1. SYB Case 3 By: Amy

2. History 55 y/o male 55 y/o male Presented with epigastric pain in Nov 2007 Presented with epigastric pain in Nov 2007 CT/MRI of abdomen and additional workup was negative CT/MRI of abdomen and additional workup was negative Endoscopy revealed a gastric ulcer  treated Endoscopy revealed a gastric ulcer  treated Then presented twice in August 2008 with recurrent abdominal pain, was given vicoden, and was told to f/u with his primary care doc Then presented twice in August 2008 with recurrent abdominal pain, was given vicoden, and was told to f/u with his primary care doc PMHx includes Afib and PE for which he takes coumadin; pt is a smoker PMHx includes Afib and PE for which he takes coumadin; pt is a smoker CT of Abdomen performed on 9/5/08 CT of Abdomen performed on 9/5/08

4. Liver mets and a mass in body of pancreas

5. Additional history Underwent liver biopsy on 9/5/08, which showed for malignant cells consistent with adenocarcinoma  diagnosed with metastatic adenocarcinoma of the pancreas Underwent liver biopsy on 9/5/08, which showed for malignant cells consistent with adenocarcinoma  diagnosed with metastatic adenocarcinoma of the pancreas Started on systemic chemotherapy of gemcitabine with Tarceva on 9/12/08 Started on systemic chemotherapy of gemcitabine with Tarceva on 9/12/08 Because of the liver biopsy, his Coumadin was stopped and he subsequently developed bilateral leg DVTs  placed back on coumadin Because of the liver biopsy, his Coumadin was stopped and he subsequently developed bilateral leg DVTs  placed back on coumadin Repeat CT to determine response to therapy on 1/23/09 Repeat CT to determine response to therapy on 1/23/09

6. Is the patient’s disease responding well to chemo?

7. Liver mets increasing in size and number, pancreatic mass, and probable splenic infarct No; there has been significant interval progression of the liver mets and main pancreatic tumor.

9. Lytic mets to spine at T11 with mild compression of the vertebral body Hepatic fluid collection

11. Thrombus in the apex of the left ventricle

13. Renal cysts, IVC filter, and infrarenal AAA with thrombus

14. Pancreatic cancer Cancer of the exocrine pancreas is the 4th leading cause of cancer-related death in the U.S. Cancer of the exocrine pancreas is the 4th leading cause of cancer-related death in the U.S. The dx is typically made radiographically and histologically The dx is typically made radiographically and histologically Surgical resection is the only potentially curative treatment Surgical resection is the only potentially curative treatment Because of the late-presentation in many patients, only 15- 20% of patients are candidates for pancreatectomy Because of the late-presentation in many patients, only 15- 20% of patients are candidates for pancreatectomy Prognosis is often poor even in those pts with potentially resectable disease Prognosis is often poor even in those pts with potentially resectable disease There is a particularly high incidence of thromboembolic (both venous and arterial) events, particularly in the setting of advanced disease There is a particularly high incidence of thromboembolic (both venous and arterial) events, particularly in the setting of advanced disease

15. Imaging for Pancreatic Cancer Ultrasound – usually performed in pts presenting with jaundice; dilated bile ducts or a mass in the head of the pancreas are seen Ultrasound – usually performed in pts presenting with jaundice; dilated bile ducts or a mass in the head of the pancreas are seen CT and CT angiography – better sensitivity (85-90%) and similar specificity (90-95%) to US, particularly useful in pts who are not jaundiced; usually see bile and pancreatic duct dilation, a mass lesion in the pancreas, and/or extrapancreatic mets CT and CT angiography – better sensitivity (85-90%) and similar specificity (90-95%) to US, particularly useful in pts who are not jaundiced; usually see bile and pancreatic duct dilation, a mass lesion in the pancreas, and/or extrapancreatic mets Contrast is better for staging Contrast is better for staging CT angiogram can provide information about major vessel involvement (i.e. portal vein, SMA, and SMV) that may indicate surgical unresectability CT angiogram can provide information about major vessel involvement (i.e. portal vein, SMA, and SMV) that may indicate surgical unresectability ERCP – sensitivity and specificity are 90-95%; most useful if CT or US does not reveal a mass lesion or if chronic pancreatitis is in the DDx; findings include strictures or obstruction of the common bile and pancreatic ducts (“double duct” sign), and absence of chronic pancreatitis changes ERCP – sensitivity and specificity are 90-95%; most useful if CT or US does not reveal a mass lesion or if chronic pancreatitis is in the DDx; findings include strictures or obstruction of the common bile and pancreatic ducts (“double duct” sign), and absence of chronic pancreatitis changes Endoscopic ultrasound – operator-dependent; most useful for a dx of small tumors (>2-3 cm diameter) and evaluation of nodal and major vascular involvement (except for the SMA and SMV); also allows for biopsy and staging Endoscopic ultrasound – operator-dependent; most useful for a dx of small tumors (>2-3 cm diameter) and evaluation of nodal and major vascular involvement (except for the SMA and SMV); also allows for biopsy and staging MRI and MRCP – routine MRI has no significant diagnostic advantage over contrast enhanced CT for staging; therefore, the choice of MRI or CT depends on the clinician’s preference; helical CT angiography is usually preferred to MRI alone MRI and MRCP – routine MRI has no significant diagnostic advantage over contrast enhanced CT for staging; therefore, the choice of MRI or CT depends on the clinician’s preference; helical CT angiography is usually preferred to MRI alone MRCP is better than CT for defining the anatomy of the biliary tree and pancreatic duct, has the capability to evaluate the bile ducts both above and below a stricture, and can identify intrahepatic mass lesions; is also does not require contrast MRCP is better than CT for defining the anatomy of the biliary tree and pancreatic duct, has the capability to evaluate the bile ducts both above and below a stricture, and can identify intrahepatic mass lesions; is also does not require contrast MRCP is preferred to ERCP in pts with bile duct obstruction due to chronic pancreatitis and in pts in whom ERCP was unsuccessful MRCP is preferred to ERCP in pts with bile duct obstruction due to chronic pancreatitis and in pts in whom ERCP was unsuccessful

16. Thrombosis in cancer Cancer causes a hypercoagulable state Cancer causes a hypercoagulable state Cancer pts often have multiple comorbidities as well, including hospitalizations, immobilization, surgery, advanced age, metastatic disease, presence of a central venous catheter, and chemotherapy (including gemcitabine as in this patient) Cancer pts often have multiple comorbidities as well, including hospitalizations, immobilization, surgery, advanced age, metastatic disease, presence of a central venous catheter, and chemotherapy (including gemcitabine as in this patient) Thrombotic episodes may precede the dx of malignancy by months or years Thrombotic episodes may precede the dx of malignancy by months or years Particularly true for carcinomas of the GI tract, ovaries, prostate, and lung Particularly true for carcinomas of the GI tract, ovaries, prostate, and lung Can present in many different ways, including Trousseau’s syndrome, idiopathic DVT, nonbacterial thrombotic endocarditis, DIC, thrombotic microangiopathy (i.e. hemolytic-uremic syndrome), or arterial thrombosis Can present in many different ways, including Trousseau’s syndrome, idiopathic DVT, nonbacterial thrombotic endocarditis, DIC, thrombotic microangiopathy (i.e. hemolytic-uremic syndrome), or arterial thrombosis Clinical thromboembolism is the second leading cause of death in pts with overt malignant disease Clinical thromboembolism is the second leading cause of death in pts with overt malignant disease In one study, 30% of pts who died of pancreatic cancer had evidence of thrombosis In one study, 30% of pts who died of pancreatic cancer had evidence of thrombosis 50% of pts with pancreatic cancer in the body or tail had evidence of thrombosis 50% of pts with pancreatic cancer in the body or tail had evidence of thrombosis

17. Thrombosis in cancer Trousseau’s syndrome (migratory superficial thrombophlebitis) Trousseau’s syndrome (migratory superficial thrombophlebitis) Rare variant of venous thrombosis characterized by a recurrent and migratory pattern and involvement of superficial veins, frequently in unusual sites such as the arm or chest Rare variant of venous thrombosis characterized by a recurrent and migratory pattern and involvement of superficial veins, frequently in unusual sites such as the arm or chest The pt usually has an occult tumor which is not always detectable at the time of presentation The pt usually has an occult tumor which is not always detectable at the time of presentation The tumor us usually an adenocarcinoma when discovered The tumor us usually an adenocarcinoma when discovered Most common tumors in pts with this syndrome are pancreas (24%), lung (20%), prostate, stomach, acute leukemia, and colon Most common tumors in pts with this syndrome are pancreas (24%), lung (20%), prostate, stomach, acute leukemia, and colon Treatment is difficult because Coumadin appears to have no effect, while heparin can relieve some of the manifestations Treatment is difficult because Coumadin appears to have no effect, while heparin can relieve some of the manifestations Venous thromboembolism risk Venous thromboembolism risk Increased in pts with malignancy, particularly with distant metastases Increased in pts with malignancy, particularly with distant metastases Highest risk in pts with hematologic malignancies, lung, GI tract, brain, kidney, and breast cancers Highest risk in pts with hematologic malignancies, lung, GI tract, brain, kidney, and breast cancers Risk is highest in the first 3 months following a dx of malignancy and decreases after that period of time Risk is highest in the first 3 months following a dx of malignancy and decreases after that period of time VTE at least one year after the dx of a malignancy may indicate a second malignancy VTE at least one year after the dx of a malignancy may indicate a second malignancy

18. What to do? There is an absence of prospective studies demonstrating cost-effectiveness or improved survival with aggressive diagnostic testing for malignancy in patients with idiopathic DVT’s There is an absence of prospective studies demonstrating cost-effectiveness or improved survival with aggressive diagnostic testing for malignancy in patients with idiopathic DVT’s Therefore, at this time, only a careful history, physical exam (including rectal and pelvic exams), and routine lab testing (i.e. CBC, lytes, calcium creatinine, LFT’s, UA, chest radiograph, and PSA in men over age 50) should be performed Therefore, at this time, only a careful history, physical exam (including rectal and pelvic exams), and routine lab testing (i.e. CBC, lytes, calcium creatinine, LFT’s, UA, chest radiograph, and PSA in men over age 50) should be performed Any abnormalities on these tests should then be more thoroughly evaluated Any abnormalities on these tests should then be more thoroughly evaluated However, pts who present with recurrent idiopathic DVT’s represent a high-risk group and an aggressive search for malignancy should be undertaken in these patients However, pts who present with recurrent idiopathic DVT’s represent a high-risk group and an aggressive search for malignancy should be undertaken in these patients

19. References UpToDate; all accessed 1/26/09 UpToDate; all accessed 1/26/09 Bauer, K. Drug-induced thrombosis and vascular disease in patients with malignancy. Bauer, K. Drug-induced thrombosis and vascular disease in patients with malignancy. Bauer, K. Hypercoagulable disorders associated with malignancy. Bauer, K. Hypercoagulable disorders associated with malignancy. Steer, M. Clinical manifestations, diagnosis, and surgical staging of exocrine pancreatic cancer. Steer, M. Clinical manifestations, diagnosis, and surgical staging of exocrine pancreatic cancer.