ΔΙΑΓΝΩΣΤΙΚΗ ΚΑΙ ΘΕΡΑΠΕΥΤΙΚΗ ΠΡΟΣΕΓΓΙΣΗ ΑΣΘΕΝΩΝ ΜΕ ΚΑΡΚΙΝΟ

USA 2015

MULTISTAGE CARCINOGENESIS

INVASION AND METASTASIS

TUMOR GROWTH number of cancer cells 10 12 10 9 diagnostic threshold (1cm) time undetectable cancer detectable cancer limit of clinical detection host death

ΣΥΜΠΤΩΜΑΤΑ ΑΠΟ ΤΟΝ ΚΑΡΚΙΝΟ 1. Τοπική δράση σε ιστούς & όργανα 2. Παρανεοπλασματικές εκδηλώσεις

Διάγνωση Σταδιοποίηση Θεραπευτική Αντιμετώπιση

ΚΑΡΚΙΝΟΣ : ΜΕΘΟΔΟΙ ΔΙΑΓΝΩΣΗΣ & ΣΤΑΔΙΟΠΟΙΗΣΗΣ 1. Ιστορικό 2. Φυσική εξέταση 3. Απεικονιστικές μέθοδοι 4. Ενδοσκοπήσεις ( κυτταρολογική βιοψία ) 5. Ανοικτή βιοψία, FNA, Pap test 6. Εργαστηριακές εξετάσεις

BREAST CANCER/LOCAL MANIFESTATIONS Signs and symptoms at presentation Palpable mass Thickening Pain Mass or pain in the axilla Nipple discharge Nipple retraction Edema or erythema of the skin

BREAST CANCER Breast inspection Skin dimpling

BREAST CANCER Breast palpation

BREAST CANCER Regional nodes assessment

BREAST CANCER Spread to lymph nodes Supraclavicular Subclavicular Distal (upper) axillary Mediastinal Internal mammary Central (middle) axillary Proximal (lower) axillary Interpectoral (Rotter s)

BREAST CANCER Fine-needle aspiration biopsy In Out Suction End Suction Back and Forth

BREAST CANCER/DISTANT MANIFESTATIONS Signs and symptoms at presentation Lymph nodes Brain Skin Pulmonary Liver Kidney Bone

TNM CLASSIFICATION Tumor Nodes Metastasis Good Bad Prognosis

BREAST CANCER Stage IV disease Any T any N M1 M1 = Distant metastasis (including metastases to ipsilateral supraclavicular, cervical, or contralateral internal mammary lymph nodes)

BREAST CANCER Distal spread Brain + Skin + Lung + + + Pleura + + + Liver + + Adrenals + + Bone + + + +

BREAST CANCER Survival by stage Percent surviving 100 80 60 40 20 Stage 0 Stage I Stage IIA Stage IIB Stage IIIA Stage IIIB 0 1 2 3 4 5 6 Years after diagnosis Stage IV

BREAST CANCER Survival according to the number of positive nodes Percent Surviving 100 80 60 40 Number of positive nodes 0 1 2-3 4-5 6-10 11-15 16-20 21 or more 20 0 1 2 3 4 5 Years after diagnosis Adapted from Wilson RE et al, 1994

PRIMARY BREAST CANCER Good prognostic factors Patient s age: Axillary nodes: Size of tumor: Local extension of tumor: older than 50 years not involved small (< 1 cm) absent Histologic examination: well-differentiated tumor (grade I) Cytologic study: little atypia of nuclei (grade I) Estrogen Progesterone receptors: positive (ER + and PR +) Oncogene amplification: absent

PRIMARY BREAST CANCER Poor prognostic factors Patient s age: Axillary nodes: Size of tumor: Local extension of tumor: Histologic examination: Cytologic study: 35 40 years involved large (>5 cm) present anaplastic tumor (grade III) severe atypia of nuclei (grade III) Estrogen Progesterone receptors: negative (ER and PR ) HER2 Oncogene amplification: present

LUNG CANCER Signs and symptoms at diagnosis FREQUENCY (%) 75 50 40 40 40 30 25 35 25 40 35 35 15 15 15 15 COUGH DYSPNEA CHEST PAIN HEMOPTYSIS PNEUMONITIS WEIGHT LOSS GENERALIZED ANOREXIA FEVER ANEMIA WEAKNESS

LUNG CANCER Paraneoplastic syndromes SMALL CELL LARGE CELL SQUAMOUS ADENOCARCINOMA Inappropriate ADH secretion Ectopic ACTH production Gynecomastia Eaton-Lambert Hypercalcemia (nonmetastatic) Hypertrophic osteoarthropathy Thrombocytosis Hypercoagulable stage +++ +++ ++ ++ ++ ++ + +++ +++ ++ ++ +++ ++ ++ +++ ++ ++

LUNG CANCER Incidence of major histologic types 33% 25% 25% 16% 1% EPIDERMOID CARCINOMA ADENOCARCINOMA LARGE-CELL CARCINOMA SMALL-CELL CARCINOMA OTHERS (Bronchoalveolar mixed)

LUNG CANCER HISTOLOGIC TYPES Smokers vs nonsmokers 38 56 SQUAMOUS CELL ADENOCARCINOMA LARGE CELL SMALL CELL BRONCHOALVEOLAR 35 68 27 23 23 21 22 17 13 11 10 9 10 6 5 1 3 2 SMOKER (%) NONSMOKER (%) SMOKER (%) NONSMOKER (%) MALE FEMALE Adapted from Rosenow and Carr

LUNG CANCER Local and distal spread Brain Draining lymph nodes Liver Adrenals Bone

NON SMALL CELL LUNG CANCER Split by stages 37% 28% 15% 10% 10% T1 N0 T1 N1 T2 N0 T2 N1 IIIA Resectable IIIA Partially Resectable IIIB Unresectable Adapted from a lung cancer group survey

COLON Anatomic segments and vascular supply Transverse colon Hepatic flexure Mid. colic a. Sup. mes a. and v. Inf. mes. v. Splenic flexure R. colic a. Ascending colon Inf. mes. a. L colic a. Descending colon Cecum small intestine Sup hemorrhoidal a. and v. Aorta Sigmoid colon RIGHT LEFT Middle hemorrhoidal a. Rectum Internal pudenda a. Inferior hemorrhoidal a.

COLORECTAL CANCER Pretreatment evaluation HISTORY Including familial history of CRC/polyps/other cancers PHYSICAL EXAMINATION Digital examination of the rectum Hepatomegaly/ascites/lymphadenopathies In women: breast/ovarian abnormalities LABORATORY DATA Blood count, CEA, liver chemistry GASTROINTESTINAL EXAMINATION Full colonoscopy IMAGING Chest X-ray Abdominal ultrasound for colon cancer Abdominal pelvic CT scan for rectal cancer Other CT scans as appropriate (metastases) --- MRI, etc if needed

COLORECTAL CANCER Symptomatology and evolution 1) EARLY STAGES No symptoms Abdominal pain Flatulence Minor changes in bowel movements Rectal bleeding Anemia 2) LATE STAGE LEFT-SIDE COLON Constipation or diarrhea Abdominal pain (colicky pain) Obstructive symptoms (nausea/vomiting) 3) LATE STAGE RIGHT-SIDE COLON Vague abdominal aching Anemia (iron loss by chronic microscopic bleeding) Weakness Weight loss 4) LATE STAGE RECTUM Change in bowel movements Rectal fullness Urgency Bleeding Tenesmus Pelvic pain (later stage)

COLORECTAL CANCER Symptoms and their frequency Pain Changes in bowel movements Weakness 7% 40% 36% 25.5% 65% 78% Compared frequency of clinical symptomatology of colon cancer (from 180 cancers) Anemia 0.8% 11% Bleeding 7% 88% Abdominal mass Occlusion 0% 6.5% 1.6% 7% Right-side colon cancer Left-side colon cancer Adapted from Metman EH, Bertrand J, Bouleau PH. Rev Prat. 1979; 29(13):1077-1088.

COLORECTAL CANCER TNM classification, definition of T (primary tumor) Tis T 1 T 2 T 3 T 4 Mucosa Muscularis mucosae Submucosa Muscularis propria Subserosa Serosa Extension to an adjacent organ

COLORECTAL CANCER Usual prognostic factors Prognostic factor Bad prognosis Stage TNM III-IV Age <40 years Performance status WHO >2 Symptoms + Duration of symptoms <6 months Obstruction/perforation + Location of primary tumor Rectum/rectosigmoid Histopathology Mucinous (colloid) and signet-ring adenocarcinomas LDH CEA/Other biomarkers Ploidy >5 ng/ml Aneuploidy

COLORECTAL CANCER 5-year postsurgery follow-up guidelines Procedure/Test Frequency Comment History/examination Every 3-4 mo for 2y and then every 6 mo for 3y Detects one third of recurrences Colonoscopy Chest X-ray CEA Liver (US) } Liver chemistries CT scans (chest, abdo, pelvic) Other scans (liver, spleen, bone) Preoperatively or 4-6 mo postoperatively, then every 6-36 mo Every 6 mo Every 2-4 mo for 2y then every 6 mo for 2y Same As indicated by findings on history, examination, or elevated CEA levels Every 3 years after free of polyps CEA, serum carcinoembryonic antigen; CT, computed tomography; US, ultrasound

COLORECTAL CANCER Sites and frequency of distant metastases Liver 38-60% Abdominal lymph nodes 39% Lung 38% Peritoneum28% Ovary 18% Adrenal glands 14% Pleura 11% Brain 8% Bone 10% Adapted from: Kemeny N, Seiter K. Colon and rectal carcinoma. In: Handbook of chemotherapy in clinical oncology. SCI ed.1993:589-594.

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