calyx Infundibulum J.S. Wolf Renal Pelvis Kidney & Upper Urinary Tract: Obstruction

Anatomy Anatomy of of Kidney Kidney and and Upper Upper Urinary Urinary Tract Tract Tight Tight spots spots prone prone to to obstruction obstruction Ureteropelvic junction (UPJ) Ureteropelvic junction (UPJ) Mid-ureter Mid-ureter as as crosses crosses iliac iliac vessels vessels (over (over sacrum sacrum on on plain plain radiograph)

radiograph) Ureterovesical junction (UVJ) Ureterovesical junction (UVJ) Of Of these, these, the the UPJ UPJ most most common common site site of of congenital congenital obstruction obstruction Grays Anatomy Grays Anatomy Image removed Kidney & Upper Urinary Tract: Obstruction Case Case 1:

1: Ureteropelvic Ureteropelvic Junction Junction Obstruction Obstruction (UPJO) (UPJO) Evaluation Evaluation Intravenous Intravenous urogram urogram Unilateral hydronephrosis and non-visualization of Unilateral hydronephrosis and non-visualization of ureter ureter Diuretic renal scintigraphy Diuretic renal scintigraphy 50% 50% split split renal renal function function T 1/2 (time for to exit

T 1/2 (time for of of tracer tracer to exit kidney) kidney) on on symptomatic 100 minutes symptomatic side side >> 100 minutes (normal (normal << 10 10 minutes) minutes) Intravenous Urogram Left Left hydronephrosis hydronephrosis and and nonnonvisualization visualization of of the the ureter

ureter Source Undetermined Diuretic Renal Scintigraphy Source Undetermined Excretion Excretion from from left left kidney kidney is is delayed delayed Kidney & Upper Urinary Tract: Obstruction Case Case 1: 1: Ureteropelvic Ureteropelvic Junction Junction Obstruction Obstruction (UPJO) (UPJO) Treatment Treatment Percutaneous Percutaneous endopyelotomy endopyelotomy

A A minimally-invasive minimally-invasive alternative alternative to to formal formal pyeloplasty pyeloplasty Nephro-ureteral Nephro-ureteral stent stent capped capped off off in in 11 week, week, and and removed removed in in 66 weeks weeks Complete Complete resolution resolution

Kidney & Upper Urinary Tract: Obstruction Causes Causes of of UPJO UPJO Primary Primary Histological disorganization Histological disorganization excess excess longitudinal longitudinal muscle muscle fibers fibers (loss (loss of of normal normal organization) organization) increase increase in in collagen collagen attenuation attenuation of of muscle muscle bundles bundles Crossing vessels, high insertion, kinks,

bands Crossing vessels, high insertion, kinks, bands Secondary Secondary Traumatic scar, iatrogenic scar, external Traumatic scar, iatrogenic scar, external compression compression (think (think cancer!) cancer!) Kidney & Upper Urinary Tract: Obstruction Evaluation Evaluation of of UPJO UPJO Determine Determine presence presence and and degree degree of of obstruction obstruction

Is there obstruction, or just dilation? Is there obstruction, or just dilation? Complete Complete or or partial partial obstruction? obstruction? Determine renal function Determine renal function IfIf kidney kidney not not working working well, well, may may be be little little value value in in repairing repairing Determine cause of obstruction Determine cause of obstruction Kidney & Upper Urinary Tract: Obstruction

Dilation Dilation of of the the Urinary Urinary Tract Tract Non-obstructive Non-obstructive Ureteral Ureteral reflux, reflux, prior prior obstruction, obstruction, extra-renal extra-renal pelvis, pelvis, diuresis diuresis Stagnation Stagnation may may lead lead to but to infection infection and and calculi, calculi, but usually usually innocuous innocuous Obstructive

Obstructive Increased Increased resistance resistance to to urine urine flow flow that that produces produces increased increased proximal proximal pressure subsequent loss pressure and and subsequent loss of of organ organ function function Occasionally Occasionally difficult difficult to to distinguish distinguish from from non-obstructive non-obstructive Massive Vesico-ureteral Reflux on Cystogram

Source Undetermined Kidney & Upper Urinary Tract: Obstruction Evaluation Evaluation of of UPJO UPJO Anatomic Anatomic tests tests Intravenous urography Intravenous urography Renal (surface) ultrasonography Renal (surface) ultrasonography Computed tomography Computed tomography Endoluminal ultrasonography Endoluminal ultrasonography Functional tests Functional tests Ultrasonography with resistive indices Ultrasonography with resistive indices Diuretic renal scintigraphy Diuretic renal scintigraphy

Whitaker test Whitaker test Intravenous Urography Normal Normal kidney kidney Hydronephrosis Hydronephrosis Source Undetermined Renal Ultrasonography Source Undetermined Hydronephrosis Hydronephrosis Computed Tomography Can Can determine determine additional additional anatomy, anatomy, including including vessels vessels crossing

crossing at at UPJ UPJ Source Undetermined Computed Tomography Can Can determine determine additional additional anatomy, anatomy, including including vessels vessels crossing crossing at at UPJ UPJ Source Undetermined Endoluminal Ultrasonography Can Can detect detect vessels vessels crossing crossing over over UPJ, UPJ, but but requires requires retrograde retrograde catheterization

catheterization Source Undetermined Ultrasonography with Resistive Indices (PSV - LDV) /PSV: Normal Diastolic Diastolic flow flow velocity velocity is is preserved preserved Source Undetermined Ultrasonography with Resistive Indices (PSV - LDV) /PSV: Obstructed Source Undetermined As As resistance resistance to to blood blood flow flow increases, increases, diastolic diastolic flow flow velocity velocity decreases, decreases, and and

resistive resistive index index increases increases (R.I. (R.I. >> 0.70) 0.70) Diuretic Renal Scintigraphy: most definitive non-invasive test T T == Time Time for for of of radiotracer radiotracer to to be be excreted excreted from from kidney kidney after after furosemide furosemide T T == 55 minutes minutes (normal (normal << 10 10 min.)

min.) Sources Undetermined T T == 25 25 minutes minutes (obstructed (obstructed >> 15 15 min.) min.) Whitaker Test: most definitive test Pressure Pressure in in renal renal pelvis pelvis at at set set infusion infusion rate rate through through nephrostomy nephrostomy tube tube (> (> 15 15 mmHg mmHg at at 15 15 cc/min

cc/min infusion infusion == obstruction) obstruction) Source Undetermined Kidney & Upper Urinary Tract: Obstruction Treatment Treatment of of UPJO UPJO Open Open pyeloplasty pyeloplasty Laparoscopic Laparoscopic pyeloplasty pyeloplasty Percutaneous Percutaneous endopyelotomy endopyelotomy

Most Invasive / Most Effective Retrograde Retrograde balloon balloon dilation dilation Retrograde endopyelotomy Retrograde endopyelotomy Acucise (cutting balloon) endopyelotomy Acucise (cutting balloon) endopyelotomy Least Invasive / Least Effective Break Kidney & Upper Urinary Tract: Calculi Case Case 2: 2: Acutely Acutely Obstructing Obstructing Distal Distal Ureteral Ureteral Calculus Calculus

30 30 year year old old man man Sudden Sudden onset onset of of right right flank flank pain pain Initial Initial gross gross hematuria, hematuria, but but now now clear clear No No fevers fevers and and chills, chills, but but nausea nausea Frequent Frequent urination urination

Pain Pain somewhat somewhat less less after after aa few few hours hours Restless, Restless, moving moving about about Right Right flank, flank, lower lower quadrant, quadrant, and and testicular testicular pain pain // tenderness tenderness 5 5 -- 10 10 RBC RBC // hpf hpf on on urinalysis urinalysis

Kidney & Upper Urinary Tract: Calculi Case Case 2: 2: Acutely Acutely Obstructing Obstructing Distal Distal Ureteral Ureteral Calculus Calculus Sudden Sudden onset c/w renal renal colic colic onset pain pain -- c/w Urine Urine cleared suggests obstruction cleared -- suggests obstruction Nausea Nausea -- very renal colic very common common with with renal colic

Freq. Freq. urination by distal distal calculi urination -- irritation irritation by calculi Pain Pain decreased decreased -- forniceal forniceal rupture, rupture, decrease decrease in in pressure pressure from from renal renal hemodynamics hemodynamics Moving Moving about about -- NOT NOT peritonitis peritonitis Flank Flank to to scrotum scrotum -- expected expected radiation

radiation Urinalysis Urinalysis -- RBCs in 85% 85% RBCs in Kidney & Upper Urinary Tract: Calculi Suspected Suspected Acute Acute Ureteral Ureteral Obstruction Obstruction Differential Differential Diagnosis Diagnosis Intrinsic Intrinsic Calculi, tumor, Calculi, tumor, clot, clot, edema edema Extrinsic Extrinsic Compression by tumor, lymph node Compression by tumor, lymph node

Acute versus acute-on-chronic Acute versus acute-on-chronic Calculi, or partially-obstructing Calculi, or calculi calculi impacted impacted into into partially-obstructing stricture? stricture? Clot, or clot on tumor? Clot, or clot on tumor? Kidney & Upper Urinary Tract: Calculi Suspected Suspected Acute Acute Ureteral Ureteral Obstruction Obstruction Radiographic Radiographic Evaluation Evaluation KUB urography KUB and and Intravenous Intravenous urography

Anatomic picture, localize pathology Anatomic picture, localize pathology Ultrasonography Ultrasonography CT CT Non-contrast Non-contrast (stones) (stones) CT urogram (with contrast, like IVU) CT urogram (with contrast, like IVU) Retrograde Retrograde pyelography pyelography Injection through catheter Injection through catheter Intravenous Urography This This stone

stone is is less less dense dense than than contrast contrast material, material, so so appears appears as as filling filling defect defect Source Undetermined Intravenous Urography This This stone stone is is faintly faintly radioradioopaque opaque

Source Undetermined Intravenous Urography and and is is easier easier to to identify identify when when contrast contrast material material comes comes down down to to it it Source Undetermined Kidney & Upper Urinary Tract: Calculi Spontaneous Spontaneous Passage Passage of of Ureteral Ureteral

Stones Width Width 44 mm mm Proximal Proximal 20% 20% Middle Middle 45% 45% Distal Distal 55% 55% 55 mm mm 66 mm mm 6% 6% 0% 0% 30% 30%

10% 10% 45% 45% 25% 25% 100% 50% 0% 1 J.S. Wolf 2 3 4 5 6 7 8 9 10 Ultrasonography

Hydronephrosis Hydronephrosis Source Undetermined Computed Tomography Source Undetermined (almost) (almost) all all stones stones dense dense on on CT CT Computed Tomography Source Undetermined Secondary Secondary signs signs of of ureteral ureteral obstruction obstruction Computed Tomography Source Undetermined

Secondary Secondary signs signs of of ureteral ureteral obstruction obstruction Computed Urography Source Undetermined Intravenous Urography Irregular Irregular Filling Filling Defect Defect Source Undetermined Kidney & Upper Urinary Tract: Calculi If If filling filling defect defect on on contrast contrast study study Neoplasm

Neoplasm Urothelial Urothelial neoplasm neoplasm most most common common Blood Blood clot clot Will Will resolve resolve during during follow-up follow-up Radio-lucent Radio-lucent calculus calculus (15%) (15%) Other Other 85% 85% are are calcium calcium containing containing Refers Refers to

to appearance appearance on on plain plain film film (all (all typical typical stones stones are are opaque opaque on on CT CT scan) scan) Radio-lucent Radio-lucent stones stones are are usually usually uric uric acid acid (only (only medically medically dissolvable dissolvable stone) stone) Need Need to to rule-out rule-out tumor! tumor!

Kidney & Upper Urinary Tract: Calculi Case Case 3: 3: Non-obstructing Non-obstructing Renal Renal Calculus Calculus 65 65 year year old old man man Microscopic hematuria Microscopic hematuria Remote history of urolithiasis Remote history of urolithiasis Mild Mild prostatism prostatism Unremarkable PE except for prostatic Unremarkable PE except for prostatic enlargement enlargement

Urinalysis - 10 RBC / hpf Urinalysis - 10 RBC / hpf Plain Radiography Densely Densely radioradioopaque opaque stones stones Source Undetermined Kidney & Upper Urinary Tract: Calculi Indications Indications for for Surgical Surgical Treatment Treatment of of Urolithiasis Urolithiasis Urinary infection Urinary tract tract infection

Significant obstruction Significant obstruction Pain refractory to oral medication Pain refractory to oral medication Others Others Staghorn calculi - risk of urosepsis Staghorn calculi - risk of urosepsis Long-standing ureteral calculi - eventual Long-standing ureteral calculi - eventual obstruction obstruction Occupational or lifestyle reasons Occupational or lifestyle reasons Plain Radiography Staghorn Staghorn Calculus Calculus Source Undetermined Kidney & Upper Urinary Tract: Calculi

Surgical Surgical Treatment Treatment of of Urolithiasis Urolithiasis Open laparoscopic Open surgical surgical // laparoscopic lithotomy lithotomy Percutaneous Percutaneous nephrostolithotomy nephrostolithotomy endoscopy) endoscopy) Ureteroscopy Ureteroscopy (Retrograde (Retrograde endoscopy) endoscopy)

Extracorporeal Extracorporeal shock shock wave wave lithotripsy lithotripsy (SWL) (SWL) Most Invasive / Most (Antegrade (Antegrade Effective Least Invasive / Least Effective Source Undetermined Source Undetermined Image removed Source Undetermined Source Undetermined Source Undetermined

Kidney & Upper Urinary Tract: Calculi Parameters Parameters Determining Determining Treatment Treatment of Urolithiasis Size Size Location Location Composition Composition Medical Condition, Patient Preference, Medical Condition, Patient Preference, Physician Physician Preference Preference Kidney & Upper Urinary Tract: Calculi Size Size

Small Small SWL SWL Moderate Moderate Ureteroscopy Ureteroscopy Large Large Percutaneous nephrostolithotomy Percutaneous nephrostolithotomy Kidney & Upper Urinary Tract: Calculi Location Location Distal

Distal Ureter Ureter Scope > SWL Scope > SWL Middle Middle Ureter Ureter Scope > SWL Scope > SWL Proximal Proximal Ureter Ureter SWL > Scope ? SWL > Scope ? Kidney Kidney SWL SWL >> Scope

Scope Computed Tomography Source Undetermined Distal Distal aspect aspect of of UVJ, UVJ, almost almost in in bladder bladder Computed Tomography Source Undetermined Huge Huge bilateral bilateral renal renal calculi calculi Kidney & Upper Urinary Tract: Calculi Composition Composition Dense Dense (Calcium (Calcium oxalate oxalate monohydrate)

monohydrate) Scope Scope Fuzzy/ Faint (Calcium oxalate dihydrate, calcium Fuzzy/ Faint (Calcium oxalate dihydrate, calcium phosphate, phosphate, struvite) struvite) SWL SWL Cystine Cystine Scope Scope Uric Acid Uric Acid SWL SWL Plain Radiography Densely Densely

radioradioopaque opaque stone stone Source Undetermined Plain Radiography Fuzzy Fuzzy radioradioopaque opaque stone stone Source Undetermined Kidney & Upper Urinary Tract: Pyelonephritis Case Case 4: 4: Pyelonephritis Pyelonephritis 29 old woman 29 year year old woman Started with of dysuria urination), Started with 33 days

days of dysuria (painful (painful urination), urinary frequency // urgency urgency urinary frequency Now temp 101.7 C, right flank pain Now temp 101.7 C, right flank pain History History Occ previous UTI Occ previous UTI Recently married Recently married Limited sexual activity before marriage, now active Limited sexual activity before marriage, now active PE - Right CVAT PE - Right CVAT Kidney & Upper Urinary Tract: Pyelonephritis Case Case 4: 4: Pyelonephritis Pyelonephritis

Young Young woman woman -- UTI UTI is is common common Initial cystitis (infection ascends) common and Initial cystitis (infection ascends) common and suggest UTI suggest UTI Systemic Systemic symptoms symptoms -- distinguishes distinguishes upper upper from from lower lower tract UTI tract UTI Previous UTI - helps establish her characteristic Previous UTI - helps establish her characteristic symptoms UTI symptoms of of UTI Sexual Sexual activity

activity -- predisposing predisposing factor factor for for UTI UTI in in women women CVAT - renal involvement CVAT - renal involvement Kidney & Upper Urinary Tract: Pyelonephritis Acute Acute Pyelonephritis Pyelonephritis Most Most common common disease disease of of the the kidney kidney Usually ascending infection Usually ascending infection Diagnosis by clinical findings and urine Diagnosis by clinical findings and urine culture culture

(85% (85% are E. Coli) Coli) are GNR; GNR; E. Imaging Imaging used to detect used to detect complications complications or or to to assess assess for for predisposing predisposing factors factors Complications: papillary necrosis, pyonephrosis, Complications: papillary necrosis, pyonephrosis, abscess, abscess, sepsis sepsis Predisposing Predisposing factors: factors: obstruction, obstruction, calculi, calculi, vesicovesicoureteral

ureteral reflux reflux Source Undetermined Lobar Lobar Nephronia Nephronia Kidney & Upper Urinary Tract: Pyelonephritis Management Management of of Acute Acute Pyelonephritis Pyelonephritis Typical Typical case case -- fever fever resolves resolves within within 48 48 hrs hrs of of starting starting antibiotics antibiotics Oral abx in most Oral abx in most

Intravenous abx if very Intravenous abx if very ill-appearing ill-appearing Debilitated patients at greater Debilitated patients at greater risk risk Diabetes mellitus Diabetes mellitus Steroids Steroids Chronically ill Chronically ill Immuno-suppressed Immuno-suppressed Kidney & Upper Urinary Tract: Pyelonephritis Management Management of of Acute Acute Pyelonephritis Pyelonephritis History History of

of complications complications or or lack lack of of response response to to antibiotics antibiotics US US or or CT CT for for obstruction, obstruction, calculi calculi Upper Upper tract tract obstruction obstruction with with infection infection DRAINAGE DRAINAGE (stent, (stent, percutaneous percutaneous tube) tube) Upper Upper tract tract calculus

calculus with with infection infection Treat Treat acute acute infection, infection, then then calculus calculus If If child child or or recurrent recurrent US US for for scars scars Voiding Voiding cystogram cystogram for for reflux reflux Kidney & Upper Urinary Tract: Pyelonephritis Drainage

Drainage procedures procedures Percutaneous Percutaneous nephrostomy nephrostomy tube tube Image of a percutaneous nephrostomy tube removed Ureteral Ureteral stent stent Hildpeyi, wikimedia commons Break Kidney & Upper Urinary Tract: Masses & Cysts Case Case 5: 5: Renal Renal Cell Cell Carcinoma

Carcinoma (RCC) (RCC) 64 64 year year old old man man Gross hematuria Gross hematuria Flank pain Flank pain History History 66 pack-year smoker 66 pack-year smoker PE PE Fullness in right flank Fullness in right flank Kidney & Upper Urinary Tract: Masses & Cysts Case Case 5: 5: Renal

Renal Cell Cell Carcinoma Carcinoma (RCC) (RCC) Older Older man man -- peak peak in in 66thth decade, decade, 3:1 3:1 M:F M:F overall overall Hematuria - most common presenting Hematuria - most common presenting sign sign Flank pain and flank mass - along with Flank pain and flank mass - along with hematuria, hematuria, the the classic classic triad triad Smoking - major acquired risk factor Smoking - major acquired risk factor

Kidney & Upper Urinary Tract: Masses & Cysts Demographics Demographics of of RCC RCC Incidence: Incidence: 12.8 12.8 per per 100,000 100,000 (00 (00 -- 04) 04) Mortality: 4.2 per 100,000 (00 - 04) Mortality: 4.2 per 100,000 (00 - 04) estimated estimated 51,190 51,190 new new cases cases in in 2007 2007 (~2% (~2% of of adult adult malignancies) malignancies) estimated 12,890 deaths in 2007

estimated 12,890 deaths in 2007 Lifetime Lifetime Risk Risk (M (M // F) F) Risk of occurrence - 1.71 / 1.01 % Risk of occurrence - 1.71 / 1.01 % Risk of death - 0.59 / 0.35 % Risk of death - 0.59 / 0.35 % SEER Cancer Statistics Kidney & Upper Urinary Tract: Masses & Cysts Risk Risk factors factors for for RCC RCC Cigarettes Cigarettes Obesity Obesity

Hypertension Hypertension Occupational exposures Occupational exposures Dialysis Dialysis Hereditary Hereditary von Hippel-Lindau disease von Hippel-Lindau disease Tuberous Sclerosis Tuberous Sclerosis Kidney & Upper Urinary Tract: Masses & Cysts Pathology Pathology of of RCC RCC Proximal

Proximal tubular tubular cell cell neoplasm neoplasm Often venous involvement Often venous involvement Hemorrhagic, Hemorrhagic, necrotic, necrotic, cystic, cystic, and and calcified calcified components components common common Metastasize most commonly to Metastasize most commonly to lung, lung, liver, liver, bone, bone, adrenal, adrenal, and and contralateral contralateral kidney kidney

Kidney & Upper Urinary Tract: Masses & Cysts Common Common Renal Renal Tumors Tumors Pathology Pathology Malignant? Malignant? Relative Relative % % Renal Renal Cell Cell Ca. Ca. Yes Yes 85% 85% Urothelial Urothelial Ca. Ca. Yes

Yes 5% 5% Oncocytoma Oncocytoma No No 5% 5% Most Most not not 5% 5% Other Other Kidney & Upper Urinary Tract: Masses & Cysts Histology Histology Most Most Renal

Renal Cell Cell Carcinomas Carcinomas have have Clear Clear cell cell histology histology Lipids Lipids (dissolve (dissolve out out during during slide slide processing) processing) and and glycogen glycogen Fuhrman Fuhrman grading grading (1 (1 to to 4) 4) 1 1

== well well differentiated differentiated 4 4 == poorly poorly differentiated differentiated Kidney & Upper Urinary Tract: Masses & Cysts Genetics Genetics Most Most renal renal cell cell carcinomas carcinomas are are sporadic sporadic Are associated with several syndromes, Are associated with several syndromes, the the most most common common of of which which is is VonVonHippel

Hippel Lindau Lindau syndrome syndrome Autosomal dominant Autosomal dominant Cerebellar and retinal vascular tumors Cerebellar and retinal vascular tumors Adrenal and renal tumors (inc cysts) Adrenal and renal tumors (inc cysts) Kidney & Upper Urinary Tract: Masses & Cysts Genetics Genetics Von-Hippel Von-Hippel Lindau Lindau syndrome syndrome Autosomal dominant Autosomal dominant Mutation in VHL tumor suppressor gene: Mutation in VHL tumor suppressor gene: 3p25-26 3p25-26 95% of sporadic clear cell renal cell

95% of sporadic clear cell renal cell carcinomas carcinomas have have VHL VHL mutation mutation One of the strongest associations among One of the strongest associations among solid solid tumors tumors Opportunities for gene therapy Opportunities for gene therapy Kidney & Upper Urinary Tract: Masses & Cysts Symptoms Symptoms // Signs Signs of of RCC RCC Hematuria Hematuria (29 (29 60%) 60%)

Flank Flank pain pain (14 (14 51%) 51%) Flank Flank mass mass (21 (21 47%) 47%) All 3 = Classic triad All 3 = Classic triad Present Present Usually Usually in in << 10% 10% signifies signifies advanced

advanced disease disease Kidney & Upper Urinary Tract: Masses & Cysts Paraneoplastic Paraneoplastic Syndromes Syndromes ESR ESR elevation elevation Calcium elevation Calcium elevation Polycythemia Polycythemia Anemia Anemia Thrombophlebitis Thrombophlebitis Hyperinsulinism Hyperinsulinism

LFT LFT elevation elevation Kidney & Upper Urinary Tract: Masses & Cysts Central Central Role of Imaging Simple Cyst Indeterminate Cyst Solid Mass Benign ? Malignant Kidney & Upper Urinary Tract: Masses & Cysts Stage Stage Migration Migration of of RCC RCC due due to to more more frequent frequent imaging

imaging 1970s 1970s 4% 4% of of RCC RCC << 33 cm cm 32% 32% presented presented with with metastases metastases 1980s 1980s 25 25 -- 40% 40% were were incidental incidental finding finding 25% 25% of of RCC RCC << 33 cm cm 17%

17% presented presented with with metastases metastases 1990s 1990s 60% 60% were were incidental incidental finding finding Kidney & Upper Urinary Tract: Masses & Cysts Imaging Imaging Modalities Intravenous Intravenous Urography Urography (IVU, (IVU, IVP) IVP) Ultrasonography

Ultrasonography (US) (US) Computed Computed Tomography Tomography (CT) (CT) Magnetic Magnetic Resonance Resonance Imaging Imaging (MRI) (MRI) Kidney & Upper Urinary Tract: Masses & Cysts Intravenous Intravenous Urography Urography Typical Typical upper upper tract tract imaging imaging for for hematuria hematuria work-up

work-up Excellent visualization of collecting system Excellent visualization of collecting system Renal Renal mass mass or or cyst cyst causes causes displacement displacement of of surrounding surrounding organ organ or or deformation deformation of of outline outline Screening study only Screening study only IfIf renal renal mass

mass // cyst cyst suspected, suspected, further further imaging imaging is is required required Intravenous Urography Mass Mass Effect Effect in in kidney kidney Source Undetermined Kidney & Upper Urinary Tract: Masses & Cysts Ultrasonography Ultrasonography Usual IVU suspicious Usual follow-up follow-up to to IVU suspicious for for renal renal mass

mass // cyst cyst No ionizing radiation No ionizing radiation Non-invasive Non-invasive Operator dependent Operator dependent Reliably (85% of Reliably identifies identifies simple simple cyst cyst (85% of renal renal mass mass // cysts) cysts) If NOT a simple If NOT a simple cyst cyst

Cross-sectional Cross-sectional imaging imaging Ultrasonography Simple Simple Cyst Cyst Source Undetermined Kidney & Upper Urinary Tract: Masses & Cysts Sonographic Sonographic Characteristics Characteristics Anechoic Anechoic with with enhanced enhanced through through transmission transmission Simple Simple cyst cyst

Echogenic Echogenic with with acoustic acoustic shadowing shadowing Stone Stone or or other other calcification calcification Iso Iso // hypoechoic hypoechoic mass mass Solid Solid mass mass Ultrasonography Renal Renal Stone Stone Source Undetermined

Ultrasonography Nodule Nodule in in Cyst Cyst Source Undetermined Ultrasonography Source Undetermined Solid Solid Mass Mass Kidney & Upper Urinary Tract: Masses & Cysts Computed Computed Tomography Tomography Current Current gold gold standard standard Non-contrast scan, then scan with intravenous Non-contrast scan, then scan with intravenous contrast contrast Enhancement = Hounsfield units (density) Enhancement = Hounsfield units (density)

increase increase by by >> 10 10 with with contrast contrast 3 to 5 mm maximum cut width 3 to 5 mm maximum cut width Spiral CT - single breath hold Spiral CT - single breath hold Minimize motion artifact Minimize motion artifact Exact duplication of cuts Exact duplication of cuts Computed Tomography Source Undetermined Simple Simple Cyst Cyst Computed Tomography Source Undetermined

Complex Complex Cyst Cyst Source Undetermined Renal Renal Cell Cell Carcinoma Carcinoma Kidney & Upper Urinary Tract: Masses & Cysts Solid, Solid, Enhancing Enhancing Renal Renal Mass Mass on on CT CT is is RCC RCC until until Proven Proven Otherwise Otherwise Other Other possibilities possibilities

Oncocytoma Oncocytoma Benign, Benign, but but indistinguishable indistinguishable from from RCC RCC on on imaging imaging Angiomyolipoma Angiomyolipoma Benign, Benign, but but can can bleed bleed ifif large large Usually Usually diagnosed diagnosed by by imaging imaging fat fat Inflammatory Inflammatory mass mass History History of of febrile febrile illness

illness Lymphoma Lymphoma Malignant, Malignant, but but no no surgery surgery Source Undetermined Oncocytoma Oncocytoma ?? Angiomyolipoma Angiomyolipoma Source Undetermined Renal Renal Abscess Abscess Source Undetermined Renal Renal Lymphoma Lymphoma Source Undetermined Kidney & Upper Urinary Tract: Masses & Cysts

Magnetic Magnetic Resonance Resonance Imaging Imaging Currently Currently no no advantage advantage over over CT CT except except in in certain certain situations situations Allergy to contrast material Allergy to contrast material Elevated Elevated creatinine creatinine Distinguish wall in some cysts Distinguish wall in some cysts Detection of venous tumor thrombus in Detection of venous tumor thrombus in RCC RCC (has (has replaced

replaced invasive invasive venography) venography) Magnetic Resonance Imaging Source Undetermined Thick Thick Cyst Cyst Wall Wall Magnetic Resonance Imaging Tumor Tumor Thrombus Thrombus in in Vena Vena Cava Cava Source Undetermined Kidney & Upper Urinary Tract: Masses & Cysts

Sensitivity Sensitivity for for Diagnosis Diagnosis of of RCC RCC << 33 cm cm Intravenous Intravenous urography urography -- 67% 67% Ultrasonography Ultrasonography -- 79% 79% Computed Computed tomography tomography

-- 94% 94% Kidney & Upper Urinary Tract: Masses & Cysts Evaluation Evaluation of of Suspected Suspected RCC RCC Initial Initial imaging imaging study study (often (often IVU IVU or or US, US, either either incidentally incidentally or or for for workup workup of of hematuria hematuria or or other other signs signs // symptoms) symptoms)

CT or MRI for local assessment CT or MRI for local assessment Define Define lesion lesion Assess nodes, vein, other organs Assess nodes, vein, other organs Staging Staging CXR, CXR, Bloods, Bloods, ++ Bone Bone Scan Scan and and others others Kidney & Upper Urinary Tract: Masses & Cysts Staging Staging and and Management

Management of of RCC RCC Stage Stage II Tumor < 7 cm limited to kidney (T1) Tumor < 7 cm limited to kidney (T1) no LN+ or metastases no LN+ or metastases Radical Radical or or Partial Partial Nephrectomy Nephrectomy Stage II Stage II Tumor Tumor >> 77 cm cm limited limited to to kidney kidney (T2) (T2)

No LN+ or metastases No LN+ or metastases Radical Radical Nephrectomy Nephrectomy Kidney & Upper Urinary Tract: Masses & Cysts Staging Staging and and Management Management of of RCC RCC Stage Stage III III Tumor into vein, fat, or adrenal Tumor into vein, fat, or adrenal Or one single LN+ Or one single LN+

Radical Radical Nephrectomy Nephrectomy Stage IV Stage IV Tumor Tumor Or > 1 Or > 1 beyond beyond LN+ LN+ Or Or Gerotas Gerotas fascia fascia (T4) (T4) metastases metastases

Systemic Systemic Therapy Therapy (Chemo, (Chemo, Immuno) Immuno) Kidney & Upper Urinary Tract: Masses & Cysts Prognosis Prognosis of RCC Stage Stage II Stage II Stage II Stage III Stage III Stage Stage IV IV 55 year year survival survival ~90%

~90% ~80% ~80% ~40 ~40 -- 60% 60% ~10% ~10% Kidney & Upper Urinary Tract: Masses & Cysts Case Case 6: 6: Autosomal Autosomal Dominant Dominant Polycystic Polycystic Kidney Kidney Disease Disease (ADPKD) (ADPKD) 37 37 year year old old woman woman No recent medical care No recent medical care Left flank fullness Left flank fullness

Adopted, unknown family history Adopted, unknown family history PE PE Mass in left flank Mass in left flank BP 170/100 BP 170/100 Kidney & Upper Urinary Tract: Masses & Cysts Case Case 6: 6: Autosomal Autosomal Dominant Dominant Polycystic Polycystic Kidney Kidney Disease Disease (ADPKD) (ADPKD) Middle-aged Middle-aged -- usually usually diagnosed diagnosed in in third third decade

decade Fullness - HUGE bilateral cysts, Fullness - HUGE bilateral cysts, symptomatic symptomatic in in ~15% ~15% Over 50% have family history Over 50% have family history Hypertension - almost always, given enough Hypertension - almost always, given enough time time Kidney & Upper Urinary Tract: Masses & Cysts ADPKD ADPKD Autosomal Autosomal dominant dominant inheritance inheritance 85% 85% from from PKD1 PKD1 mutation

mutation (16q13) (16q13) 15% (4q21-23 15% from from PKD2 PKD2 mutation mutation (4q21-23) (4q21-23) (4q21-23 Virtually Virtually 100% 100% penetrance penetrance Incidence Incidence 11 // 1000 1000 live live births

births 6000 6000 new new cases cases annually annually Prevalence Prevalence ~~ 200,000 200,000 Kidney & Upper Urinary Tract: Masses & Cysts ADPKD ADPKD Epithelial renal Epithelial proliferation proliferation in in renal renal tube

tube renal tubule tubule become as become cyst cyst as cyst cyst grows grows itit compresses compresses renal renal parenchyma parenchyma << 1% 1% tubules tubules become become cysts cysts Also Also hepatic, hepatic, pancreatic pancreatic and and splenic splenic cysts,

cysts, and and cerebral cerebral aneurysms aneurysms Hypertension Hypertension Renal Renal failure failure -- most most but but not not all, all, usually usually in in 55thth decade decade ADPKD ADPKD Source Undetermined Source Undetermined

Kidney & Upper Urinary Tract: Masses & Cysts Other Other Cystic Cystic Diseases Diseases of of the the Kidney Kidney Simple Simple cysts cysts In In population population over over age age 50 50 50% 50% pathologically, pathologically, 33% 33% by by CT CT Single Single or or multiple multiple

Simple Simple cyst cyst complicated complicated by by hemorrhage hemorrhage or or infection infection (Complex (Complex cyst) cyst) Acquired Acquired cystic cystic kidney kidney disease disease (ACKD) (ACKD) 40% 40% of of dialysis dialysis patients patients by by 33 years years Controversial Controversial increase increase in in RCC

RCC ACKD ACKD Source Undetermined Kidney & Upper Urinary Tract: Masses & Cysts Evaluation Evaluation of of Renal Renal Cysts Cysts Simple Simple cysts cysts definable definable with with US US No further work-up needed No further work-up needed ADPKD, ACKD ADPKD, ACKD Definable by history and PE Definable by history and PE Complex Cyst

Complex Cyst Simple cyst complicated by infection or Simple cyst complicated by infection or hemorrhage hemorrhage Cystic renal cancer Cystic renal cancer Diagnostic dilemma, surgery often required Diagnostic dilemma, surgery often required Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide Slide 28: 28: Stuart Stuart Wolf Wolf Slide 30: Grays Slide 30: Grays Anatomy Anatomy Slide Slide 31: 31: Grays Grays Anatomy Anatomy Slide

34: Source Slide 34: Source Undetermined Undetermined Slide Slide 35: 35: Source Source Undetermined Undetermined Slide Slide 40: 40: Source Source Undetermined Undetermined Slide Slide 42: 42: Source Source Undetermined Undetermined Slide 43: Source Undetermined Slide 43: Source Undetermined Slide Slide 44: 44: Source Source Undetermined Undetermined Slide 45: Source Undetermined

Slide 45: Source Undetermined Slide Slide 46: 46: Source Source Undetermined Undetermined Slide Slide 47: 47: Source Source Undetermined Undetermined Slide Slide 48: 48: Source Source Undetermined Undetermined Slide 49: Source Undetermined Slide 49: Source Undetermined Slide Slide 50: 50: Source Source Undetermined Undetermined Slide 57: Source Undetermined Slide 57: Source Undetermined Slide Slide 58:

58: Source Source Undetermined Undetermined Slide Slide 59: 59: Source Source Undetermined Undetermined Slide Slide 60: 60: Stuart Stuart Wolf Wolf Slide 61: Source Slide 61: Source Undetermined Undetermined Slide Slide 62: 62: Source Source Undetermined Undetermined Slide 63: Source Undetermined Slide 63: Source Undetermined Slide Slide 64: 64: Source Source Undetermined Undetermined

Slide Slide 65: 65: Source Source Undetermined Undetermined Slide Slide 66: 66: Source Source Undetermined Undetermined Slide 69: Source Undetermined Slide 69: Source Undetermined Slide Slide 71: 71: Source Source Undetermined Undetermined Slide Slide 73: 73: Source Source Undetermined Undetermined Slide Slide 74: 74: Source Source Undetermined Undetermined Slide Slide 76:

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Slide Slide 90: 90: Source Source Undetermined Undetermined Slide Slide 93: 93: Hildpeyi, Hildpeyi, Wikimedia Wikimedia Commons, Commons, http://commons.wikimedia.org/wiki/File:Ureteral_stent.jpg, http://commons.wikimedia.org/wiki/File:Ureteral_stent.jpg, CC:BY-SA, CC:BY-SA, http://creativecommons.org/licenses/by-sa/3.0/deed.en http://creativecommons.org/licenses/by-sa/3.0/deed.en Slide Slide 110: 110: Source Source Undetermined Undetermined Slide Slide 112: 112: Source Source Undetermined Undetermined Slide Slide 114: 114: Source Source Undetermined Undetermined Slide Slide 115: 115: Source

Source Undetermined Undetermined Slide Slide 116: 116: Source Source Undetermined Undetermined Slide Slide 118: 118: Source Source Undetermined Undetermined Slide 119: Source Undetermined Slide 119: Source Undetermined Slide Slide 120: 120: Source Source Undetermined Undetermined Slide 122: Source Undetermined Slide 122: Source Undetermined Slide Slide 123: 123: Source Source Undetermined Undetermined Slide

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