Urology/Nephrology

1. Urology/Nephrology Lecture Three—March 6th, 2012

2. Interstitial Cystitis

3. Interstitial Cystitis • “Painful Bladder Syndrome” • Diagnosis of Exclusion • Negative culture and cystology • No other obvious cause (radiation, chemical, vaginitis, herpes, urethral diverticulum) • 18-40 people per 100,000 • Affects both genders but most patients are women • Higher prevalence in white and Jewish • average age 40 years • Bladder problems in childhood • Up to 50% spontaneous remission (average 8 months)

4. Interstitial Cystitis • Etiology unknown • Most likely several diseases with similar symptoms • Multiple theories as to possible cause • Increased epithelial permeability • sensory nervous system abnormalities • autoimmunity • Associated with severe allergies, IBS, IBD

5. Signs and Symptoms • Pain with bladder filling, relieved by urination • Urgency, frequency, nocturia • Labs – urinalysis, urine culture, urine cytology, urodynamic testing • Cystoscopy – distend bladder with fluid (hydrodistention) • Glomerulations (submucosal hemorrhage) • Hunner’s Ulcers • Thinned bladder epithelium • Differential Diagnosis – radiation, chemical, bacterial cystitis, herpes, vaginitis, bladder carcinoma, eosinophillic cystitis, tuberculous cystitis, urethral diverticulum, urethral carcinoma

9. Treatment • No cure – goal is symptomatic relief • Hydrodistention – done as part of work-up – 20-30% see improvement • Oral medications • Amitryptyline (10-75 mg/day orally) • Nifedipine (30-60 mg/day orally) and other CCBs • Elmiron (100 mg 3x/day orally) – helps restore integrity to bladder epithelium • Intravesical instillation of DMSO and heparin • TENS units • Acupuncture • Surgery – last resort—cystourethrectomy

10. Phimosis / Paraphimosis

11. Phimosis / Paraphimosis • Phimosis – inability to retract the distal foreskin over the glans penis • Physiologic – occurs naturally in newborn males • Pathologic – inability to retract foreskin when it was previously retractable or after puberty • Paraphimosis – foreskin cannot be pulled back over the head of the penis – uncircumcised or partially circumcised males

13. Risk Factors • Phimosis – Poor hygiene, recurrent inflammation or infection of glans or foreskin, forceful retraction of foreskin, elderly • Patients with phimosis are at risk for developing paraphimosis when the foreskin is forcibly retracted past the glans and/or the patient or caretaker forgets to replace the foreskin after retraction. • Penile piercings increase the risk of developing paraphimosis • Impairment of venous/lymphatic flow to the glans leads to venous engorgement and worsening swelling  arterial supply is compromised  penile infarction/necrosis, gangrene

14. Phimosis - Signs and Symptoms • Physiologic – inability to retract the foreskin during routine cleaning or bathing; "ballooning" of the prepuce during urination • Pathologic– painful erections, hematuria, recurrent UTIs, preputial pain, weakened urinary stream • The foreskin cannot be retracted proximally over the glans penis. • Physiologic – preputialorifice is unscarred and healthy appearing. • Pathologic – contracted white fibrous ring may be visible around the preputial orifice

15. Phimosis

16. Paraphimosis – Signs and Symptoms • Painful, swollen glans penis • Uncircumcised or partially circumcised patient • Foreskin retracted behind glans penis and cannot be replaced to its normal position • Tight, restricting ring around the glans • Flaccidity of penile shaft proximal to constriction • Glans – initially its normal pink hue and soft, becomes increasingly erythematous/edematous, becomes firm and blue or black with necrosis • Preverbal infant may present only with irritability or may be an incidental finding in a debilitated patient.

17. Paraphimosis

18. Treatment • Phimosis – rarely require emergency intervention – outpatient urology referral • Paraphimosis– urologic emergency – immediate intervention with goal of reducing foreskin to naturally occuring position over the glans penis • Manual reduction • Osmotic reduction • Puncture reduction • Hyaluronidase method • Aspiration • Vertical incision • Surgery (emergency circumcision)

19. Treatment

20. Treatment

21. Bladder Carcinoma

22. Bladder Carcinoma • 2nd most common urologic cancer • 2.7 : 1 male-to-female; average age at diagnosis – 65 • Risk factors – cigarette smoking and industrial dye/solvent • 98% are epithelial malignancies • 90% - urothelial cell carcinomas • 7% - squamous cell cancers • 2% - adenocarcinomas

23. Bladder Carcinoma • Hematuria is presenting symptom in 85-90% • Irritative voiding (frequency and urgency) • Many with no symptoms at all • Abdominal masses – if large or deeply infiltrating • Hepatomegaly or lymphadenopathy (if metastasis) • Lymphedema of lower extremities – if locally advanced or metastasis to pelvic lymph nodes

24. Bladder Carcinoma • Urinalysis – microscopic or gross hematuria, pyuria • Azotemia may be present on labs • Cytology – 80-90% sensitive in detecting higher grade/stage cancers but less so in superficial or well-differentiated lesions (50%) • Anemia—chronic blood loss or metastasis to marrow • Urinary tumor markers – under investigation • Imaging – Ultrasound, CT, or MRI may show filling defects • Cystourethroscopy/Biopsy – cystoscopy confirms diagnosis; pt then undergoes transurethral resection and random biopsies • Grading (cellular features) and staging (wall penetration and metastasis)

26. Treatment • Superficial – (Ta, T1) – complete transurethral resection and intravesical chemotherapy • Invasive, Localized – (T2, T3) – risk of nodal metastases and progression – radical cystectomy, radiation, or combination of chemotherapy and selective surgery or radiation • Muscle invasive (T2 or greater) transitional cell carcinoma requires systemic chemotherapy • READ – Specific forms of treatment (p. 1592)

27. Prognosis • Initially, 50-80% are superficial (Ta, Tis, T1) • With proper treatment, metastasis/progression are low and survival is excellent (81%) • T2, T3 – 5 year survival ranges from 50-75% • Long-term survival for pts with metastasis at initial presentation is rare

28. Testicular Cancer

29. Testicular Cancer • 2-3 new cases per 100,000 males in US each year • 90-95% of primary testicular tumors are germ cell tumors • Nonseminomas – mixed cell types (40%) embryonal cell carcinoma (20%), teratoma (5%), choriocarcinoma (<1%) • Seminomas – 35% • Non-germinal neoplasms • 5% of testicular tumors occur in pts with history of cryptorchidism but 15-10% of these occur in normal testis • Testicular cancer is slightly more common on right than left

30. Testicular Cancer • Painless enlargement of the testis • Sensations of heaviness • Acute testicular pain 2ointratesticular hemorrhage – 10% • Asymptomatic – 10% • Metatstatic symptoms – 10% (back pain, cough, lower extremity edema) • Discrete mass or diffuse testicular enlargement • Secondary hydrocele – 5-10% • Supraclaviuclaradenopathy • Abdominal mass • Gynecomastia – 5% (germ cell tumors)

31. Testicular Cancer • Labs – hCG, α-fetoprofen, LDH • Liver transaminases (metastasis) or anemia • Imaging – scrotal ultrasound (extratesticular / intratesticular) • Diagnosis – confirmed by inguinal orchectomy • Staging – chest/abdominal/pelvic CT scanning • Nonseminomas – Stage A – confined to testicle; Stage B – retroperitoneal lymph node involvement; Stage C – distant metastasis • Seminomas – Stage I – confined to testicle; Stage II – retroperitoneal lymph node involvement

32. Testicular Cancer • Initial Intervention – inguinal exploration with early vascular control of spermatic cord structures • Examine testis for cancer – if unable to exclude cancer, radical orchiectomy • 75% of stage I nonseminomas are cured by orchiectomy alone • Stage I and II a/b seminomas – radical orchiectomy and retroperitoneal irradiation • IIc and Stage III seminomas – chemotherapy

33. Testicular Cancer • Surveillance – monthly for first 2 years after diagnosis/treatment then bimonthly for 3rd year • tumor markers at each visit • CXR/CT scans every 3 months • 80% of relapses in first 2 years • Nonseminoma prognosis – stage A with 96-100% 5 yr survival rate, stage B with 90% disease-free survival 5 yrs • Stage I seminoma – 98%, Stage IIa seminomas – 92-94% • Stage III seminoma – 95% • Disseminated disease – 55-80%

34. Prostate Cancer

35. Prostate Cancer • Most common noncutaneous cancer in US men • 2nd most common cause of cancer-related death • 218,000 new cases/yr and 27,000 deaths/yr • Clinical incidence does not equal prevalence on autopsy • Over 40% of men over 50 y/o have prostatic carcinoma • Incidence increases with age • Autopsy prevalence is similar world-wide, but clinical incidence varies and is high in North America/Europe, intermediate in South America, low in Far East • Black race, + family history, high dietary fat intake

36. Prostate Cancer

37. Prostate Cancer • Most are associated with palpably normal prostates and detected solely by elevated PSA • May have focal nodules or indurated areas on DRE • Urinary retention or neurologic symptoms – epidural metastasis and cord compression • Obstructive voiding – usually due to BPH, but large or locally extensive prostatic cancers may cause • Lower extremity edema – lymph node metastasis • Back pain or pathologic fractures – skeletal metastasis • Axial skeleton – most common site of metastasis

38. Prostate Cancer • PSA – glycoprotein made only by prostate cells (benign or malignant) – corresponds with prostate volume • 10-15% of men will have elevated PSA on screening • 18-30% of men with PSA 4.1-10 will have prostate cancer • 50-70% of pts with PSA > 10 will have cancer • If not treated, PSA level correlates with volume and stage of disease • Organ confined – usually PSA <10 • Advanced disease (seminal vesicle invasion, lymph node involvement, occult metastases) – PSA >40 • 98% of pts with metastatic cancer have elevated PSA • 20% of pts who undergo radical prostatectomy have normal PSA • Rising PSA after therapy = progressive disease • PSA increase of over 0.75 ng/mL per year is suspicious

39. Prostate Cancer • PSA – glycoprotein made only by prostate cells (benign or malignant) – corresponds with prostate volume • 10-15% of men will have elevated PSA on screening • 18-30% of men with PSA 4.1-10 will have prostate cancer • 50-70% of pts with PSA > 10 will have cancer • If not treated, PSA level correlates with volume and stage of disease • Organ confined – usually PSA <10 • Advanced disease (seminal vesicle invasion, lymph node involvement, occult metastases) – PSA >40 • 98% of pts with metastatic cancer have elevated PSA • 20% of pts who undergo radical prostatectomy have normal PSA • Rising PSA after therapy = progressive disease • PSA increase of over 0.75 ng/mL per year is suspicious

40. Prostate Cancer • Urinary retention/urethral obstruction – BUN/CR elevation • Bony metastasis – alkaline phosphatase, calcium • DIC (disseminated intravascular coagulation) – advanced • Biopsy – transrectal ultrasound guided biopsy • Spring-loaded 18-gauge biopsy needle • Transrectal US – staging (hypoechoic areas) • MRI – evaluate prostate and lymph nodes • Radionuclide bone scan – superior to plain skeletal films • Most metastases are multiple and usually in axial skeleton • Advanced local lesion, metastasis symptoms, high grade disease, PSA >20 • FNA (lymphadenopathy), plain films (bone scan) • CT is of limited use

41. Prostate Cancer • DRE alone – 1.5 - 7%, usually advanced cancers • Transrectal US – not appropriate for screening; expensive, low specificity (high biopsy) • PSA combined with DRE – increased detection rate • Serial PSA – increases specificity (>0.75 ng/yr increase is increased likelihood of cancer) • PSA density – in normal DRE and transrectal US – serum PSA divided by volume of the prostate • Free serum PSA vs. protein-bound (lower free PSA = increased odds of cancer) • Benefit of screening for prostate cancer is controversial

42. Prostate Cancer • Localized—active surveillance is an option, but pts with life expectancy > 10 years should get treatment – radiation vs. radical prostatectomy • Radical Prostatectomy – seminal vesicles, prostate, ampulla of vas deferens removed • Modern surgery – usually preserves urinary continence and may also preserve erectile function • Healthy patients with T1 and T2 cancers are ideal candidates • Advanced – rarely candidates for prostatectomy alone • Radiation – external beam or implantation of radioisotopes • Surveillance – older pts with small volume, well-differentiated cancers

43. Prostate Cancer • Cryosurgery – less invasive, positive biopsy rate 7-23% • Metastatic – death is almost invariably due to uncontrolled metastatic disease • Most prostate carcinomas are androgen-dependent and 70-80% of metastatic disease will respond to androgen deprivation (table 39-7) • Prognosis – varies with stage, grade of cancer, PSA level, number and extent of + biopsies • Tables 39-8 and 39-9

44. Questions?