A 75-year-old man with a prior history of adenocarcinoma of the prostate treated with radical prostatectomy presents with pain in the left hip. The pain awakens him at night and has become increasingly severe over the previous 3 weeks. Plain radiographs show numerous bilateral osteoblastic lesions in the hip and sacrum, and the prostatespecific antigen level is 83 µg/mL (normal 0-4).
Which of the following is the treatment of choice?
Patients with metastatic prostatic carcinoma are treated with endocrine therapy to shrink primary and secondary lesions by depriving prostatic tissue of circulating androgens. Estrogens are no longer recommended because of the high incidence of cardiovascular events. Most patients now receive a GnRH analogue or surgical castration; whether an antiandrogen (such as flutamide) provides additional benefit is currently a matter of debate. The bisphosphonate zoledronic acid can decrease pain and skeletal-related complications in patients with bony metastases and may be added to hormonal therapy. Radiotherapy is used for localized disease, but is less effective than hormonal therapy. The survival benefit of chemotherapy, if any, is small.
A 73-year-old woman is admitted for deep venous thrombosis and concern for pulmonary embolism. She has a history of type 2 diabetes mellitus, hypertension, and coronary artery disease. She had been admitted for a three-vessel coronary artery bypass graft 2 weeks prior to this admission. She did well and was dismissed 5 days after the procedure. Pain and swelling of the right leg began 2 days before this admission; she has noticed mild dyspnea but no chest pain. The clinical suspicion of deep vein thrombosis (DVT) is confirmed by a venous Doppler, and the patient is started on unfractionated heparin. Her initial laboratory studies, including CBC, are normal. The next day her pain has improved, and helical CT scan of the chest reveals no evidence of pulmonary embolism. She is instructed in the use of low-molecular-weight heparin and warfarin; she is eager to go home. Her serum creatinine is normal. Her predischarge CBC shows no anemia, but the platelet count has dropped to 74,000. An assay for antibodies to heparin-platelet factor 4 complexes is ordered.
What is the best next step in her management?
Heparin is the commonest cause of drug-induced thrombocytopenia. Between 10% and 15% of patients receiving unfractionated heparin develop thrombocytopenia. The drop in platelet count is attributed to the production of an antibody against a complex of heparin and platelet factor 4. Lowmolecular-weight heparin can also cause thrombocytopenia, although less frequently than unfractionated heparin. Usually the platelet count drops 5 to 10 days after heparin is started. In this case, however, the patient likely had been exposed to heparin at the time of her CABG. With previous exposure, the thrombocytopenia can begin within hours of the reinstitution of any form of heparin. Although low-molecular-weight heparin causes HIT less frequently than unfractionated heparin, all heparin products must be discontinued in the patient with HIT. In all patients with an active clot and those with HITT (heparin-induced thrombocytopenia with thrombosis), a direct thrombin inhibitor must be started and used as a bridge to full-potency warfarin therapy. The chief consequence of HIT is not bleeding but accelerated clotting resulting from the aggregation of platelet-heparin complexes in the circulation. HITT is a feared complication of HIT. Even with proper treatment, the amputation rate (owing to intra-arterial clotting) is as high as 40%, and the death rate as high as 25%.
A 26-year-old healthy man comes to your clinic for an annual wellness examination. He does not take any medications. He smokes ½ pack of cigarettes daily. He tells you that his father died of colon cancer at the age of 45. He also has a 25-year-old cousin who recently had colonoscopy for rectal bleeding was found to have multiple polyps and is scheduled for total colectomy. Your patient wants to know if he can inherit colon cancer and if there is a way to find out if he is at risk. You talk to him about how some cancers can be caused by genetic mutations.
For what genetic mutation is this patient at highest risk?
Familial adenomatous polyposis (FAP) is characterized by the appearance of thousands of adenomatous polyps throughout the large bowel. It is transmitted as an autosomal dominant trait. It is associated with a deletion in the long arm of chromosome 5, which contains the APC gene. The colonic polyps are usually evident by age 25. If untreated, patients usually develop colon cancer by the age of 40. Once multiple polyps are detected, patients should undergo a total colectomy, which is the primary therapy to prevent colon cancer. Current guidelines recommend that patients with a family history of FAP should have screening with flexible sigmoidoscopy or colonoscopy beginning at the age of 25, followed by annual screening until age 35. An alternative method for identifying carriers is testing peripheral blood mononuclear cell DNA for the presence of a mutated APC gene. The detection of this mutation can lead to a definitive diagnosis before the development of polyps. The MEN 1 gene is associated with multiple endocrine neoplasia type 1, which does not increase the risk of colon cancer. The RET gene is associated with multiple endocrine neoplasia type 2. The MSH gene is associated with hereditary non-polyposis colon cancer (HNPCC), also known as Lynch syndrome. In contrast to FAP, patients with HNPCC or Lynch syndrome do not develop multiple polyps but instead develop only one or a few adenomas that rapidly progress to cancer. This condition is also strongly associated with ovarian and endometrial carcinoma. The BRCA gene is associated with familial breast and ovarian cancers.
A patient with bacterial endocarditis develops thrombophlebitis while hospitalized. His course in the hospital is uncomplicated. On discharge he is treated with penicillin, rifampin, and warfarin. Therapeutic prothrombin levels are obtained on 15 mg/d of warfarin. After 2 weeks, the penicillin and rifampin are discontinued.
Which of the following is the best next step in management of this patient?
Rifampin induces the cyto-chrome P450 that metabolizes warfarin; higher doses of warfarin are required to overcome this effect. When rifampin is stopped, the dose of warfarin necessary to produce a therapeutic prothrombin time will decrease. Barbiturates also accelerate the metabolism of warfarin. Many drugs interfere with the metabolism and clearance of warfarin. Drugs such as nonsteroidal anti-inflammatories can compete with warfarin for albumin-binding sites and will lead to an increased prothrombin time. The list of medications that can either increase or decrease the effect of warfarin is long; all patients given this drug should be advised to contact their physician before taking any new drug. They should also be counseled about over-the-counter drugs (aspirin and NSAIDs) and even health food supplements (such as ginkgo biloba) which can affect the prothrombin time in these patients. A stable intake of vitamin K–containing foods (ie, green leafy vegetables) is recommended.
A 65-year-old man with diabetes mellitus, bronzed skin, and cirrhosis of the liver is being treated for hemochromatosis previously confirmed by liver biopsy. The patient experiences increasing right upper quadrant pain, and his serum alkaline phosphatase is now elevated. There is a 15-lb weight loss.
Which of the following is the best next step in management?
Patients with hemochromatosis and cirrhosis have a very high incidence of hepatocellular carcinoma. The lifetime incidence of this complication is 30% and increases with age. Weight loss and abdominal pain suggest hepatocellular carcinoma in this patient. A CT scan or ultrasound and measurement of α-fetoprotein are indicated. The picture of right upper quadrant pain and elevated alkaline phosphatase would not suggest acute hepatitis (which causes an elevation of transaminases) or worsening of the cirrhosis caused by hemochromatosis. Primary biliary cirrhosis (associated with antimitochondrial antibodies) can cause obstructive biliary disease, but would be much less likely in this patient.
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