Advanced Pathophysiology Unit 7: Renal-Urologic Page 1 of 6

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1 Advanced Pathophysiology Unit 7: Renal-Urologic Page 1 of 6 Learning Objectives for this File: 1. Understand how clinical presentation drives the diagnostic workup 2. Recognize how patient education is part of management

2 Advanced Pathophysiology Unit 7: Renal-Urologic Page 2 of 6 CASE STUDY: A 79 yo man with PAINLESS GROSS hematuria INITIAL PRESENTATION: (CC, HPI, FH/SH) a 79 yo man presented to his primary care provider with a complaint of 2 episodes of painless gross hematuria. He states that the first episode occurred 10 months ago, and the most recent episode occurred 2 weeks ago. He feels fine, but his wife insisted that he come in for evaluation. PMH: HTN x 20 years, poorly controlled on beta-blockers. SH: 35 pack year smoking history, social drinker. FH: noncontributory. PE: VS BP 200/100 P 80 RR 15 T 99 F. Gen: WDWN WM NAD. Positive findings include enlarged prostate (smooth, nontender, 3+ size) on digital rectal exam. INITIAL EVALUATION (WORKUP): Chemistry profile: Elevated: Total cholesterol 254. Normal: all others U/A: ph 6.0, sg 1.035, amber, hazy. Dip & micro positive: 3+ protein, WBC 19/hpf (0-5), RBC 49/hpf (0-4), hyaline cast 10/lpf (neg). CBC: normal WBC, H/H, differential, RBC indices and platelet count. Tumor markers: PSA 3.4 (0-4) Intravenous pyelogram (IVP): irregular 2 cm filling defect in left bladder consistent with tumor or blood clot (dye outlines the lumen of the GU tract, but there is an area that does not show the dye filling defect) (the contrast dye looks white). FILLING DEFECT (black area that doesn t fill with contrast dye)

3 Advanced Pathophysiology Unit 7: Renal-Urologic Page 3 of 6 DIAGNOSIS: OBSTRUCTIVE UROPATHY Benign Prostatic Hypertropy (BPH) and anything else?? Clinicians divide renal/urologic disease into three categories: o pre-renal (usually dehydration or other cause of poor renal perfusion) o intrinsic renal (glomerular or tubular disease) o post-renal (obstructive uropathy) -- lesions INSIDE the ureters, bladder, urethra (renal stone, BPH, bladder tumor) -- or pushing in from the OUTSIDE (ovarian cancer, abdominal abscess) Labwork varies usually as follows: o pre-renal: elevated BUN, Cr probably OK o intrinsic renal: Cr elevated more than BUN would suggest o post-renal: initially all may be normal, until renal obstruction affects outflow and glomerular/tubular function from pressure effects

4 Advanced Pathophysiology Unit 7: Renal-Urologic Page 4 of 6 PATHOPHYSIOLOGIC CORRELATES OF INITIAL PRESENTATION: Painless hematuria is most often associated with bladder cancer. Other findings in this patient include obvious cardiac risk factors (uncontrolled HTN, dyslipidemia). CLINICAL COURSE: He underwent surgical procedures of TURP (transurethral resection prostate) for BPH With endoscopic biopsy of a solid mass in the bladder wall. Urine for cytology (Papanicolaou stain): o hyperchromatic, pleomorphic cells with high nuclear/cytoplasmic ratio. o Consistent with high-grade transitional cell bladder carcinoma. o Some inflammatory cells are also seen. He was discharged from home on the third day, no pathology available yet. Told to return to the office for final results. Trans-urethral resection of the Prostate (TURP) Bladder Biopsy Note: at this point, the provider should have given this pt. more information about his probable diagnosis to ensure proper followup.

5 Advanced Pathophysiology Unit 7: Renal-Urologic Page 5 of 6 LABORATORY RESULTS: Bladder wall biopsy: thickened mucosa with mitotic figures (suspicious for neoplasm) DNA histogram of urine: DNA peaks reflect the mitosis phase of the cells, indicating rapidly dividing cells consistent with transitional cell carcinoma. Urine Cytology -- Uroepithelial Cells: PAP test of the urine. Normal Bladder cancer -- hyperchromatic nuclei, enlarged cells

6 Advanced Pathophysiology Unit 7: Renal-Urologic Page 6 of 6 FINAL CASE SUMMARY: The space occupying lesion in the bladder proved to be transitional cell carcinoma with invasion. He will need oncologic f/u for evaluation of possible metastasis. His smoking put him at risk for bladder cancer. FINAL THOUGHTS: Prevention: Newer information also indicates that (for men at least) increased regular fluid intake will reduce rate of eventually developing bladder cancer. Risk factors: o Occupational: aniline dye workers o Lifestyle: smoking, analgesic abuse and analgesic nephropathy are associated with this cancer. o Gender: male:female = 3:1 o Prior chemotherapy: cyclophosphamide may induce this cancer. o Smoking: Freedman ND, et al. JAMA 17 Aug 2011;306(7):737. At: Pathology: these cancers arise from one clonal cell, and are often recurrent. Provider concerns: o patients dismiss GROSS PAINLESS HEMATURIA, especially if only occurring only once or twice why? There isn t any PAIN!! o any gross painless hematuria is bladder cancer, until proven otherwise!! o aggressive workup is warranted for early detection; this cancer, if detected early, has an excellent chance for remission and 5-year survival rate. o If detected after bladder wall invasion, statistics are not hopeful. o Even in cases of low-grade cancers and non-invasive pathology, annual or semi-annual f/u is required (cystoscopy, urine cytology) to r/o recurrence (lifetime followup). THE FINAL FINAL THOUGHTS: all painless gross hematuria presentations require aggressive w/u to definitively rule out bladder cancer (males & females) all patients with any prior cancer are at risk of future cancers (high index of suspicion) all patients with prior chemotherapy or radiation therapy are ALSO at risk of future cancers PS remember the word gross in clinical usage means visible to the naked eye (as opposed to microscopic hematuria, which is only found on microscopic or reagent lab analysis)