The Tumor (T), the Lymph Nodes (N), and the Cancer Spread (M)

Transcription

1 The Tumor (T), the Lymph Nodes (N), and the Cancer Spread (M) Primary tumor (T) TX: Main tumor cannot be measured. T0: Main tumor cannot be found. T1, T2, T3, T4: The size and/or extent of the main tumor. Regional lymph nodes (N) NX: Cancer in nearby lymph nodes cannot be measured. N0: There is no cancer in nearby lymph nodes. N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. Distant metastasis (M) MX: Metastasis cannot be measured. M0: Cancer has not spread to other parts of the body. M1: Cancer has spread to other parts of the body. E. MORAN

2 CORRELATION BETWEEN TUMOR, LYMPH NODES, AND METASTASES 1. In all sites, there is good correlation between the size of the tumor and its local penetration (T), the involvement of lymph nodes (N), and the spread of the cancer to remote sites (metastases) (M) 2. Staging dictates the best treatment 3. Staging weighs heavily on prognosis E. MORAN

3 Cancer Prognosis and Survival Patient s general condition, co-morbidities Performance status Psychological index Tumor histology, grade of aggressiveness Tumor stage (T, N, and M) Treatment modality available Responsiveness to treatment Cancer is no longer the most lethal of chronic diseases. Cancer is now the most chronic of lethal diseases. E. MORAN

4 E. MORAN

5 PSA and the TNM Stage STAGE II III IV NR TOTAL PSA n % n % n % n % n % % 2 1% 2 1% 11 5% 44 21% % 3 1% 5 2% 36 18% 88 43% % 0 0% 2 1% 16 8% 37 18% % 1 0% 1 0% 1 0% 8 4% % 0 0% 1 0% 0 0% 5 2% > % 2 1% 1 0% 1 0% 19 9% % 8 4% 12 6% 65 32% % E. MORAN 2018

6 LECTURE #4 6

7 CANCER TREATMENT 7

8 8

9 E. MORAN

10 E. MORAN

11 E. MORAN

12 CANCER TREATMENT PRINCIPLES Localized Adjuvant ChemoRx + Surgery +/- RT Regional (N+) Surgery + Adjuvant RT + CT +/- ImmunoRx. Metastatic (spread +) ChemoRx, Biologicals, Immunotherapy +/- Surgery for debulking + ChemoRx +/- ImmunoRx +/- Radiation E. MORAN

13 NEW SURGICAL TREATMENTS Debulking the tumor mass Removal of the primary tumor in presence of metastases Removal of metastases in liver, lungs, brain E. MORAN

14 CANCER CHEMOTHERAPY FIRST FINDINGS 14

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16 Principles of Combination Chemotherapy 16

17 ADJUVANT CHEMOTHERAPY E. MORAN

18 IMMUNOTHERAPY OF CANCER Immunotherapy Monoclonal agents Anti-angiogenesis factors Anti-target therapy E. MORAN

19 CELL MEMBRANE RECEPTOR E. MORAN

20 CELL-MEDIATED IMMUNITY T-lymphocytes (activated in the thymus) identify aggressors and try to destroy them through the production of lymphokines (synthesized proteins) Killer T-cells Helper T-cells Suppressor cells E. MORAN

21 HUMORAL IMMUNITY B-lymphocytes (from the bone marrow) synthesize immunoglobulins which function as antibodies combining with foreign antigens (bacteria and viruses): IgG major immunoglobulin (80%) IgM mostly intravascular IgA in body secretions, GI and respiratory tract IgE active in hypersensitivity (allergy) IgD E. MORAN

22 E. MORAN

23 Immunoglobulin Molecule, Antigen, and Antibody Antigen Antigen binding site Antibody 23

24 IMMUNOTHERAPY OF CANCER (1) Active immunotherapy: Non-specific: BCG Levamisole Interferon Interleukin 2 Specific: Tumor antigen vaccines E. MORAN

25 Immunotherapy of Cancer (2) Passive immunotherapy Antibodies: Monoclonal or Polyclonal Antibodies Conjugated with toxins Radiolabeled Cells: Tumor-infiltrating lymphocytes E. MORAN

26 Response to Cancer Immunotherapy % Urinary bladder Kidney cancer Malignant melanoma Cutaneous T-cell lymphoma 80 Lymphoma Multiple myeloma 50 E. MORAN

27 Monoclonal Antibodies to Cancer Cell 27

28 Development of a Malignant Tumor E. MORAN 2018

29 Anti-angiogenesis 29

30 Tumor cells and T cells 30

31 DIAGNOSIS of BLOOD FORMING ORGANS LEUKEMIA 31

32 Active (Normal) Bone Marrow 32

33 Active (Normal) Bone Marrow 33

34 Stem Cell and Blood Cells 34

35 E. MORAN

36 Blood film (smear) to show: Red blood cells, white blood cells (neutrophils), and a platelet E. MORAN

37 LIFETIME OF BLOOD CELLS RBC 120 days WBC days Platelets ~ one week E. MORAN

38 Homeostasis of the White Blood Cells 38

39 Leukemia Microscopic view of the bone marrow E. MORAN

40 Clinically: ACUTE VS. CHRONIC LEUKEMIA Acute leukemia: Acute course, with bleeding, infections Chronic leukemia: Course is chronic - years Microscopically: Acute: Primitive bone marrow cells in the bone marrow and in the blood Chronic: Relatively differentiated bone marrow cells in the blood E. MORAN

41 LEUKEMIA Burden of Suffering US 2017 est. new cases 62,000 Acute lymphocytic leukemia 6,000 Chronic lymphocytic leukemia 20,000 Acute myeloid leukemia 21,000 Chronic myeloid leukemia 9,000 Other leukemias 5,800 E. MORAN

42 Genetic factors Viral infection ACUTE LEUKEMIA Etiology Radiation exposure Chemicals exposure E. MORAN

43 LEUKEMIA Symptoms Weakness, fatigue Recurrent infections Bleeding, gum bleeding Bone pain Anorexia E. MORAN

44 A child with bleeding in the mouth mucosa had low platelets in the blood 44

45 E. MORAN

46 Petechiae in Leukemia E. MORAN

47 View of the eye fundus showing multiple spot bleeding caused by low platelets in a patient with acute leukemia 47

48 BLEEDING INTO THE BRAIN IN LEUKEMIA B/O LOW PLATELETS E. MORAN

49 E. MORAN

50 LEUKEMIA Treatment Acute leukemia (lymphatic and myeloid): Chemotherapy Bone marrow transplantation Chronic lymphatic leukemia: Chemotherapy Chronic myeloid leukemia: Chemotherapy BMT (?) Polycythemia rubra vera: Phlebotomies Chemotherapy E. MORAN

51 LYMPHOMAS 51

52 ENLARGED GLANDS (LYMPHADENOPATHY) Subjective: tender or painless Objective: Acute or chronic Local or general Isolated or matted glands Differential diagnosis: Chronic infections Cancer Diagnosis: Biopsy and pathologic examination No needle biopsy E. MORAN

53 Left cervical lymphadenopathy (Enlarged lymph nodes) Chonic lymphatic leukemia (CLL) E. MORAN

54 Right Cervical (Neck) Enlarged Lymph Nodes - Lymphoma 54

55 Burkitt s lymphoma 55

56 Relapse of Testicular Cancer On pathology review: Large cell lymphoma E. MORAN

57 Liver scan with focal areas of involvement 57

58 Abdominal CT Scan of a Patient with Lymphoma E. MORAN

59 E. MORAN

60 Lymphomas other than Hodgkin s Disease Classified by their rate of proliferation: Low-grade Intermediate grade Hi-grade E. MORAN

61 Treatment of Lymphomas Low-grade (Indolent) lymphomas: Observation Chemotherapy at time of progression +/- Radiation High-grade (aggressive) lymphomas: Chemotherapy Bone marrow transplantation E. MORAN

62 TREATMENT of LUNG CANCER 62

63 E. MORAN

64 LUNG CANCER Treatment Surgery for curative intent Surgery for palliative intent Radiation therapy Systemic chemotherapy Intra-cavitary (intra-pleural) chemotherapy E. MORAN

65 LUNG CANCER: Localized or not? E. MORAN

66 LUNG CANCER Surgery Provided that Pulmonary Function Tests (PFT s) are minimally OK one can do: Wedge resection Segmental resection of small peripheral lesions Lobectomy Pneumonectomy E. MORAN

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68 LUNG CANCER Radiation Therapy Effective as used alone or in combination with systemic chemotherapy Dose depends on the histologic type of the cancer New modalities showed increased effectiveness E. MORAN

69 E. MORAN

70 E. MORAN

71 LUNG CANCER Complications Atelectasis (collapse of lung tissue) Infection Bronchopneumonia Pleural effusion (fluid) Metastases to brain, adrenals, bones, liver Paraneoplastic syndromes with metabolic alterations E. MORAN

72 INTERMISSION 72

73 TREATMENT of PROSTATE CANCER 73

74 Prostate Needle Biopsy/ies 74

75 E. MORAN

76 Clinical Stage PROSTATE CANCER OCCULT LYMPHNODE METASTASES VS. TUMOR STAGE AND GRADE Tumor Grade (Gleason) (Localized Dis.) Well Intermediate Poor (2-4) (5-7) (8-10) % % % T1, N0, M T2, N0, M T3, N0, M E. MORAN

77 PROSTATE CANCER METASTASES 77

78 Metastatic Prostate Cancer to the Skeleton 78

79 E. MORAN

80 What should we know? Disease control - rates? Side effects? Indicated for the particular patient? Quality of life? Radical prostatectomy with removal of seminal vesicles Retropubic prostatectomy Perineal prostatectomy SURGERY Laparoscopic/robotic prostatectomy (Nerve-sparing technique and Pelvic lymph node sampling are necessary) E. MORAN

81 E. MORAN

82 E. MORAN

83 Clinically Localized Prostate Cancer Prostate cancer Intervention Versus Observation Trial (PIVOT) Study Prostatectomy vs. Observation men, mean 67 y.o. Localized prostate cancer PSA median 7.8 ng/ml Any Gleason score Follow-up 8 yrs. Conclusion: Prostatectomy did not reduce mortality rate E. MORAN

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85 E. MORAN

86 E. MORAN

87 LHRH agonists Turn off the testicle production of male hormone. Shots given q months (Lupron, Zoladex) Combined Androgen Blockade LHRH agonist + antiandrogen (Flutamide) Side effects: Decreased libido Hot flashes Breasts enlargement Loss of muscle and increase in body fat Osteoporosis Androgen Deprivation Therapy Risk of Coronary heart disease and of Type 2 diabetes E. MORAN

88 UPPER GI CANCER 88

89 Limit Alcohol and Tobacco Combination of Alcohol and Cigarettes Increases Risk for Cancer of the Esophagus 40x Risk Increase 30x 20x 10x Alcoholic Drinks Consumed per Day Packs of Cigarettes Consumed per Day AND N. C. I. 89

90 ESOPHAGEAL CANCER Symptoms Difficulty swallowing solid foods Later difficulty and pain swallowing fluids Weight loss Change in taste E. MORAN

91 Endoscopy Esophageal cancer 91

92 Cancer of the Esophagus Treatment Neo-adjuvant chemotherapy 3 months Surgery Adjuvant chemotherapy +/- radiation therapy E. MORAN

93 STOMACH 93

94 STOMACH CANCER Lack of appetite and Unexplained weight loss is a common sign of cancer. Nausea & vomiting: Sometimes the vomit may have blood in it. Stomach pain in the upper abdomen. Early satiety (Feeling full after a small meal). Heartburn. E. MORAN

95 STOMACH CANCER Treatment Surgery with dissection and removal of the satellite lymph nodes. Adjuvant chemotherapy. 5-year survival rates: 18% - 94%, depending on the stage E. MORAN

96 TREATMENT of COLORECTAL CANCER 96

97 Treatment of Colon Cancer Surgery: Surgical removal of the area involved Careful dissection of satellite lymph nodes (N1-N3 sites) Examination of the liver Chemotherapy If N+ (Stage 2) adjuvant If distant mets. (Stage 4) E. MORAN

98 E. MORAN

99 E. MORAN

100 TREATMENT of TESTICULAR CANCER 100

101 TESTICULAR CANCER Presentation Symptoms: Painless swelling in one testicle Scrotal pain (rare) Occasional: symptoms related to mets. Signs: Firm testicular nodule or mass Epididymis involvement Hydrocele E. MORAN

102 TESTICULAR CANCER Tumor Markers After orchiectomy, markers should become normal Persistent elevation = residual disease Useful in dx. of relapse (clinical f/u) E. MORAN

103 TESTICULAR CANCER Management Staging: Is the disease limited to the testicle? Chest X-ray and abdominal CT scan Biomarkers: - Alpha-Fetoprotein (AFP) - β subunit of human chorionic gonadotropin (beta-hcg) - Lactic dehydrogenase (LDH) All biomarkers must became normal after orchiectomy E. MORAN

104 Ultrasound of the Scrotum: Right Testicle Cancer Normal left testicle Seminoma in right testicle 104

105 TESTICULAR CANCER Treatment RADICAL ORCHIECTOMY (Removal of the testicle and of the spermatic cord = the only acceptable diagnostic and therapeutic procedure Retroperitoneal lymph node dissection Radiation therapy for pure seminoma Chemotherapy for extra-testicular disease E. MORAN

106 CANCER of the UTERUS 106

107 CANCER OF THE UTERUS Risk Factors Menstruating at an early age. Starting menopause at a later age. Never giving birth. Taking estrogen only (HRT) after menopause. Taking tamoxifen to prevent or treat breast cancer. Obesity and Metabolic syndrome. E. MORAN

108 CANCER OF THE UTERUS Risk Factors (cont d) Having type 2 diabetes. Having polycystic ovarian syndrome. Having a family history of endometrial cancer in a first-degree relative (mother, sister). Having certain genetic conditions, such as Lynch syndrome. Having endometrial hyperplasia. E. MORAN

109 Metabolic Syndrome. Weight 182 Kg/400 lbs., Height 6 ft. 1 in. The BMI is 53. DEFINITION: 1. ABDOMINAL OBESITY, 2. HIGH BLOOD PRESSURE, 3. HIGH BLOOD SUGAR, 4. HIGH SERUM TRIGLYCERIDE, 5. LOW HIGH-DENSITY SERUM LIPOPROTEIN (LDL) LEVEL 109

110 Cancer of the Uterus - Symptoms Irregular periods Menorrhagia Abundant blood discharge Metrorrhagia Pelvic pain E. MORAN

111 Endometrial Cancer - Ultrasound 111

112 Cancer of the Uterus - Treatment 112

113 CANCER OF THE UTERINE CERVIX 113

114 Normal Uterine Cervix 114

115 Cervical Cancer (invasive carcinoma) Cervical Cancer (Invasive Carcinoma) University of Alabama at Birmingham 115

116 CERVICAL CANCER SCREENING RECOMMENDATIONS All women who are or have been sexually active Papanicolaou (Pap.) test 3 yrs. after first vaginal intercourse and no later than 21 y.o. Pap. q. yr. in hi-risk cases After 30 y.o., if Pap. negative (x 3), screening with Pap. and HPV DNA testing q. 3 yrs. Pap. may be discontinued at 70 y.o. if previously normal E. MORAN

117 Avoid Cancer Viruses High HPV Infection Increases Risk for Cervical Cancer Cervical Cancer Risk Low Noninfected women Women infected with HPV N. C. I. 117

118 CANCER of the URINARY BLADDER 118

119 Blood in the urine Cancer of the Urinary Bladder. Symptoms are not specific Having to urinate more often than usual Pain or burning during urination Urgency = feeling that one needs to go right away, although the bladder is not full Having trouble urinating or having a weak urine stream Late symptoms: Being unable to urinate Loss of appetite and weight loss Feeling tired or weak Bone pain E. MORAN

120 BLADDER CANCER STAGES

121 LIVER, PANCREAS, and ABDOMEN 121

122 LIVER SCAN SHOWING DEFECTS E. MORAN

123 CT Scan - Metastatic cancer to the liver 123

124 Upper Abdomen Duodenum, Pancreas, and Spleen 124

125 Endoscopic retrograde cholangiopancreatography (ERCP) 125

126 PERITONEUM - SCHEMA 126

127 LAPARASCOPY (Looking into the Abdominal Space) 127

128 SKIN CANCER

129 SKIN CANCER SCREENING Risk Factors Atypical moles (dysplastic nevi) Congenital moles Large number of common moles Immunosuppression Family/personal history of skin cancer Fair skin, poor tanning ability Intense sun exposure Severe sun burns in childhood E. MORAN 2018

130 >5 million new cases in U.S. 1:5 Americans will have skin cancer >95% are basal cell or squamous cell carcinoma Organ transplant patients x 100 times more at risk 90% of non-melanoma are associated with exposure to E. MORAN 2018 SKIN CANCER SCREENING Burden of Suffering UV radiation Actinic keratosis = most common precancer ,000 new malignant melanoma cases ,700 deaths

131 Malignant melanoma vs. Benign nevi (moles) Asymmetry Borders Color Diameter changing E. MORAN 2018

132 Malignant Melanoma of the Skin 132

133 Sites of Melanoma Development 133

134 STAGES OF MELANOMA

135 Malignant melanoma Stage and Survival 100% Five-Year Survival Rates for Patients with Melanoma (by stage) 50% I II III Stage at Time of Initial Diagnosis N. C. I.

136 END OF LECTURE #4 END OF THIS CLASS THANK YOU 136