Mesothelioma

Question 1

4 locations for mesothelioma in dogs?

Answer 1

thoracic cavity, abdominal cavity, pericardial sac, scrotum

Question 2

4 locations of mesothelioma in cats?

Common location for metastasis?

Answer 2

pericardium, pleura, peritoneum, abdomen

w/ mets to lungs and mediastinal lymph nodes

Question 3

What is a contributing factor for mesothelioma?

Answer 3

asbestos

Question 4

How does asbestos lead to development of mesothelioma?

Answer 4

Cancer develops through direct and indirect contact with asbestos and through chronic inflammation which creates an immunosuppressive microenvironment (myeloid-derived suppressor cells, tumor-associated mac’s, and T-regs)

Question 5

Common mutations in mesothelioma?

Answer 5

tumor suppressors cyclin dependent kinase inhibitor 2A (CDKN2A), BRCA1 associated protein 1 (BAP1) and neurofibromin 2 (NF2)

Question 6

What is a promoting cytokine in mesothelioma?

Answer 6

Promoting cytokines include VEGF from stimulated macrophages or mesothelioma cells

Question 7

4 characteristics of normal mesothelial cells?

Answer 7

Normal mesothelial cells: (1) monolayer; (2) microvilli; (3) desmosomes; (4) phagocytic capacity

Question 8

What is sclerosing mesothelioma?

Answer 8

Specific subtype that resembles sarcoma, with GSD over-represented

Question 9

Cystic mesothelioma (reported in 1 dog) is localized and treated with surgery in humans

Question 10

Effusion occurs due to?

Answer 10

blocked lymphatics or tumor exudate

Question 11

Sclerosing mesothelioma produces a thick fibrous lining that restricts and impinges on organs – presents with vomiting and/or urinary tract signs

Question 12

Dogs with neoplasia tend to have thickening of the _____ only compared to dogs with inflammatory effusions and CT evidence of chest wall invasion is specific for neoplasia

Answer 12

parietal pleura

Question 13

Pleural effusion elevation in _____ is sensitive but not specific; however, if _____ levels are NOT INCREASED, then mesothelioma can be ruled out

Answer 13

fibronectin

Question 14

What is necessary for diagnosis?

Answer 14

Biopsy of cavity lining (and regional LN)

Question 15

In humans the most common markers are calretinin, Wilm’s tumor gene (WT1), cytokeratin 5/6 (CK5/6), and D2-40, but 30% of tumors are “null” phenotype expressing none of these

Question 16

Treatment for dogs with tamponade?

Answer 16

Pericardectomy

Question 17

MST with sx alone?

Sx and chemo?

Answer 17

SX alone survival 4-9 months

5 dogs - Sx (+ 2 DOX, 1 MITOX) MST 13.9mo

1 dog - Pericardectomy + IV DOX + IP Cisplatin à 27mo

8 dogs – partial pericardectomy à 15-300 days

The dog that lived 300 days had IV DOX and IP Cisplatin for the final 4 months

Question 18

Thorascopic partial pericardectomy reported; one dog had seeding at the thorascopic portal site

25% complication rate; 7% mortality rate; short hospital stays (1 day)

Median DFI in and MST in dogs treated with thorascopy vs thoracotomy did not differ (3-4mo)

Placement of a permanent port aids in palliation and chemotherapy infusion

Question 19

Intracavitary cisplatin is palliative and generally well tolerated (3 dogs had decrease in effusion)

Intracavitary carboplatin in a cat – 2 doses - decreased effusion, resolution of cx signs for 54 days

Local penetration of chemotherapy is 2-3mm; can combine with debulking Sx or IV DOX

Question 20

Peritoneal mesothelioma:

Piroxicam (0.3mg/kg SID) + 4 doses IP cisplatin (dog) or carboplatin (cat) à all had resolution cx signs; 2+ years one dogs that also had debulking sx; 8mo in another dog and 6 months in cat both of which had 90% fluid reduction – Spugnini 2008

Question 21

Comparative

70-80% of mesotheliomas in humans linked to occupational exposure (long latency period 12-50yrs)

Less common exposure to natural substances with shorter latencies

Human MST 1year with tx

First line therapy = platinum drug + raltitrexed or pemetrexed (anti-metabolites)