1. TUMORS OF THE KIDNEY

2. BACKGROUND Renal cell carcinoma (RCC) accounts for about 2% of all cancers, with a world-wide annual increase of 1.5 - 5.9%. The mean age at the time of diagnosis is about 60-70 years and there is a predominance of men over women in the range of 1.5 - 3.1. The mortality from RCC is increasing parallel to trends in incidence. World-wide mortality is expected to increase from 54,000 deaths in 1985 to 102,000 deaths in 2000.

3. BACKGROUND Described in 1833 by Grawitz, the tumor has since been known by such names as Grawitz`s tumor, hypernephroma, and clear cell carcinoma. Described in 1833 by Grawitz, the tumor has since been known by such names as Grawitz`s tumor, hypernephroma, and clear cell carcinoma.

4. Classification of Renal Tumours In 1978 RCC was for the first time staged according to TNM staging system proposed by International Union Against Cancer (UICC). In 1978 RCC was for the first time staged according to TNM staging system proposed by International Union Against Cancer (UICC). The TNM classification was revised in 1987 and recently in 1997. The TNM classification was revised in 1987 and recently in 1997.

5. TNM (UICC, 2002) classification of RCC Tx – primary tumour cannot be assessed; Tx – primary tumour cannot be assessed; T o - no evidence of primary tumour; T o - no evidence of primary tumour; T 1 - tumour < 7 cm in greatest dimension limited to the kidney; T 1 - tumour < 7 cm in greatest dimension limited to the kidney; T 1a - tumour 4 cm or less; T 1a - tumour 4 cm or less; T 1b- tumour more than 4 cm but not more than 7 cm T 1b- tumour more than 4 cm but not more than 7 cm T 2 - tumour > 7 cm in greatest dimension limited to the kidney; T 2 - tumour > 7 cm in greatest dimension limited to the kidney; T 3 - tumour extends into major veins or involve adrenal or perinephric tissues but not beyond Gerota's fascia; T 3 - tumour extends into major veins or involve adrenal or perinephric tissues but not beyond Gerota's fascia; T 3a - tumour invades adrenal gland or perinephric tissues but not beyond Gerota's fascia; T 3a - tumour invades adrenal gland or perinephric tissues but not beyond Gerota's fascia; T 3b - tumour grossly extends into renal vein or vena cava; T 3b - tumour grossly extends into renal vein or vena cava; T 3c - tumour grossly extends into vena cava above the diaphragm; T 3c - tumour grossly extends into vena cava above the diaphragm; T 4 - tumour invades beyond Gerota's fascia T 4 - tumour invades beyond Gerota's fascia N O - no regional lymph node metastasis; N O - no regional lymph node metastasis; N 1 - metastasis to a single regional lymph node; N 1 - metastasis to a single regional lymph node; N 2 - metastasis in more than one regional lymph node; N 2 - metastasis in more than one regional lymph node; M O - no distant metastases; M O - no distant metastases; M 1 - distant metastasis. M 1 - distant metastasis.

6. Cytology Normal urothelium Low grade tumor G1 High grade tumor G3

7. Clinical Clinical Findings Clinical symptoms of RCC, such as haematuria, palpable tumour and flank pain, are becoming less frequent. Clinical symptoms of RCC, such as haematuria, palpable tumour and flank pain, are becoming less frequent. Asymptomatic tumours are more commonly diagnosed. Asymptomatic tumours are more commonly diagnosed.

8. Clinical Findings Total haematuria (60-88 %) is shown. It appears suddenly or on the pain background in area of kidney. Total haematuria (60-88 %) is shown. It appears suddenly or on the pain background in area of kidney. Sometimes after haematuria there is the typical attack of kidney colic that is halted together with out development of blood clots (4-10 sm). Sometimes after haematuria there is the typical attack of kidney colic that is halted together with out development of blood clots (4-10 sm).

9. Clinical Findings Distant metastases, at the time of diagnosis, are found in 30% of patients. Distant metastases, at the time of diagnosis, are found in 30% of patients. Symptoms owing to metastatic disease probably occurs more frequently. Symptoms owing to metastatic disease probably occurs more frequently.

10. Clinical Findings The varicocele determined in the neglected stages of disease. The varicocele determined in the neglected stages of disease. The causes of its appearance are: The causes of its appearance are: a) clench or germination by tumor of left kidney venues; a) clench or germination by tumor of left kidney venues; b) clench by tumor or metastases in the lymphatic vessels of lower hollow venes; b) clench by tumor or metastases in the lymphatic vessels of lower hollow venes; c) tumular thrombosis of lower hollow venes or kidney venes. c) tumular thrombosis of lower hollow venes or kidney venes.

11. Ultrasonography This procedure should be initial in diagnosis of the urinary tract. This procedure should be initial in diagnosis of the urinary tract. Ultrasonography allows to distinguish solid mass from the cyst. Probability of detection of 3 cm tumour is 95%. Ultrasonography allows to distinguish solid mass from the cyst. Probability of detection of 3 cm tumour is 95%. The diagnostic capabilities of sonographic Doppler analysis of blood flow allow noninvasive recognition of the vascular pathology. The multiplanar capability of US demonstrates the extent of the tumour. The diagnostic capabilities of sonographic Doppler analysis of blood flow allow noninvasive recognition of the vascular pathology. The multiplanar capability of US demonstrates the extent of the tumour. US is also unable to detect muscle inavasion. US is also unable to detect muscle inavasion.

12. Ultrasonography

13. Computed tomography Standard radiological procedure is an abdominal CT-scan with and without contrast medium. Standard radiological procedure is an abdominal CT-scan with and without contrast medium. It serves to document the diagnosis of RCC and provides information on the function and morphology of the contralateral kidney. It serves to document the diagnosis of RCC and provides information on the function and morphology of the contralateral kidney. The tumours can demonstrate local invasion into the fat within Gerota’s fascia and to the adjacent organs. The tumours can demonstrate local invasion into the fat within Gerota’s fascia and to the adjacent organs. The reported accuracy rate for CT in staging renal tumours ranges between 72 % and 98 %. The reported accuracy rate for CT in staging renal tumours ranges between 72 % and 98 %.

14. X-Ray Findings Plain film allows in many cases to suspect the presence of the tumour by: Plain film allows in many cases to suspect the presence of the tumour by: enlargement of whole or part of the kidney; enlargement of whole or part of the kidney; changing of the shape of kidney, abnormal position of the organ; changing of the shape of kidney, abnormal position of the organ; presence of calcifications. presence of calcifications.

15. X-Ray Findings Excretory Urography – IVP Excretory Urography – IVP Simple cysts or tumours may be diagnosed by this method with 90% accuracy. Simple cysts or tumours may be diagnosed by this method with 90% accuracy. Polar enlargement of a kidney is one of the most frequent pyelographic changes. Polar enlargement of a kidney is one of the most frequent pyelographic changes. The renal outline may be altered and markedly irregular. The renal outline may be altered and markedly irregular.

16. X-Ray Findings Renal arteriography; aortography; phlebography an inferior vena cavography Renal arteriography; aortography; phlebography an inferior vena cavography

17. Magnetic Resonance Imaging MRI provides a detailed display of renal anatomy. MRI provides a detailed display of renal anatomy. MRI is highly sensitive in demonstrating hemorrhage, hemorrhagic cyst. MRI is highly sensitive in demonstrating hemorrhage, hemorrhagic cyst. MRI is the best noninvasive method for the assessment of tumour thrombi in the renal veins or in the inferior vena cava. MRI is the best noninvasive method for the assessment of tumour thrombi in the renal veins or in the inferior vena cava.

18. Instrumental Examination Cystoscopy should be done immediately when gross bleeding is present. Cystoscopy should be done immediately when gross bleeding is present. Blood may be seen spurting from one ureteral orifice, which localizes the source of bleeding. Blood may be seen spurting from one ureteral orifice, which localizes the source of bleeding. During cystoscopy, the physician should search for other urothelial tumors on the bladder or urethral walls. During cystoscopy, the physician should search for other urothelial tumors on the bladder or urethral walls.

19. Treatment Surgical treatment Surgical treatment Non- surgical treatment: Non- surgical treatment: embolisation of the kidney; embolisation of the kidney; radiotherapy; radiotherapy; hormonal therapy; hormonal therapy; chemotherapy; chemotherapy; immunotherapy immunotherapy

20. Surgical Treatment The fundamental principles of radical surgery are following: - choice of the best incision - preliminary ligation of the renal artery - lymphadenectomy - complete excision of the tumour - control and removal the tumour extending into the inferior vena cava - excision of resectable distant metastases

21. Radical Nephrectomy The most important step of the radical nephrectomy is initial ligation of the renal artery and then ligation of the renal vein. This procedure prevents the spread of the tumour cells. The next steps are: the mobilization of the kidney, the division of the ureter and exenteration of the renal lodge by,,en bloc" removal of the kidney, adrenal and perirenal fat with Gerota's fascia. During radical nephrectomy hilar, pericaval or periaortal lymphadenectomy is also performed.

22. Radical Nephrectomy

23. Conservative Surgery of Renal Tumours Conservative surgery for RCC may be identified with two types of procedures: enucleation of the tumours (tumourectomy) and partial nephrectomy. Usually, clamping of the renal artery is unnecessary but if it was indicated regional hypothermia should be considered.

24. Lapascopy nephrectomy

25. Urothelial cancer 8% of malign. Kidney tumors Age - 60-70 y.o. male:female 2:1

26. Symptoms painless hematuria Pain in the back Disuria Colic pain (rare) non-specific late symptoms -appetite loss   weight loss   fatigue

27. Diagnostics US IVP Retrograde ureteropyelography Cytology Uretero-renoscopy CT/ MRI

28. IVP Retrograde

29. Treatment Nephrureterectomy Nephrureterectomy Laser coagulation Laser coagulation Operative Chemotherapy Chemotherapy Adjuvant

30. Treatment removing Kidney Ureter Part of the bladder

32. BLADDER CANCER

33. BACKGROUND The incidence of bladder carcinoma is rising in Western countries. The incidence of bladder carcinoma is rising in Western countries. In 1996, approximately 53,000 patients were diagnosed with bladder cancer in the USA, 9,000 in France, 2,000 in Sweden 8,000 in Spain and 1,120 in Belgium. In 1996, approximately 53,000 patients were diagnosed with bladder cancer in the USA, 9,000 in France, 2,000 in Sweden 8,000 in Spain and 1,120 in Belgium.

34. Pathology of urinary bladder tumours Over 90% of all bladder tumour arise from the transitional epithelium. Over 90% of all bladder tumour arise from the transitional epithelium. The criteria for diagnosis of malignancy in urinary bladder are based on cellular anaplasia, invasion or metastasis. The criteria for diagnosis of malignancy in urinary bladder are based on cellular anaplasia, invasion or metastasis.

35. Histological grading of World Health Organisation and International Pathology Concensus Committee 1988 PTNM pathological classification PTNM pathological classification The pT, pN, and pM categories correspond to the T, N, and M categories. The pT, pN, and pM categories correspond to the T, N, and M categories. G - Histopathological grading G - Histopathological grading G X - Grade of differentiation cannot be assessed G X - Grade of differentiation cannot be assessed G 1 - Well differentiated G 1 - Well differentiated G 2 - Moderately differentiated G 2 - Moderately differentiated G3-4 - Poorly differentiated/undifferentiated G3-4 - Poorly differentiated/undifferentiated

36. 2002 TNM classification of urinary bladder cancer T - Primary tumour T - Primary tumour TX -Primary tumour cannot be assessed TX -Primary tumour cannot be assessed T0- No evidence of primary tumour T0- No evidence of primary tumour Ta- Non-invasive papillary carcinoma Ta- Non-invasive papillary carcinoma Tis - Carcinoma in situ: 'flat tumour‘ Tis - Carcinoma in situ: 'flat tumour‘ T1-Tumour invades subepithelial connective tissue T1-Tumour invades subepithelial connective tissue T2-Tumour invades muscle T2-Tumour invades muscle T2a-Tumour invades superficial muscle (inner half) T2a-Tumour invades superficial muscle (inner half) T2b-Tumour invades deep muscle (outer half) T2b-Tumour invades deep muscle (outer half) T3-Tumour invades perivesical tissue: T3-Tumour invades perivesical tissue: T3aMicroscopically T3b-Macroscopically (extravesical mass) T3aMicroscopically T3b-Macroscopically (extravesical mass) T4-Tumour invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall T4-Tumour invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall T4a-Tumour invades prostate, uterus or vagina T4a-Tumour invades prostate, uterus or vagina T4b-Tumour invades pelvic wall or abdominal wall T4b-Tumour invades pelvic wall or abdominal wall

37. 2002 TNM classification of urinary bladder cancer N - Lymph nodes N - Lymph nodes NX -Regional lymph nodes cannot be assessed NX -Regional lymph nodes cannot be assessed N0 - No regional lymph node metastasis N0 - No regional lymph node metastasis N1 - Metastasis in a single lymph node 2cm or less in greatest dimension N1 - Metastasis in a single lymph node 2cm or less in greatest dimension N2 - Metastasis in a single lymph node more than 2 cm but not more than 5 cm in greatest dimension, or multiple lymph nodes, none more than 5 cm in greatest dimension N2 - Metastasis in a single lymph node more than 2 cm but not more than 5 cm in greatest dimension, or multiple lymph nodes, none more than 5 cm in greatest dimension N3 - Metastasis in a lymph node more than 5 cm in greatest dimension N3 - Metastasis in a lymph node more than 5 cm in greatest dimension M - Distant metastasis M - Distant metastasis MX - Distant metastasis cannot be assessed MX - Distant metastasis cannot be assessed M0 - No distant metastasis M0 - No distant metastasis M1 - Distant metastasis M1 - Distant metastasis

38. BLADDER CANCER Approximately 75-85% of patients present with disease confined to the mucosa (stage Ta-Tis) or submucosa (stage T1). Approximately 75-85% of patients present with disease confined to the mucosa (stage Ta-Tis) or submucosa (stage T1). The other 15-25% have muscle invasion or nodal disease (stages T2-T4, N+) at presentation. The other 15-25% have muscle invasion or nodal disease (stages T2-T4, N+) at presentation.

39. Symtomatology Haematuria is the most common finding in bladder cancer. The degree of haematuria does not correlate with the extent of the disease. It may be grossly visible to the patient or simply found on routine urinalysis. Bladder cancer may also present symptoms of voiding irritability. Patients may complain of urgency, dysuria and increased urinary frequency.. Urinary tract infection is observed in 30% of patients.

40. Symtomatology Pain appears in advanced stages of the tumour. Pain appears in advanced stages of the tumour. When it is located in the suprapubic region it signals that the tumour infiltrates the perivesical tissues. When it is located in the suprapubic region it signals that the tumour infiltrates the perivesical tissues. Flanc pain, often accompanied by fever, is due to the ureteral obstructions. Flanc pain, often accompanied by fever, is due to the ureteral obstructions.

41. DIAGNOSIS Physical examination Physical examination, including digital rectal examination and bimanual pelvic palpation, is recommended when haematuria is found. However, 85% of patients with bladder cancer initially present with superficial disease. Therefore, physical examination plays a limited role in the diagnosis, except to exclude co-existing pathology.

42. Laboratory Findings Urinalysis Urinalysis is performed either using a dipstick test or by examination of urinary sediment following centrifugation. It is used to determine if the patient has - Haematuria - Proteinuria - Pyuria Renal-function assessment - Should be determined by serum creatinine test

43. X-Ray Findings Urography with cystography are performed in all patients suspected of bludder tumours. Urography with cystography are performed in all patients suspected of bludder tumours. Filling defects in the central part of the cystogram can indicate the papillary growth of the tumour. Filling defects in the central part of the cystogram can indicate the papillary growth of the tumour. Marginal filling defects are typical of flat tumours, which are always invasive. Marginal filling defects are typical of flat tumours, which are always invasive.

44. X-Ray Findings Intravenous pyelography IVP Intravenous pyelography (IVP) is also used to detect filling defects in the calices, renal pelvis and ureters, and hydronephrosis, which may indicate the presence of a ureteral cancer or a muscle-invasive bladder cancer at the ureteral orifice.

45. X-Ray Findings Ureterohydronephrosis signals the muscle- invasive growth of the tumour in 70-90% of cases. Ureterohydronephrosis signals the muscle- invasive growth of the tumour in 70-90% of cases.

46. X-Ray Findings

47. DIAGNOSIS Imaging (metastasis) In order to specify staging of the bladder tumour, besides clinical examination, USG and bimanual investigation of patients, following additional procedures are performed: In order to specify staging of the bladder tumour, besides clinical examination, USG and bimanual investigation of patients, following additional procedures are performed: - transurethral diagnostic (primary) resection - transurethral diagnostic (primary) resection - transurethral ultrasonography - transurethral ultrasonography - computed tomography of pelvis minor, retroperitoneum and liver - computed tomography of pelvis minor, retroperitoneum and liver - magnetic resonance of pelvis minor and bones - sites suspected of the metastases, - magnetic resonance of pelvis minor and bones - sites suspected of the metastases, - chest radiograph. - chest radiograph.

48. Ultrasonography Ultrasonography This procedure should be initial in diagnosis of the urinary tract. Ultrasonography This procedure should be initial in diagnosis of the urinary tract.

49. CT Computed tomography is of little use in the diagnosis of bladder cancers. Computed tomography is of little use in the diagnosis of bladder cancers.

50. Cystoscopic Examination The diagnosis of bladder cancer ultimately depends on cystoscopic examination of the bladder and pathological evaluation of the resected lesion. The diagnosis of bladder cancer ultimately depends on cystoscopic examination of the bladder and pathological evaluation of the resected lesion. Cystoscopy shows the size of the tumour, its appearance and surrounding. Cystoscopy shows the size of the tumour, its appearance and surrounding.

51. DIAGNOSIS Biopsy Biopsy is also applied the histology of the tumour as well as its grade can be determined. Biopsy is also applied the histology of the tumour as well as its grade can be determined. The biopsy of non-affected parts of the bladder should be obtained in search of carcinoma in situ. The biopsy of non-affected parts of the bladder should be obtained in search of carcinoma in situ.

52. Differential Diagnostics

54. Treatment The discrimination between noninvasive tumours (Ta, Tl) and invasive ones (T2-T4) is very important because of the difference in the treatment of them. The discrimination between noninvasive tumours (Ta, Tl) and invasive ones (T2-T4) is very important because of the difference in the treatment of them. Additionally, on the method of treatment influences grading of neoplasmatic cells atypia (symbol G). Additionally, on the method of treatment influences grading of neoplasmatic cells atypia (symbol G).

55. Surgical treatment Three methods of surgical treatment are commonly used in bladder cancer. Three methods of surgical treatment are commonly used in bladder cancer. These are: transurethral resection, partial cystectomy and radical cystoprostatectomy. These are: transurethral resection, partial cystectomy and radical cystoprostatectomy. The choice of the appropriate procedure is determined by the following factors: tumour stage, grade and multifocal growth. The choice of the appropriate procedure is determined by the following factors: tumour stage, grade and multifocal growth.

56. Transurethral resection Transurethral resection as primary therapy should be reserved for patients who have small, solitary, low grade superficial carcinomas and bladder papillomas. Transurethral resection as primary therapy should be reserved for patients who have small, solitary, low grade superficial carcinomas and bladder papillomas. The procedure makes it possible to remove deep layers of the bladder muscle, which renders the treatment more radical. The procedure makes it possible to remove deep layers of the bladder muscle, which renders the treatment more radical.

57. Partial resection of the bladder Partial resection of the bladder is performed rarely. Partial resection of the bladder is performed rarely. The treatment is reserved for patients with solitary muscle-infililtrative tumours localised on top of the bladder, far from the trigone or vesicle neck. A tumour- free margin of 1,5 to 2,0 cm must be obtained. The treatment is reserved for patients with solitary muscle-infililtrative tumours localised on top of the bladder, far from the trigone or vesicle neck. A tumour- free margin of 1,5 to 2,0 cm must be obtained.

58. Partial resection of the bladder

59. Radical cystectomy Indications for the operation. Indications for the operation. These are : 1 - 1 - invasive bladder cancer irrespective of the tumour grade, 2 - recurrences of the tumour after transurethral resection, particularly when the grade increases, 3 - high grade tumours coexisting with carcinoma in situ, 4 - multifocally growing superficial bladder cancers resistant to intravesical chemo- or immunotherapy administered after transurethral resection,. 5 - recurrences of carcinoma in situ following chemo- or immunotherapy.

60. Radical cystectomy

61. Urinary diversion after radical cystectomy

63. Radiotherapy Poorly differentiated or multiple T1-T2 tumours may be treated by local radiotherapy to the bladder and perivesical tissues with five- year survival rates of 40-60%. Poorly differentiated or multiple T1-T2 tumours may be treated by local radiotherapy to the bladder and perivesical tissues with five- year survival rates of 40-60%.

64. Intravesical chemotherapy Table : Advantages and disadvantages of therapeutic compounds used in treatment of bladder cancer Name Molecular weigh t AdvantagesDisadvantages Therapeutic use ThiotepaSmallInexpensive Systemic absorption leading to myelosuppression and renal failure +/- EpodylSmallInexpensive Systemic side-effects; myelosuppression +/- AdriamycynLargeMinimal absorptionChemical cystitis; expensive+ EpirubicinLargeMinimal absorptionChemical cystitis; expensive+ Mitomycin CLargeMinimal absorption Chemical cystitis, bladder ulceration; expensive + Mitoxantron CLargeMinimal absorptionChemical cystitis, expensive+ BCGLarge Relatively inexpensive Local toxicity, BCG-itis (absorption)+ + + Cytokines InterferonRelatively small EffectiveSystemic toxicity; extremely expensive +

65. THANK YOU FOR ATTENTION