Approach to Upper Urinary Tract Tumors.pptx

Approach to Upper Urinary Tract Tumors

1. Approach to Upper Urinary Tract Tumors Dr. Akshay Sarraf 2nd Year Resident Dept. of General surgery

2. I ntroduction U pper urinary tract consist of the kidneys and ureters. The kidneys are paired retroperitoneal organs. Kidneys are end organs, which are responsible for their vulnerability to infarction. Ureters are smooth muscle–based tubular structures that connect the renal pelvis to the bladder.

3. Renal masses can be malignant, benign, or inflammatory. Can also be classified based on radiographic appearance (simple cystic, complex cystic, solid). Clinical evaluation is extremely important in the assessment of the risk of malignancy and metastatic potential Include patient characteristics and mode of presentation, imaging characteristics, laboratory evaluation, and renal mass biopsy (RMB).

4. The strongest predictors of malignancy are male sex and increasing tumor size ( Pierorazio et al., 2016 ). Men have a nearly threefold increased risk of malignancy. 20% to 30% of renal masses less than 4 cm and 40% of renal masses less than 2 cm are benign. Majority of renal masses are discovered via incidental imaging.

5. Ultrasonography can differentiate cystic versus solid renal masses. USG criteria for simple cyst include- a smooth cyst wall, a round or oval shape without internal echoes, and through-transmission with strong acoustic shadowing posteriorly CEUS using microbubbles used for the characterization and assessment of enhancement of renal masses; may play an important role in patients with CKD in the future.

6. Radiographic evaluation of a renal mass remains the strongest predictor of malignancy and metastatic potential ( Pierorazio et al., 2016 ). Intravenous pyelography and renal arteriography are no longer recommended in the routine evaluation of renal masses. Current guidelines recommend multiphase, cross-sectional imaging. A dedicated renal CT with and without the administration of contrast remains the most important radiographic test for delineating the nature of a renal mass.

7. Enhancement of greater than 15 to 20 Hounsfield units (HU) is indicative of RCC. Solid masses with CT attenuation numbers (below − 20 HU) indicative of fat are diagnostic for angiomyolipoma (AML) MRI is the alternate standard imaging modality for the characterization of a renal mass Enhancement of greater than 20% with intravenous G d-based MRI is suggestive of RCC particularly in masses smaller than 2 cm.

8. Imaging should comment on- Renal mass diameter in craniocaudal, transverse, and AP dimensions; Tumor morphology, including involvement of or juxtaposition to the renal hilum, vein, or collecting system; Enhancement characteristics; and Associated features such as retroperitoneal lymphadenopathy and presence or absence of abdominal metastases.

9. Tumor location and complexity describe the relationship of the mass with the renal hilum, collecting system, polarity, and endophytic versus exophytic location. Complexity profiles include- R.E.N.A.L. (Radius, Endophytic vs. exophytic, Nearness to collecting system, Anterior/posterior, Location relative to polar lines) Nephrometry score, the PADUA score, and the C-index

10. Urothelial cancer, lymphoma, infectious processes, and high-grade or sarcomatoid RCC commonly demonstrate infiltrative growth patterns and indistinct borders on imaging. FDG-PET-CT has a limited role in RCC because of its high levels of visual conspicuity in the kidney and at the most common sites of metastatic disease 99mTc-sestamibi SPECT is useful in distinguishing renal oncocytoma and hybrid oncocytic /chromophobe tumors from clear cell RCC; awaits large-scale validation

11. Evaluation of Cystic Renal Lesions- Differentiation between benign renal cysts and cystic RCC remains a common and challenging problem. Simple cysts are thin-walled, fluid-filled structures with a nearly zero risk of malignancy Cyst complexity is defined by evaluation of the wall of the lesion; its thickness and contour; the number, contour, and thickness of any septa; the amount, character, and location of any calcifications; the density of fluid in the lesion; the margination of the lesion; and the presence of solid components.

12. Benign Renal Tumours Incidental detection owing to the widespread use of abdominal imaging. The lesions may be cystic or solid. Solid renal tumours should be considered malignant unless proven otherwise. 

13. Renal Oncocytoma- HPE- uniformly highly granular eosinophilic cytoplasm owing to abundant mitochondria (oncocyte) is seen.  Accounts for around 5% of renal tumours .  Appears as an enhancing mass on cross-sectional imaging and is difficult to differentiate from RCC.  Presents at around the seventh decade and have a male preponderance. It coexists with RCC in approximately 10% of cases. 

14. Differentiated by the use of immunohistochemistry staining, where chromophobe RCC stains positive for cytokeratin-7.  On axial imaging- presence of central stellate scarring and a spoke wheel appearance in the angiographic phase.  Nephron-sparing surgery, such as partial nephrectomy, should be the preferred option  Diagnosis is usually confirmed after removal 

15. Renal Angiomyolipoma- Comprises a composite mix of fat tissue with dysmorphic blood vessels and smooth muscle.  Most often detected incidentally and has a female preponderance.  May be sporadic or associated with syndromes such as the tuberous sclerosis complex a/ w activation of the mTOR pathway.  Mostly asymptomatic; however, most common cause of spontaneous retroperitoneal hemorrhage. Pregnancy is a potential risk factor for bleeding. 

16. US shows a bright echogenic mass lesion on account of the high fat content. CT scan shows an intralesional fat density of –15 to –20 Hounsfield units (HU) within the mass, which is the hallmark of an angiomyolipoma radiological diagnosis. Treatment depends on size, presence of symptoms, and pregnancy status Tumours <4 cm can be followed up.

17. Nephron-sparing surgery such as partial nephrectomy is the preferred option. Angioembolisation is the preferred modality of choice in the setting of acute haemorrhage .  mTOR pathway inhibitor, such as everolimus and sirolimus, have excellent response rates in subgroup of patients with the tuberous sclerosis complex. 

18. Metanephric Adenoma Rare benign epithelial lesion in the kidney Represents approximately 0.2% of renal masses Peaks in the fifth decade; 2 : 1 female:male ratio 50% diagnosed incidentally; the remainder present with flank pain, gross hematuria, a palpable mass, and polycythemia.

19. Metanephric adenoma may exist on a continuum with Wilms tumors and papillary RCC Stain positive for Wilms tumor protein WT1 and CD57 and negative for α- methylacyl CoA racemase (AMACR), papillary RCC stains oppositely Radiographic findings insufficient for diagnosis, and as such, often diagnosed after surgical resection. If high suspicion, fine-needle aspiration to perform IHC staining. Management is often nephron sparing such as partial nephrectomy or thermal ablation.

20. Upper tract urothelial cancer  Primary urothelial neoplasms of the renal pelvis and ureter are rare.  Accounts for less than 10% of all urothelial tumours .  more common in adult men.  Important risk factors are Tobacco consumption, Occupations in the dye, petrochemicals and rubber industries, Analgesic abuse, High arsenic content in drinking water, Exposure to cyclophosphamide and Presence of chronic inflammation (also a/w squamous cell carcinoma).

21. Commonly present with gross haematuria , with or without flank pain and occasionally clot colic.  Passage of long, slender, worm-like clots is suggestive of upper tract involvement.  Few present with advanced constitutional symptoms and a palpable mass.  Microscopic haematuria should be evaluated in high-risk adult (chronic smokers, occupational exposure, older age) population. 

22. Urinalysis may reveal numerous RBCs and white blood cells. Urine cytology- presence of atypical or malignant cells in a freshly voided sample has a high specificity.  CTU is the investigation of choice- radiolucent filling defects, incomplete visualisation of calyces and the presence of hydronephrosis.  Flexible ureterorenoscopy - to visualise the ureter, renal pelvis and collecting system and to biopsy suspicious lesions.

23. Unifocal, small (<1 cm), low-grade disease with no evidence of invasion on CTU is characterised as a low-risk tumour . Upper tract urothelial cancers that invade the muscle wall usually have poor prognosis. The 5-year survival is <50% and <10% for pathologically proven T2/T3 and T4 tumours , respectively. 

24. Low-risk localised tumours may be managed with endoscopic ablation or segmental excision. Kidney-sparing surgery is important in patients with solitary kidney, renal insufficiency and synchronous bilateral tumours .  High-risk tumours warrant radical nephroureterectomy with bladder cuff resection with or without lymphadenectomy.   Locally advanced disease is usually treated with cisplatinum -based neoadjuvant chemotherapy to downstage the disease prior to surgical ablation. 

25. Renal Cell Carcinoma Most common solid neoplasm of the kidney. Accounts for around 90% of renal tumours and constitutes 2–5% of all cancers in adult men and 1–3% in adult women. May be sporadic or familial.  Most commonly associated familial syndrome- von Hippel–Lindau (VHL).  VHL- rare autosomal dominant disorder characterised by clear-cell RCC( ccRCC ), phaeochromocytoma,retinal -angiomas, haemangioblastomas of the brainstem, cerebellum or spinal cord. 

26. Risk factors- Cigarette smoking, obesity and hypertension. Diuretics, occupational exposure to petrochemicals and dyes and ARCD in patients on long-term haemodialysis .  C linical Presentation- Classic triad of flank pain, haematuria (m/c) and a palpable mass. Constitutional symptoms such as fever, malaise and weight loss in advanced disease.  Bilateral lower limb oedema or recent-onset non-reducing right-sided varicocele 

27. Paraneplastic Syndromes Found in up to one-third of patients with RCC.  Elevated erythrocyte sedimentation rate (ESR), hypertension, anaemia and hypercalcaemia .  Quarter of the patients may have evidence of metastatic disease on presentation(m/c cannon ball mets , pathological fractures).

28. Pathology Are adenocarcinoma arising from the proximal renal tubular epithelium.  Are slow growing and bulge out of the renal contour Most are solitary, but bilateral and multiple tumours are found in familial RCC.  Can spread directly, invading the perinephric tissue through the capsule or at times directly extending into the renal vein as a tumour thrombus.

29. Diagnosis Laboratory Tests- Blood count, ESR, serum creatinine, LFT, LDH, corrected serum calcium, coagulation markers and urine analysis.  Increased ALP should prompt further investigation to rule out liver and skeletal metastases.  Radiological- Triphasic CECT is the investigation of choice for diagnosis and staging.  Typically shows contrast enhancement after contrast injection (a change of >15 HU is considered significant)  Also provides additional information on the function of the opposite kidney, primary tumour extension, venous involvement, enlargement of regional lymph nodes, the status of the adrenal glands and intra-abdominal metastatic disease 

30. MRI- superior at detecting tumour infltration into the vein wall and the level of thrombus.  A chest radiograph should be obtained in all cases. A bone scan is necessary in a patient with elevated alkaline phosphatase, bone pain or hypercalcaemia .  Prognostic Factors-

31. T reatment- Parti al nephrectomy for small renal masses ( tumours <4 cm). Use of laparoscopy or robots have reduced postoperative morbidity.  Surveillance, cryoablation or radiofrequency ablation of small renal tumours may be offered in patients with high surgical risks. Radical nephrectomy gold standard for localised disease Involves removal of the entire kidney enclosed in Gerota’s fascia with  Lymphadenectomy is indicated only in high-risk patients with large primary tumours and enlarged lymph nodes. 

32. Tyrosine kinase inhibitors (sunitinib, pazopanib) have improved survival in metastatic ccRCC .  RCC responds to immunotherapy. 1 st Gen- interleukins and interferons. Targeted therapy- immune checkpoint inhibitors and anti-programmed death 1/programmed death ligand-1 inhibitors have been used.  Cytoreductive nephrectomy- in good and intermediate-risk patients. Palliative nephrectomy may be considered for intractable haematuria , pain and symptomatic PNS Angioembolisation of renal tumour can be performed in medically unfit patients with intractable haematuria . 

33. Wilm’s Tumour- Most common tumour of childhood, 5% of all childhood cancers.  Bilateral in 5% of cases and familial in 1%.  Has mixed elements derived from the embryonic blastemal or undifferentiated tissue, epithelial tubules and stroma.  Seen in c hild aged between 1 and 4 years of either gender with a large, palpable abdominal mass that may cross the midline.  Associated with haematuria , hypertension, fever and weight loss. 

34. Large tumour can rupture and present as an acute abdomen.  US can confirm the renal origin and solid nature of the mass. Definitive imaging with either CECT or MRI is necessary to stage the disease.  Usually infiltrate the kidneys and normal renal parenchyma is compressed at the periphery around the tumour ( claw sign ).  Current treatment is nephrectomy with pre- or postoperative chemotherapy; Both regimes have a comparable survival of ~90%. 

35. References 1. Bailey & Love’s Short Practice of Surgery, 28 th Edition. 2. Campbell-Walsh-Wein Urology, 12 th Edition. 42

36. THANK YOU 43