No abstract

Preference is given to letters commenting on contributions published recently in the JRSM. They should not exceed 300 words and should be typed double-spaced Adenocarcinoma of the gallbladderWe read with interest the 5-year review of outcome by Burgess et al. (February 1991 JRSM, p 84). The authors remind us of the dismal results of treatment of this uncommon disease. Publications concerning this neoplasm are few and it is likely that surgeons confronted with such a case would look to the above article for management guidance.The authors state 'There is probably a place for routine adjuvant local radiotherapy in addition to surgery'. The statement is referenced but unfortunately, perhaps due to a typographical error, it is not printed at the end of the article with the other citations.We do not think that routine postoperative radiotherapy for invasive or in-situ carcinoma of the gallbladder represents a statement of the conventional wisdom within the radiotherapeutic community. It would be useful if the authors could expand upon their statement and produce the missing reference.

4665 Introduction: Multiple sclerosis (MS) is an autoimmune inflammatory and chronic demyelinating disease. Occurrence of hypercoagulable states and breast cancer in patients with multiple sclerosis (MS) has not been extensively reported. We report a case of a female MS patient with recurrent DVTs, elevated factor VIII levels, and advanced breast cancer with aggressive biologic phenotypes. Case report: A 45-year-old Caucasian female with a history of MS had a breast mass diagnosed on a screening mammogram. She was diagnosed with right breast carcinoma (2.5 × 2.5 × 1.6 cm), T2 N3 M0, which correlated to stage IIIC. She underwent a right modified radical mastectomy with 16/25 lymph nodes involved, ER/PR status was positive, HER-2/neu 0 with high Ki67. Her post-surgery treatment plan included 4 cycles of Cyclophosphamide and Taxotere chemotherapy. She also received chest wall radiation as well as tamoxifen and aromatase inhibitor (Femara) therapy. The patient had never been on hormone replacement therapy or oral contraceptives. She had bilateral salpingo-oophorectomy and hysterectomy and pathology was unremarkable. Patient was diagnosed with Multiple Sclerosis at age 27. She was treated with intermittent courses of steroids, Interferon b-1b, Interferon b-1a, and Mitoxantrone (MTX) for relapsing/remitting MS for several years until she developed left hemiparesis, hypoesthesias, and residual visual dysfunction that prompted her to start IVIG therapy and plasmapheresis. Past medical history presents recurrent DVT (in 2006) and elevations of coagulation factor VIII (355%). The patient also developed superior vena cava thrombosis in the presence of Lovenox and coumadin therapy. Discussion: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system, frequently complicated by devastating neurologic symptoms and progressive disability. Risks of DVT in bedridden or wheelchair-bound MS patients have been suggested. Previous studies show that the frequency of DVT in late-stage MS may be over 40%. Additionally, in MS patients without risk factors, it has been suggested with an autoimmune inflammatory disease that the inflammatory infiltration in MS plaques located close to small or medium-sized veins could have a role as well. The lumbar puncture could also be one of other thrombophilic factor in MS, since after dural puncture the decrease of cerebrospinal fluid pressure induces a rostrocaudal sagging effect with traumatic damage to the fragile venous endothelial wall and may trigger a venous vasodilatation with resultant stasis. Elevated factor VIII levels are a risk factor for venous thrombosis and may also be associated with the risk of arterial thrombosis in coronary heart disease. Studies show that factor VIII levels may be increased by chronic inflammation. However, elevated factor VIII levels in patients with MS have never been reported. There is no cure for MS, though there are several drugs such as immunomodulatory agents that can slow or stop its progress. However, current data show a small increased risk of breast cancer in women with MS. The size of the breast tumor was also larger for woman with MS. More specifically, the proportions of biologically aggressive phenotypes that can worsen the prognosis of breast cancer incrementally despite the biologic phenotype at diagnosis also were investigated in this group of patients. One hypothesis linking breast cancer and MS involves long-term use of immunomodulatory agents including IFNs and glatiramer. Immunomodulatory therapy may impart immune system alterations that promote enhancement of cancer cells’ ability to evade immune recognition and cancer metastasis by altering the body’s ability to conduce immunosurveillance. However, consistent with previous observations, this remains unexplained and warrants further attention. Conclusion: The Female patient with MS described in this article presents an example of recurrent DVT, Superior Vena Cava thrombosis, elevated factor VIII levels, and breast cancer with stage IIIC and biologically aggressive phenotypes. The authors concern is that there is an increased risk of hypercoagulation states and breast cancer development in patients with MS. The systematic application of long-term preventive DVT may be considered for this group of patients. Disclosures: No relevant conflicts of interest to declare.

4663 Background Stroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. The incidence of cerebrovascular accident (CVA) in young adults has been increasing. Since the etiology of CVA in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report 2 cases of ischemic stoke in young adults with multiple risk factors. Case Report No. 1. A 46-year-old male presented to the ER with loss of consciousness. Past medical history was unremarkable. MRA confirmed occlusion of the left posterior cerebral artery. Transesophageal Echocardiogram (TEE) revealed a patent foramen ovale (PFO) and atrial septal aneurysm (ASA). Hypercoagulable evaluation confirmed increased IgM anticardiolipin antibody, a lupus anticoagulant, and heterozygous MTHFR (Methylenetetrahydrofolate reductase) C677T mutation. Anticoagulation therapy was started with Heparin and then switched to Coumadin. Aspirin was also initiated along with folic acid, Vitamin B6 and B12, and smoking cessation therapy. Unfortunately, the patient developed hemiparesis and dementia after stroke. No. 2. A 50-year-old female presented to the ER with headache and blurred vision for one hour. Patient had cerebrovascular accident (CVA) 7 years prior to that event. She has been taking aspirin. MRI confirmed encephalomalacia in the left cerebellar hemisphere. TEE revealed a PFO. During the PFO closure procedure, an atrioseptal defect and a myxomatous were diagnosed. Patient was directed to use clopidogrel for at least six months after procedure, and aspirin indefinitely. Discussion The differential diagnosis for potential etiology in young people (under 55 years of age) of CVA is broader than that for older adults. Ischemic strokes are much more common than hemorrhagic in this group of patients. The atypical causes are more prevalent in the younger population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease needs to be considered. Cardiogenic cerebral embolus is the most common cause of stroke in young adults. Stroke can be associated with abnormalities of the atrial septum, specifically PFO, atrial septal defect (ASD), aneurysm, and cardiac myxomas. Studies show that the prevalence of PFO in patients who have stroke of unknown cause (cryptogenic stroke) may be about 40 percent. More specifically, PFO increases the rate of paradoxical thromboembolic stroke that occurs by allowing blood clots from the venous system to enter the arterial system. This is particularly true in patients who have had a stroke at an age less than 55 years. PFO closure procedures may help to identify underlying causes of CVA, as was discussed in case 2. Some studies have described an association between atrial septal aneurysm (ASA) and embolic strokes. The embolus might originate in an ASA or from a clot around the edges of a PFO. The mechanism of cerebrovascular events with ASA may be platelet/thrombus formation at the site of the aneurysm. Aspirin may be effective therapy for preventing CVA. Emboli from cardiac myxomas also can lead to cerebral ischemia, infarction, and aneurysm formation. Up to half of cardiac myxomas produce systemic emboli. Consequently, studies show that inherited thrombophilic disorders in the pathogenesis of stroke might relate to congenital heart diseases. The data suggests that Factor V Leiden G1691A mutation or Prothrombin G20210A variant may be associated with PFO. An increased prevalence of right-to-left shunts in patients with cerebrovascular accident CVA and activated protein C resistance has also been documented. Antiphospholipid Antibody Syndromes (APS) are recognized as independent risks for Cerebrovascular Accident (CVA). APS are associated with a heterogeneous group of disorders that result in hypercoagulable states involving arterial and venous thrombosis. Cerebral circulation is particularly affected in APS. Conclusion Based on these observations, the authors conclude that hypercoagulable testing should be performed in young patients with CVA. In addition, PFO closure procedures may be an important diagnostic tool that helps to identify a subset of patients in whom the etiology of CVA was not apparent. Disclosures: No relevant conflicts of interest to declare.