To explain why image-guided biopsy of upper urinary tract urothelial cell carcinoma (UUTUCC) found by CT urography is recommended before surgery.

Transcription

1 An innovative technique for image-guided biopsy of upper urinary tract urothelial cell carcinoma detected by CT urography for histopathological confirmation of diagnosis and elimination of false-positive results Poster No.: C-1820 Congress: ECR 2012 Type: Educational Exhibit Authors: T. N. H. Matin, D. M. L. Tse, N. C. Cowan; Oxford/UK Keywords: Urinary Tract / Bladder, CT, Fluoroscopy, Biopsy, Pyelography, Diagnostic procedure, Pathology, Neoplasia DOI: /ecr2012/C-1820 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 51

2 Learning objectives To explain why image-guided biopsy of upper urinary tract urothelial cell carcinoma (UUTUCC) found by CT urography is recommended before surgery. To illustrate common CT urography false-positive findings for UUT-UCC. To report a new innovative technique for image-guided biopsy of UUT-UCC detected by CT urography for histopathological confirmation of diagnosis and elimination of falsepositive results. Page 2 of 51

3 Background UUT-UCC accounts for 5-7% of all urothelial tumors (1). UUT-UCC occurs four times more frequently within the renal pelvis than the ureter. Bilateral renal pelvis UUT-UCC is found in 1-5%; patients with a primary bladder urothelial cell carcinoma may have UUTUCC in 3% of cases, whereas 30-40% of UUT-UCC cases are associated with a bladder tumor (2). Risk factors for UUT-UCC include: Cigarette smoking Occupational exposure to chemicals or dyes, benzenes or aromatic amines Increasing age (> 40 years) History of urological disorder or disease, irritative voiding symptoms or urinary tract infection resistant to antibiotic treatment Analgesic abuse (e.g. phenacetin) History of pelvic irradiation or cyclophosphamide therapy. UUT-UCC occurs most commonly in male patients above the age of 40, with a peak incidence between the sixth and seventh decades (3). Hematuria is the presenting symptom in patients with renal pelvic or ureteric tumors in over 75% of cases. Until recently, consensus regarding the most appropriate imaging modality for investigation of patients with hematuria had not been achieved. Traditionally, intravenous urography (IVU) (4) and ultrasound (5) were the modalities of choice. However, IVU is relatively poor at detecting UUT-UCC, failing to detect up to 40% of tumors (6-8). By definition, CT urography includes at least one excretory phase series and therefore presents an ideal method for examining the urothelium. CT urography is now accepted as the first-line investigation for hematuria in patients at high-risk for UUT-UCC. CT urography is superior to both ultrasound and IVU (9, 10) with high diagnostic accuracy for detection of UUT-UCC reported in several studies (11-16). The high sensitivity (88%-100%) and specificity (93%-100%) of CT urography for evaluation of patients with hematuria is corroborated by a recent meta-analysis (17). The principal disadvantages of CT urography are: Reader error False positive diagnoses Increased radiation dose. Page 3 of 51

4 Unfortunately, discussion of all CT urography disadvantages is beyond the scope of this educational exhibit. The most common false positive CT urography diagnoses mimicking UUT-UCC will be highlighted. Furthermore, an innovative technique for image-guided biopsy to eliminate false positive CT urography results will be described. Page 4 of 51

5 Imaging findings OR Procedure details CT Urography false positive diagnoses for UUT-UCC The optimal patient pathway would involve arranging curative surgery directly following positive diagnosis of UUT-UCC made on CT urography. Unfortunately this is not a realistic approach given the low positive predictive value of CT urography for UUT-UCC, which ranges from (11, 12, 14, 15). This low positive predictive value may be explained by false positive diagnoses mimicking UUT-UCC. The most common false positive CT urography diagnoses are highlighted in [Table 1] (Fig. 1-17). Histopathological confirmation of UUT-UCC is therefore recommended before surgery, to ensure surgery is only performed for patients with malignant disease (18). 1. Clot (Fig. 1 on page 10 Fig. 2 on page 10 Fig. 3 on page 11 Fig. 4 on page 12) 2. Debris 3. Kink of the ureter, accentuated by inspiration (Fig. 5 on page 13 Fig. 6 on page 14 Fig. 7 on page 15 Fig. 8 on page 16 Fig. 9 on page 17) 4. Fibroepithelial polyp 5. Injury to the ureter following passage of a stone, stent placement or ureteroscopy, inflammation, fibrosis. 6. Ureteritis cystica (Fig. 10 on page 18 Fig. 11 on page 19) 7. Flow artefacts following furosemide administration or layering effects 8. Unusual looking papilla, a normal variant 9. Amyloid (Fig. 12 on page 20 Fig. 13 on page 21 Fig. 14 on page 22 Fig. 15 on page 23) 10. Nephrogenic adenoma 11 Renal cell carcinoma 12 Lymphoma Page 5 of 51

6 13 Vascular impressions (Fig. 16 on page 24 Fig. 17 on page 25) [Table 1] CT urography false positive diagnoses for upper urinary tract urothelial cell carcinoma. Innovative image-guided biopsy technique for UUT-UUC (FBx) The clinical cohort consisted of a consecutive series of 140 patients, aged above 40 years old, presenting with macroscopic hematuria to the hematuria clinic. Infection was excluded prior to imaging. All patients were initially investigated with CT urography. In cases where CT urography was equivocal or suspicious for UUT-UCC, patients underwent retrograde ureteropyelography (RUP) and a new and innovative technique for fluoroscopic-guided biopsy (FBx) (Fig. 18 on page 26 Fig. 19 on page 27 Fig. 20 on page 28 Fig. 21 on page 29). The diagnostic accuracy of RUP for detecting UUT-UCC was calculated. Histopathology from surgery/ureteroscopy/fbx and a combination of clinical/imaging/histopathology follow-up constituted the reference standard. Procedure details (Fig. 22 on page 30 Fig. 23 on page 31 Fig. 24 on page 32 Fig. 25 on page 33) Procedures were performed by radiologists in the interventional radiology suite using C-arm fluoroscopy under sedoanalgesia. A flexible cystoscope was used to catheterize the ureteric orifice and retrograde ureteropyelography performed to identify the tumor. A 7F semi-rigid sheath was placed into the ureter and via a 6F guide-catheter, using ureteroscopic biopsy forceps, samples were obtained and sent for histopathological analysis. Results RUP was performed in 133 patients including 94 males and 39 females (age range years old). No reference standard was established in 27 cases, which were subsequently excluded from analysis. RUP was positive for UUT-UCC in 82 cases (Fig. 26 on page 34 Fig. 27 on page 35 Fig. 28 on page 36 Fig. 29 on page 37 Fig. 30 on page 38 Fig. 31 on page 39 Fig. 32 on page 40 Fig. 33 on page 41 Fig. 34 on page 42 Fig. 35 on page 43 Fig. 36 on page 44) and normal in 24. There were 8 technical failures due to non-visualization of the ureteric orifice and touch bleeding. These cases were classified as RUP positive since clinically the patients were treated to have a positive result requiring further investigation. The diagnostic accuracy Page 6 of 51

7 of RUP for UUT-UCC detection was calculated using the 2 x 2 table constructed below [Tables 2, 3]. Disease Positive Disease Negative RUP Positive RUP Negative 1 23 [Table 2] 2 x 2 table for the 106 patients with established reference standard that underwent RUP. Sensitivity (%) Specificity (%) Positive Negative predictive value predictive value (%) (%) RUP [Table 4] Sensitivity, Specificity, PPV and NPV for RUP Of the 86 RUP positive cases (including those with and without a reference standard), 84 proceeded to undergo the new fluoroscopic-guided biopsy technique. There were two exclusions: Anticoagulation with warfarin (n=1) Biopsy technically not feasible (n=1). The results from FBx are shown in (Fig. 37 on page 45 Fig. 38 on page 46). The new fluoroscopic-guided biopsy technique exhibits high technical success rate and good correlation between grade of biopsy and resected specimen. Page 7 of 51

8 Fig. 37: FBx positive results and correlation between grade of FBx and resected specimen. References: Radiology, Oxford University, The Churchill Hospital - Oxford/UK Page 8 of 51

9 Fig. 38: FBx negative results. References: Radiology, Oxford University, The Churchill Hospital - Oxford/UK No complications were observed with the new fluoroscopic-guided biopsy technique. Furthermore, the new technique obviates the need for ureteroscopic-guided biopsy, which requires general anaesthesia. Page 9 of 51

10 Images for this section: Fig. 1: Case 1: Axial unenhanced CT urography demonstrating a soft tissue mass lesion in the right renal lower pole calyx. Page 10 of 51

11 Fig. 2: Case 1: Axial excretory phase CT urography showing enhancement of the soft tissue mass lesion in the right kidney from 33 HU to 98 HU, suggestive of UUT-UCC. Page 11 of 51

12 Fig. 3: Case 1: Coronal excretory phase CT Urography from same patient showing the right lower pole mass lesion. Page 12 of 51

13 Fig. 4: Case 1: Retrograde ureteropyelography of the right upper urinary tract was normal; the CT Urography abnormality most likely representing a clot. Page 13 of 51

14 Fig. 5: Case 2: Axial excretory phase CT urography showing apparent filling defect of left ureter. Page 14 of 51

15 Fig. 6: Case 2: Selected image from retrograde ureteropyelography confirming the CT urography abnormality to correspond to a ureteric kink. Page 15 of 51

16 Fig. 7: Case 2: Selected image from retrograde ureteropyelography confirming the CT urography abnormality to correspond to a ureteric kink. Page 16 of 51

17 Fig. 8: Case 2: Axial excretory phase CT urography from same patient showing a short unopacified segment of the right pelvic ureter. Page 17 of 51

18 Fig. 9: Case 2: Retrograde pyelography confirming normal right upper tract. Page 18 of 51

19 Fig. 10: Case 3: Axial excretory phase CT urography showing apparent filling defect associated with left pelvic ureter. Page 19 of 51

20 Fig. 11: Case 3: Retrograde ureteropyelography showing characteristic appearance of ureteritis cystica rather than UUT-UCC. Page 20 of 51

21 Fig. 12: Case 4: Axial excretory phase CT Urography image from a 59 year old man who presented with loin pain and macroscopic hematuria showing thickening of the left pelvic-ureter junction. Page 21 of 51

22 Fig. 13: Case 4: Coronal excretory phase CT Urography image also showing thickening of the left pelvic-ureter junction. Ureteroscopy and fluoroscopic guided biopsies were negative on several occasions. Page 22 of 51

23 Fig. 14: Case 4: Follow-up axial excretory phase CT Urography demonstrating disease progression. Page 23 of 51

24 Fig. 15: Case 4: Retrograde ureteropyelography confirming an abnormality in the left lower pole, which was subsequently biopsied. Biopsy results showed amyloid and no evidence of malignancy. Page 24 of 51

25 Fig. 16: Case 5: Coronal excretory phase MIP CT urography showing filling defect of right pelvic ureter, suspicious for UUT-UCC. Page 25 of 51

26 Fig. 17: Case 5: Selected image from retrograde ureteropyelography confirming normal right upper urinary tract. The CT urography abnormality was most likely due to vascular calcification. Page 26 of 51

27 Fig. 18: Case 6: Axial excretory phase CT urography showing a filling defect in the collecting system of the left upper pole. Page 27 of 51

28 Fig. 19: Case 6: Coronal excretory phase CT urography showing a filling defect in the collecting system of the left upper pole. Page 28 of 51

29 Fig. 20: Case 6: Selected image from retrograde ureteropyelography showing heterogeneous mass lesion associated with left upper pole collecting system. Page 29 of 51

30 Fig. 21: Case 6: Selected image from fluoroscopic-guided biopsy, which confirmed UUTUCC. Page 30 of 51

31 Fig. 22: Case 7: Selected image from new and innovative technique for fluoroscopicguided biopsy of suspected UUT-UCC. The large right upper pole lesion was confirmed as UUT-UCC on biopsy. Page 31 of 51

32 Fig. 23: Case 7: Selected images from new and innovative technique for fluoroscopicguided biopsy of suspected UUT-UCC. The large right upper pole lesion was confirmed as UUT-UCC on biopsy. Page 32 of 51

33 Fig. 24: Case 7: Selected images from new and innovative technique for fluoroscopicguided biopsy of suspected UUT-UCC. The large right upper pole lesion was confirmed as UUT-UCC on biopsy. Page 33 of 51

34 Fig. 25: Case 7: Selected images from new and innovative technique for fluoroscopicguided biopsy of suspected UUT-UCC. The large right upper pole lesion was confirmed as UUT-UCC on biopsy. Page 34 of 51

35 Fig. 26: Case 8: Axial excretory phase CT urography demonstrating circumferential filling defect of right ureter and unopacified left ureter. Page 35 of 51

36 Fig. 27: Case 8: Coronal excretory phase CT urography demonstrating circumferential filling defect of right ureter. Page 36 of 51

37 Fig. 28: Case 8: Coronal excretory phase CT urography demonstrating circumferential filling defect of right ureter. Page 37 of 51

38 Fig. 29: Case 8: Selected image from retrograde ureteropyelography showing an "applecore" lesion of the mid right ureter. Page 38 of 51

39 Fig. 30: Case 8: Selected image from retrograde ureteropyelography showing goblet or Bergman sign of the left lower ureter. Biopsies from both ureters confirmed bilateral UUTUCC. Page 39 of 51

40 Fig. 31: Case 9: Axial excretory phase CT urography showing filling defect in lower left pelvic ureter. Page 40 of 51

41 Fig. 32: Case 9: Coronal excretory phase CT urography showing heterogeneous filling defect in lower left pelvic ureter. Page 41 of 51

42 Fig. 33: Case 9: Retrograde ureteropyelography confirms abnormality of left lower ureter. Subsequent fluoroscopic-guided biopsy yielded good samples showing UUT-UCC. Page 42 of 51

43 Fig. 34: Case 10: Selected image from retrograde ureteropyelography showing goblet or Bergman sign of the right lower ureter. Page 43 of 51

44 Fig. 35: Case 10: Selected image from retrograde ureteropyelography showing unopacified segment of lower right ureter with associated hydronephrosis and hydroureter. Page 44 of 51

45 Fig. 36: Case 10: Selected image from fluoroscopic-guided biopsy of obstructing right lower ureteric lesion. Biopsy showed UUT-UCC. Page 45 of 51

46 Fig. 37: FBx positive results and correlation between grade of FBx and resected specimen. Page 46 of 51

47 Fig. 38: FBx negative results. Page 47 of 51

48 Conclusion CT urography false-positive findings for UUT-UCC may be eliminated by accurate image interpretation and a new and innovative image-guided biopsy technique for radiologists, providing histopathological confirmation of diagnosis. Page 48 of 51

49 Personal Information T. N. H. Matin, D. M. L. Tse, N. C. Cowan Department of Radiology The Churchill Hospital Oxford University Hospitals NHS Trust Old Road Headington Oxford United Kingdom OX3 7LJ Page 49 of 51

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51 13. Fritz GA, Schoellnast H, Deutschmann HA, Quehenberger F, Tillich M. Multiphasic multidetector-row CT (MDCT) in detection and staging of transitional cell carcinomas of the upper urinary tract. Eur Radiol Jun;16(6): Maheshwari E, O'Malley ME, Ghai S, Staunton M, Massey C. Split-bolus MDCT urography: Upper tract opacification and performance for upper tract tumors in patients with hematuria. AJR Am J Roentgenol Feb;194(2): Sudakoff GS, Dunn DP, Guralnick ML, Hellman RS, Eastwood D, See WA. Multidetector computerized tomography urography as the primary imaging modality for detecting urinary tract neoplasms in patients with asymptomatic hematuria. J Urol Mar;179(3):862-7; discussion Wang LJ, Wong YC, Chuang CK, Huang CC, Pang ST. Diagnostic accuracy of transitional cell carcinoma on multidetector computerized tomography urography in patients with gross hematuria. J Urol Feb;181(2):524-31; discussion Chlapoutakis K, Theocharopoulos N, Yarmenitis S, Damilakis J. Performance of computed tomographic urography in diagnosis of upper urinary tract urothelial carcinoma, in patients presenting with hematuria: Systematic review and meta-analysis. Eur J Radiol Feb;73(2): Roupret M, Zigeuner R, Palou J, Boehle A, Kaasinen E, Sylvester R, et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol Apr;59(4): Page 51 of 51