1. Skeletal Metastases in Malignant Tumors Prof. Dr. Nazem Shams Professor of General Surgery & Surgical Oncology Faculty of Medicine Mansoura University

2. Post-graduate Course Introduction Importance of dealing with this subject originating from recent methods of management – even in late terminal cases- for better quality of life rather than aiming for cure.

3. Post-graduate Course Metastatic Potential of Tumors The development of metastasis is a complex and highly selective process that is dependant upon the interplay of host and intrinsic characteristics of tumor cells, adhesive capacities, cell motility, enzyme secretion and others.

4. Post-graduate Course Routes of Metastasis The routes by which cancer cell emboli ordinarily reach the skeleton is the blood stream (venous or arterial). The role taken by lymphatic is not important due to apparent absence of lymph channels in bone marrow, There is also a minute role for perineural spread.

5. Post-graduate Course Routes of Metastasis 1. Venous Route.  Vertebral venous system which is a network of valveless veins around the spinal dura mater and the vertebrae.  This system has cranial and body wall connection and even connections with the veins in the wall of the vessels of extermities.  When the intrathoracic or intra-abdominal pressure rises, as in coughing or sneezing, a reversed flow in the venous vertebral system can occur.

6. Post-graduate Course Routes of Metastasis 2. Arterial Spread:  Cancer cell emboli reaching the lungs by way of caval circulation sometimes pass through the lungs instead of being arrested in them.

7. Post-graduate Course Routes of Metastasis 3. Perineural Spread:  Perineural space via the fifth cranial nerve have been speculated.

8. Post-graduate Course Theories of Metastasis 1. Anatomical 2. Soil & seed 3. Surface properties.

9. Post-graduate Course Incidence of Bone Metastasis The overall incidence of skeletal metastasis rates 70% or more. If one considers the prostate, kidney and thyroid, the incidence of skeletal metastasis in cases which have run their full clinical course. Sometimes the primary lesion is clinically silent and bone metastasis gives the first information about the presence of tumor as in kidney, lung and pancreas as well as lymphoma.

10. Post-graduate Course Sites of Bone Metastasis The vertebral column particularly in the lumbar area and the sacrum, the rib cage including the sternum, the femoral and humeral shafts, the pelvic bones and the calvarium are the general sites of predilection.

11. Post-graduate Course Common Sources of Metastasis to Bone Percent of Metastatic bony involvementPrimary site 50-85%Breast 50-75%Prostate 30-50%Renal 30-50%Lung 39%Thyroid 8%Liver 5-10%Pancreas 5-10%Colorectal 5-10%Gastric 2-6%Ovary

12. Post-graduate Course Sites of Bone Predilection for Metastasis in Each Tumor The commonly affected bonePrimary Tumor Vertebrae especially the thoracic vertebrae Proximal femur 1. Breast Thoracic & Lumbar vertebrae and pelvis 2. Prostate Thoracic vertebrae 3. Lung Thoracic vertebrae 4. Kidney Lumbaosacral vertebrae 5. G.I.T. Skull, clavicle and tibia 6. Squamous cell carcinoma Femur especially lower femoral diaphysis Humerus especially medial margin of upper humerus Skull 7. Neuroblastoma Upper lumbar & lower thoracic vertebrae Pelvis & ribs 8. Non Hodgkin ’ s lymphoma Facial bones 9. Burkitt ’ s lymphoma Proximal femur Thoracic spine 10. Hodgkin ’ s lymphoma

13. Post-graduate Course Sites of Bone Predilection for Metastasis in Each Tumor The commonly affected bonePrimary Tumor 11. Leukaemia Distal femur & Proximal tibia Humerus Vertebral bodies Iliac crest A. Infant Proximal end of humerus Femur & tibia B. Adult 12. Peripheral lesions in the hand or foot, usually have their origin in the lung, kidney, breast, uterus, oesophagus & melanoma of the skin.

14. Post-graduate Course Clinical Presentation 1. Pain 2. Pathological Fracture 3. Swelling 4. Neurological Manifestations 5. General symptoms 6. Paraneoplastic syndrome

15. Post-graduate Course Diagnostic Approaches I. Laboratory Investigations: 1. Blood picture 2. Blood glucose 3. Blood electrolytes 4. Urine 5. Enzymes 6. Tumor markers

16. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography 2. Myelography 3. Angiography 4. Tomography 5. Bone scanning 6. Computerized axial scan 7. MRI 8. PET

17. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

18. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

19. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

20. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

21. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

22. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

23. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

24. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

25. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

26. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

27. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

28. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 1. Plain radiography

29. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

30. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

31. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

32. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

33. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

34. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

35. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

36. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 2. Myelography

37. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 3. Angiography

38. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 3. Angiography

39. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 3. Angiography

40. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 4. Tomography

41. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 4. Tomography

42. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 4. Tomography

43. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 4. Tomography

44. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 4. Tomography

45. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 4. Tomography

46. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

47. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

48. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

49. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

50. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

51. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

52. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

53. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 5. Bone scanning

54. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 6. Computerized axial scan

55. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 6. Computerized axial scan

56. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 7. MRI

57. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 7. MRI

58. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 7. MRI

59. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 7. MRI

60. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 7. MRI

61. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 8. PET

62. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 8. PET

63. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 8. PET

64. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 8. PET

65. Post-graduate Course Diagnostic Approaches II. Radiological Diagnosis. 8. PET

66. Post-graduate Course Diagnostic Approaches III. Biopsy 1. Needle biopsy 2. Open biopsy

67. Post-graduate Course Types of Skeletal Metastasis Relative Frequency Usual type of skeletal Metastasis Primary focus RareInfrequentCommonVery common xLytic and mixedBreast Lung x Predominantly lytic Carcinoma x Predominantly blastic Carcinoid x Predominantly blastic, lytic in older age group Prostate XLytic-expandingKidney XLytic-expandingThyroid

68. Post-graduate Course Types of Skeletal Metastasis Relative Frequency Usual type of skeletal Metastasis Primary focus RareInfrequentCommonVery common G.I.T xLytic Oesophagus x Predominantly blastic Stomach xx Predominantly lytic, occasionally blastic Colon X Predominantly lytic Rectum Xlytic Biliary Tree XLytic Pancreas

69. Post-graduate Course Types of Skeletal Metastasis Relative Frequency Usual type of skeletal Metastasis Primary focus RareInfrequentCommonVery common Female Reproductive System Xlytic Uterus: Corpus XLytic or mixed Cervix Predominantly lytic Ovary X Predominantly lytic, blastic if prostate is involved Urinary Bladder x Predominantly lytic, occasionally blastic Testis

70. Post-graduate Course Types of Skeletal Metastasis Relative Frequency Usual type of skeletal Metastasis Primary focus RareInfrequentCommonVery common Head, Neck and C.N.S. XLytic or blastic Brain X Lytic, mixed and blastic Neuroblast oma XLytic Paranasal sinuses XLytic or blastic Nasophary nx Skin xLytic Epidermoid xLytic-expanding Melanoma

71. Post-graduate Course Schemes for Treatment of Skeletal Metastasis I. Treatment policy of metastasis II. Treatment of skeletal metastasis 1) Surgical management 2) Radiation therapy 3) Hormonal therapy 4) Chemotherapy 5) Radioneuclide

72. Post-graduate Course Schemes for Treatment of Skeletal Metastasis III. Treatment of complications 1) Pain 2) Pathological fractures 3) Spinal cord compression 4) Hypercalcaemia

73. Post-graduate Course Schemes for Treatment of Skeletal Metastasis IV. Prophylactic treatment 1) Adjuvant chemotherapy 2) Adjuvant hormonal therapy

74. Post-graduate Course Schemes for Treatment of Skeletal Metastasis The treatment policy differs whether the metastasis is solitary or multiple and also differs according to the state of primary cancer and the general condition of the patient.

75. Post-graduate Course Surgical Management of Skeletal Metastasis 1. Amputation: Aims at palliation of pain if extensive cortical destruction around more distal fractures, fungation, intractable pain and vascular insufficiency.

76. Post-graduate Course Surgical Management of Skeletal Metastasis 2. Prophylactic Internal Fixation: Indications:- 1) Impending fracture. 2) Pain 3) Involvement of one-half of the cortex 4) High risk femur  Pure lysis are seen on the roentgneogram  The development of malignant lesion previously not demonstrable in the bone  Involvement of even a small portion of the cortex  Increasing pain  Carcinoma of the lung was the tumor type most likely to be associated with one or more high risk factors  Subtrochantric metastatic bone lesions secondary to carcinoma of the lung

77. Post-graduate Course Radiation Therapy 1. Localized irradiation 2. Hemibody irradiation

78. Post-graduate Course Hormonal Therapy 1) Casteration 2) Oestrogenic hormones 3) Androgenic hormones 4) Progestins 5) Antioestrogens 6) Aminoglutethemide 7) Bilateral adrenalectomy 8) Hypophysectomy 9) Thyroxin

79. Post-graduate Course Cancer Patients Referred for Pain Relief in Pain-clinics 1. Traumatic:  Pathological fractures  Amputation stump and phantom limb pain 2. Skeletal:  Osteolytic lesions  Osteoprosis with consequent degenerative and mechanical changes  Hypercalcaemia

80. Post-graduate Course Cancer Patients Referred for Pain Relief in Pain-clinics 3. Neurological:  Nerve lesions due to compression or invasion  Central pain 4. Diagnostic and psychosomatic problems.

81. Post-graduate Course Destructive Procedures in Treatment of Pain 1) Dorsal rhizotomy 2) Commissural myelotomy 3) Anterolateral cordotomy 4) Trans-sphenoidal haypophysectomy 5) Rhizotomy of the cranial nerves 6) Subarachinoid injection of phenol 7) Intrathecal & extradural opiates

82. Post-graduate Course Management of Spinal Cord Compression Spinal cord compression from malignant tumor metastatic to the epidural space will inevitably result in permanent neurological damage unless emergency measures are taken. It should also be noted that epidural lesions below L 1-2 region can result in compression on the cauda equina rather than the spinal cord itself.

83. Post-graduate Course Bone Metastasis of Unknown Primary Percent of occult primary malignancy presents by bony involvement Percent of Metastatic bony involvement Primary site 4%Lung 33%Breast 28%Pancreas 31%Liver 13%Colorectal 9%Gastric 66%Renal 25%Prostate

84. Post-graduate Course Benign Tumors with Metastasis