Internal Medicine Half Day. July 18, 2006

Transcription

1 Internal Medicine Half Day July 18, 2006

2 Outline Pancreatic Cancer Melanoma Ovarian Cancer

3 Outline Definition Epidemiology / Risk Factors Histologic Types Presentation Staging Prognosis Treatment

4 Pancreatic Cancer

5 Definition

6 Epidemiology ~3500 new cases/y ~3400 deaths/y Male:Female 1.35:1 Peak incidence 70 s 80 s Mean incidence % metastatic at diagnosis Canadian Cancer Statistics

7 Risk Factors Smoking 1 st and 2 nd -hand Advanced age African american males Native female Hawaiians Low SES DM Chronic Pancreatitis Cirrhosis Obesity Increased height Low physical activity High fat/cholesterol diet Occupational exposure to carcinogens DeVita 7 th Edition 2005

8 Risk Factors PRSSI hmsh2 and hmlh1 (HNPCC) BRCA2 P16 (FAMM) STK11/LKB1 (Peutz( Peutz-Jeghers) ATM (Ataxia-telangiectasia telangiectasia) VHL MEN1 predominantly endocrine tumours pancreatic peptide, gastrinoma, insulinoma, GHRFoma, VIPoma DeVita 7 th Edition 2005

9 Epidemiology & Risk Factors Canadian Cancer Statistics

10 Epidemiology & Risk Factors Canadian Cancer Statistics

11 Histologic Types Solid Infiltrating ductal adenocarcinoma Acinar cell carcinoma Pancreatoblastoma Cystic Mucinous cystic neoplasm Intraductal papillary mucinous neoplasm Serous cystic neoplasm Solid pseudopapillary neoplasm

12 Histologic Types Endocrine Gastrinoma ZE syndrome Generally malignant Ulcers Insulinoma Generally benign Whipple s s triad no exogenous insulin VIPoma Sx of hypoglycema Blood glucose <2.5 Relief after ingestion of glucose Verner-Morrison syndrome Endocrine cholera WDHA watery diarrhea, hypokalemia, achlorhydria

13 Presentation Jaundice Abdominal pain Dark urine Pale stool Weight loss Weakness Anorexia Depression Back pain New onset diabetes Pancreatitis Ascites

14 Presentation Consider pancreatic cancer in patients with: Back pain with red flags Weight loss Depression Other symptoms would prompt a CT or U/S anyways.

15 Work-up Hx Px Labs CA 19-9 LFT s CBC Imaging CT MRI

16 Staging TNM Tumour (T) T1 limited to pancreas; < 2cm T2 limited to pancreas; > 2cm T3 out of pancreas but not celiac/sma T4 out of pancreas but into celiac/sma Nodes (N) N0 negative nodes N1 regional nodes Metastases (M) M0 no metastases M1 distant metastasis AJCC 6 th Ed.

17 Staging Stage T N M IA IB IIA IIB III IV any 0 any any 1 Surgery and Chemo Chemo AJCC 6 th Ed.

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19 ROYAL COLLEGE INTERLUDE For almost all tumours stage is the most important prognostic factor Written question Female undergoes radical mastectomy and axillary dissection. Pathology shows infiltrating ductal carcinoma. What is the most important factor for prognosis? Tumor of 4 cm 6/14 positive nodes estrogen status age of the patient

20 ROYAL COLLEGE INTERLUDE Female undergoes radical mastectomy and axillary dissection. Pathology shows infiltrating ductal carcinoma. What is the most important factor for prognosis? Tumor of 4 cm 6/14 positive nodes estrogen status age of the patient The bottom line is that all are prognostic factors. Nodal status plays a bigger role in staging so it s s B. B

21 Prognosis Chart Data

22 Prognosis Median Survival Stage III 8-12 months Stage IV 3-66 months

23 Treatment Surgery Radical Palliative Radiation Radical/Adjuvant Palliative Chemotherapy Adjuvant Neoadjuvant Palliative

24 Surgery Stage I-IIBI IIB Pancreaticoduodenectomy (Whipple s) For tumours of the head, neck or uncinate process Distal Pancreatectomy Stage III-IV IV Internal biliary bypass Choledochojejunostomy Choledochoduodenostomy cholecystojejunostomy

25 Surgery Whipple s s Procedure

26 Surgery - Palliative Stent insertion ERCP Obstructive jaundice EGD Gastric outlet obstruction

27 Radiation Mostly for palliative intent Can be combined with chemo (5-FU, gemcitabine or paclitaxel) Survival increases from to months for Stage III

28 Chemotherapy Neoadjuvant Prior to surgery Gemcitabine plus paclitaxel has been used to successfully downstage No clear benefit Consider chemoradiation Try to improve resectability Clinical trial preferred NCCN Guidelines v

29 Chemotherapy Adjuvant Following surgery Chemoradiation 5FU +/- gemcitabine Chemotherapy alone Gemcitabine Benefit from chemotherapy 5FU + RT 2y OS 43% Control group 2y OS 18% NCCN Guidelines v

30 Chemotherapy Locally Advanced Unresectable 5FU + RT +/- gemcitabine Gemcitabine alone Metastatic Goals are palliation and improved survival Gemcitabine relatively mild Response rate 23% Median survival 5.6 vs. 4.4 months 1y survival 18% vs. 2% Relief of symptoms Burris et al JCO 1997;

31 Similar Tumours Cholangiocarcinoma Not quite as bad as pancreatic cancer Treated similarly Adenocarcinoma of the Ampulla of Vater Not quite as bad as cholangiocarcinoma or pancreatic cancer Treated similarly

32 Questions??

33 Melanoma

34 Definition

35 Epidemiology & Risk Factors ~4500 new cases/y Incidence is on the rise (fastest rise in incidence except lung cancer in women) Male:Female 3:2 ~880 deaths/y Ranks second in potential years of life lost Canadian Cancer Statistics

36 Epidemiology & Risk Factors Canadian Cancer Statistics

37 Epidemiology & Risk Factors Canadian Cancer Statistics

38 Risk Factors Family history Dysplastic nevi Fair skin easy sunburn Sun exposure NCCN Guidelines v

39 Histologic Types Superficial spreading melanoma Nodular melanoma Lentigo maligna melanoma Acral lentiginous melanoma Desmoplastic melanoma Epithelioid melanoma Spindle cell melanoma Balloon cell melanoma Malignant blue nevus NCCN Guidelines v

40 Presentation Skin lesion Ulceration Itch Bleeding lesion Screening

41 Work-up Hx Px Examine closely for lymphadenopathy Complete skin exam Labs CBC Chemistry, LFT s,, LDH Imaging As needed Definitely if lymph nodes are involved Body cavity adjacent to the involved nodes CT/MRI brain if any symptoms whatsoever

42 Staging Clarke s s Level I (epidermis) II (papillary dermis) III (filling papillary dermis) IV (reticular dermis) V (subcutaneous)

43 Staging Breslow s Level < 0.75 mm mm mm > 4.0 mm Actual depth of invasion is recorded

44 Staging - TNM T1 < 1mm A = no ulceration; B = ulceration T2 1-2mm T3 2-4mm T4 > 4mm N1 = positive nodes A = microscopic; B = macroscopic; C = satellite M = distant mets NCCN Guidelines v

45 Staging - TNM Stage T N M IA IB IIA IIB IIC 1a 0 0 1b 0 0 2a 0 0 2b 0 0 3a 0 0 3b 0 0 4a 0 0 4b 0 0 III any IV any any 1 Surgery Chemo? surgery NCCN Guidelines v

46 Prognosis

47 Treatment Surgery Excisional biopsy (0.5-2cm margins) Margins depend on depth of invasion Sentinal Lymph Node Dissection If depth > 1mm For solitary metastatic deposits Radiation For metastatic lesions

48 Treatment Chemotherapy Adjuvant Consider interferon alpha-2b No consistent improved survival Metastatic or Recurrent (RR ~20%) small survival advantage duration of response ~ 4 months DTIC temozolomide High dose interleukin-2

49 ROYAL COLLEGE INTERLUDE Management of Brain Metastases Woman presents 5 years after removal of a Clarke s s stage 4 malignant melanoma on her thorax. Has seizure. Frontal lobe mass. What do you do? Focal RT Chemotherapy Surgical excision and whole brain RT Stereotactic bx and focal RT

50 ROYAL COLLEGE INTERLUDE Woman presents 5 years after removal of a Clarke s stage 4 malignant melanoma on her thorax. Has seizure. Frontal lobe mass. What do you do? Focal RTX CTX Surgical excision and whole brain RTX Stereotactic bx and focal RTX Median survival with brain mets 3.5 months Median survival after metastasectomy 8 months Consider Gamma Knife + WBRT

51 Questions?

52 Ovarian Cancer

53 Definition

54 Epidemiology & Risk Factors ~2300 new cases/y ~1600 deaths/y Increased incidence with age Peak prevalence 80 s Mean age at diagnosis 63 70% present with advanced disease Canadian Cancer Statistics NCCN guidelines v

55 Epidemiology & Risk Factors Canadian Cancer Statistics

56 Epidemiology & Risk Factors Canadian Cancer Statistics

57 Epidemiology & Risk Factors Risk factors Decreased Risk 30-60% RRR Give birth before age 25 Oral contraceptive use Breastfeeding Increased Risk Nulliparity First birth older than 35 2 or more first degree relatives*** BRCA1 & 2 NCCN Guidelines v

58 Histologic Types Epithelial Ovarian Cancer Papillary serous** Endometrioid Mucinous Clear Cell Germ Cell Teratoma Dysgerminoma Choriocarcinoma Sex Cord Stromal Metastatic deposits Krukenberg (metastatic signet ring carcinoma)

59 Presentation Abdominal bloating/distension Abdominal discomfort Vaginal bleeding GI symptoms GU symptoms Symptoms of excess estrogen or androgen Amenorrhea Bleeding virilization

60 Work-up Hx Px including pelvic Labs CBC Chemistry/LFT LFT s CA 125 Imaging CT U/S

61 Staging - FIGO T1 T2 T3 Tumour limited to ovaries 1A one ovary, 1B both; 1C through capsule or malignant ascites Pelvic extension - ABC Peritoneal metastases ABC (size)

62 Staging - FIGO Stage T N M IA IB IC IIA IIB IIC IIIA IIIB IIIC IV 1a 0 0 1b 0 0 1c 0 0 2a 0 0 2b 0 0 2c 0 0 3a 0 0 3b 0 0 3c or 1 0 any any 1 Surgery and Chemo Surgery

63 Prognosis

64 Treatment Surgery Staging Debulking TAH BSO Chemotherapy Carboplatin + Paclitaxel Intraperitoneal cisplatin

65 Treatment

66 ROYAL COLLEGE INTERLUDE Malignant Ascites Woman with malignant ascites.. What type of cancer would be most amenable to treatment? ovarian colon breast lung

67 ROYAL COLLEGE INTERLUDE Woman with malignant ascites.. What type of cancer would be most amenable to treatment? ovarian colon breast lung

68 Questions?