P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

Platelet function can be modified by cancer cells to support tumor growth, causing alterations in the delicate hemostatic equilibrium. Cancer-cell and platelet interactions are one of the main pillars of Trousseau’s syndrome: a paraneoplastic syndrome with recurring and migrating episodes of thrombophlebitis. Altogether, this leads to a four-fold risk of thrombotic events in cancer patients, which in turn, portend a poor prognosis. We previously demonstrated that anti-P2RY12 drugs inhibit cancer-associated-thrombosis and formation of tumor metastasis in pancreatic cancer models. Here, we aimed to (1) compare the effects of aspirin and clopidogrel on pancreatic cancer prevention, (2) characterize the effects of clopidogrel (platelet P2RY12 inhibitor) on cancer-associated thrombosis and cancer growth in vivo, (3) determine the effect of P2RY12 across different digestive-tract cancers in vitro, and (4) analyze the expression pattern of P2RY12 in two different cancer types affecting the digestive system. Clopidogrel treatment resulted in better survival rates with smaller primary tumors and less metastasis than aspirin treatment. Clopidogrel was also more effective than aspirin at dissolving spontaneous endogenous thrombi in our orthotopic advanced cancer mouse model. P2RY12 expression gives pancreatic adenocarcinomas proliferative advantages. In conclusion, we propose the hypothesis that clopidogrel should be further studied to target and prevent Trousseau’s syndrome; as well as diminish cancer growth and spread. However, more studies are required to determine the implicated pathways and effects of these drugs on cancer development.

Trousseau’s syndrome associated with an ovarian borderline tumour

A 71-year-old woman was admitted to our hospital because of sudden onset of weakness on the left side of her body. Her medical history was unremarkable, and on physical examination, hemiparesis and hyperreflexia on the left side were found. MRI of the brain showed multiple areas of restricted diffusion in both parietal lobes and in the cerebellum, consistent with embolic shower. Magnetic resonance angiography showed no abnormal findings. A contrast-enhanced CT scan revealed multiple pulmonary emboli. Abdominal MRI showed a 135 mm left ovarian tumour composed of a solid and a cystic component with liquid level formation. After a total hysterectomy and bilateral adnexectomy, the histopathology confirmed a seromucinous borderline tumour. Therefore, the patient was diagnosed with Trousseau’s syndrome associated with an ovarian seromucinous borderline tumour. To our knowledge, this is the first report mentioning a borderline ovarian tumour detected as Trousseau’s syndrome.

Left pneumonectomy for primary lung cancer with Trousseau’s syndrome

Trousseau’s syndrome is a paraneoplastic syndrome and a pathological condition that causes cerebral stroke symptoms due to hypercoagulation associated with malignant tumours. There have been many cases of advanced lung cancer, but few reports have described surgery for lung cancer with Trousseau’s syndrome. We encountered a 76-year-old man suspected of having Trousseau’s syndrome associated with lung cancer. He was transferred to our hospital on the second day after the onset. After admission, he was treated with heparin and edaravone, and his condition improved. On the 12th day after the onset, we performed left pneumonectomy and lymph node dissection (ND2a-2). The final pathological results were adenocarcinoma, pathological stage was T4 (tumour size: 77 mm, pulmonary artery invasion) N1(#11, #12u) M0, stage IIIA. He has been recurrence free for 23 months since the surgery. In the future, we need to follow his condition carefully.