Practical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixaban.

The new oral anticoagulants dabigatran etexilate (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many physicians are wary of these drugs, since there is limited evidence on how to manage bleeding in patients taking them, and since no specific antidote is known to reverse their anticoagulant effect. Management requires careful adherence to first principles of bleeding care. Unapproved and untested reversal strategies may be required in patients with life-threatening bleeding.

Mai infection simulating metastatic breast cancer.

We represent a case of an asymptomatic female who was found to have a mass in the right breast which confirmed an invasive ductal carcinoma by core biopsy. After 3 months of completion of chemo-radiotherapy, the patient remained totally asymptomatic. However, positron emission tomography scan showed four hypermetabolic lesions in the left lung thought to be consistent with metastatic disease. Standard uptake value ranged between 3.86 and 6; the results were consistent with metastatic breast cancer, so wedge resection was performed. Caseating granulomatous inflammation with necrosis was reported. Ultimately culture revealed Mycobacterium avium intracellulare infection. The lesions resolved completely after a course of antibiotics.

Hepatitis B reactivation in cancer patients: role of prechemotherapy screening and antiviral prophylaxis.

Hepatitis B virus (HBV) infection is a potentially life-threatening condition that can be effectively prevented by vaccination. In the United States, more than 1.5 million people are infected with HBV, and that number continues to rise with the arrival of immigrants from HBV-endemic countries. Cancer is the second leading cause of death in the United States; 1 in 2 men and women will be diagnosed during their lifetime, and a large proportion of them will require chemotherapy. Chemotherapy-induced immunosuppression can result in HBV reactivation in asymptomatic HBV carriers or patients with resolved HBV infection, causing severe morbidity and mortality. The rate of HBV reactivation depends on several factors, including host and viral factors, and varies from 3-88%. Mortality rates in HBV reactivation range from 23-71%. However, a recent US survey showed that 20% of practicing oncologists never perform any type of HBV screening before the initiation of chemotherapy, and less than 40% perform HBV screening in patients who have high-risk factors for HBV or a history of hepatitis. Given the magnitude of this clinical problem, it is very important to increase awareness among physicians regarding this potentially life-threatening complication. In this article, we review the current understanding of the problem, discuss the existing guidelines from professional societies, and outline a management plan.

Constipation in Clostridium difficile infection.

A patient presented to our hospital with worsening shortness of breath, cough and respiratory distress that slowly worsened over 7-10 days. She had a viral-like illness with runny nose and cough for 1 week, which became productive of yellowish sputum. She was treated with antibiotic and steroid with clinical improvement. Her leucocyte count continued to increase despite discontinuation of both antibiotic and steroid. All culture results returned negative. She did not have any abdominal pain or diarrhoea. Her stool was positive for Clostridium difficile toxin assayed by PCR. A CT of abdomen showed distension of cecum and proximal colon. She was treated with intravenous metronidazole, oral and rectal vancomycin and intravenous immunoglobulin. She developed multi-organ failure and died.

Pleomorphic malignant histiocytoma: a rare skin cancer in a patient on azathioprine for ulcerative colitis.

A 67-year-old female who was diagnosed with ulcerative colitis in 2001, presented with a soft tissue mass in the middle of her back of 4 months duration in April 2011. It was excised; however it recurred at the same site in September 2011. Wide excision of the mass was done. Pathology revealed T1aNxM0 pleomorphic malignant fibrous histiocytoma or undifferentiated pleomorphic sarcoma. Whole body bones scan and staging CT scan of the chest, abdomen and pelvis was negative for distant metastasis. She received local radiotherapy at the site of excision. No chemotherapy was given.

Rituximab-induced bronchiolitis obliterans organizing pneumonia.

Rituximab-induced lung disease (R-ILD) is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough, but no clear evidence of infection. A variety of pathologic findings have been described in this setting. Bronchiolitis obliterans organizing pneumonia (BOOP) is the most common clinicopathologic diagnosis, followed by interstitial pneumonitis, acute respiratory distress syndrome (ARDS), and hypersensitivity pneumonitis. Prompt diagnosis and treatment with corticosteroids are essential as discussed by Wagner et al. (2007). Here we present a case of an 82-year-old man who was treated with rituximab for recurrent marginal zone lymphoma. After the first infusion of rituximab, he reported fever, chills, and dyspnea. On computed tomography imaging, he was found to have bilateral patchy infiltrates, consistent with BOOP on biopsy. In our patient, BOOP was caused by single-agent rituximab, in the first week after the first infusion of rituximab. We reviewed the relevant literature to clarify the different presentations and characteristics of R-ILD and raise awareness of this relatively overlooked entity.

BOOP as a rare complication of gemcitabine therapy.

Gemcitabine is commonly used in combination with carboplatin in patients with advanced non-small-cell lung cancer (NSCLC). Gemcitabine has good clinical activity against NSCLC and is well tolerated by the patients. Myelosuppression is its dose-limiting toxicity. A potential side effect of gemcitabine is pulmonary toxicity. Among pulmonary toxicities, pneumonia, bronchospasm, acute respiratory distress syndrome, pleural effusion and interstitial pneumonitis are well documented, but bronchiolitis obliterans organising pneumonia (BOOP) is a rarely observed adverse effect of gemcitabine therapy. The authors report a female patient who presented with progressively worsening shortness of breath, low-grade fever and non-productive cough 10 days after completion of gemcitabine therapy for poorly differentiated invasive squamous cell carcinoma of lung with bone metastases. Histopathology of a transbronchial biopsy established the diagnosis of BOOP. Treatment with intravenous steroids resulted in prompt clinical improvement, but the patient later died of progression of her lung cancer.

Haematuria as an uncommon initial presenting symptom of metastatic squamous cell carcinoma (SCC) to kidney.

A 47-year-old female presented with a 2-week history of painless haematuria. Urine dipstick showed moderate leucocytes. Blood and urine cultures were negative and cytology was negative for malignant cells. Flexible cystoscopy was negative for any bladder pathology. An ultrasonogram of the abdomen showed a mass in the left kidney. CT showed a mass-like lesion within the left kidney suspicious for renal carcinoma, and cavitary lesions in both lungs. Biopsy of the lung showed clusters of atypical cells suspicious for squamous cell carcinoma (SCC), and left kidney lesion showed malignant cells derived from SCC. A whole body positron emission tomography/CT showed lesions in the lungs, left kidney and skeleton. Complete clinical examination, laboratory and imaging studies did not reveal any site of primary tumour in any part of the body. Haematuria is a very unusual initial presentation of metastatic tumour to kidney.

Pulmonary toxicities of tyrosine kinase inhibitors.

The incidence of pulmonary toxicities with the use of tyrosine kinase inhibitors (TKIs) is not very high; however, various case reports and studies continue to show significant variability in the incidence of these adverse events, ranging from 0.2% to 10.9%. Gefitinib and erlotinib are orally active, small-molecule inhibitors of the epidermal growth factor receptor tyrosine kinase that are mainly used to treat non-small cell lung cancer. Imatinib is an inhibitor of BCR-ABL tyrosine kinase that is used to treat various leukemias, gastrointestinal stromal tumors, and other cancers. In this article, we review data to identify the very rare but fatal pulmonary toxicities (mostly interstitial lung disease) caused by these drugs.

Pulmonary toxicities of biologics: a review.

With the advancement of research in cancer treatment more and more drugs are being introduced for the treatment of cancer. In this review study, we have tried to look at some of the relatively newly introduced drugs, commonly referred to as biologics. The aim of this study was to review the very rare but fatal pulmonary toxicities (mostly interstitial lung disease) caused by these drugs. The drugs that were reviewed are rituximab, cetuximab, bevacizumab, alemtuzumab, and trastuzumab. This review basically aims at presenting a basic introduction (mechanism of action and indications of use) of these drugs followed by a summary of the incidence, various clinical presentations, diagnosis, treatment options, and outcome of patients around the world who presented with pulmonary toxicities caused by these drugs.

Hepatic iron overload, a possible consequence of treatment with imatinib mesylate: a case report.

Imatinib, a tyrosine kinase inhibitor has revolutionized the therapy of Philadelphia chromosome positive chronic myeloid leukemia. Side effects of imatinib include grade 1-4 hepatotoxicity in a subset of patients. We report the case of a 46-year-old male with chronic myeloid leukemia, who developed hepatic hemosiderosis during treatment with imatinib. After ruling out the established congenital and acquired causes of hepatic hemosiderosis, we attribute this to a possible side effect of imatinib therapy. This condition was successfully treated with periodic phlebotomy thus precluding discontinuation of imatinib. To our knowledge, this is the first report of hepatic hemosiderosis most likely consequent to imatinib therapy.

A renal mass in a patient with melanoma.

A 61-year-old man presented to the emergency room with significant weight loss. Laboratory analysis revealed elevations in blood urea nitrogen, creatinine, and white blood cell count. Computed tomography imaging showed a large, infiltrative mass in the right renal vein, with metastasis to the brain. Biopsy of soft tissue mass and kidney revealed positive staining for malignant melanoma. Malignant melanoma to the kidney is extremely rare, and imaging modalities alone cannot differentiate neoplasms in the kidney. It is therefore necessary to use specific immunocytochemical staining along with imaging modalities to make a specific diagnosis when the primary origin of the tumor is unknown.

Venous thromboembolism in lymphoma: how effectively are we treating patients?

INTRODUCTION: Patients with solid tumors and venous thromboembolic episodes (VTE) have a high risk of recurrence and bleeding during oral anticoagulant treatment. However, we are unaware of studies expressly evaluating such risks in patients with lymphoma. Therefore, we conducted a retrospective study to determine the frequency of such complications during treatment of lymphoma patients who develop VTE. METHODS: Charts of patients with histologically proven non-Hodgkin lymphoma and Hodgkin lymphoma were retrospectively reviewed and patients with their first acute symptomatic VTE episode were identified (49 non-Hodgkin lymphoma, 8 Hodgkin lymphoma). Recurrence of VTE episodes and major and minor bleeding during treatment with warfarin or low molecular weight heparin (LMWH) were recorded. RESULTS: All 57 patients were initially treated with high-dose-adjusted intravenous heparin or body-weight-adjusted LMWH. Forty-six patients were started on oral warfarin and 11 patients continued LMWH. Recurrent VTE episodes occurred in 14 of 46 patients on warfarin therapy, whereas major bleeding was documented in 6 of 46 patients, and minor bleeding in 9 of 46 patients. Recurrent VTE episodes occurred in 1 of 11 patients treated with LMWH, whereas major bleeding occurred in 0 of 11 and minor bleeding in 3 of 11 patients. CONCLUSIONS: Lymphoma patients treated with warfarin experienced a 30.4% rate of recurrent thrombosis and 13% major bleeding. During this treatment most (65%), but not all, bleeding and thrombotic complications occurred with an international normalized ratio within the therapeutic range. The percentage of serious complications (recurrent VTE and major bleeding) during warfarin use was 44.5%, and the death rate was 6.5%, compared with 9% and 0%, respectively, during use of LMWH.

Aromatase inhibitor-related musculoskeletal symptoms: is preventing osteoporosis the key to eliminating these symptoms?

BACKGROUND: Aromatase inhibitors (AIs) are an effective treatment for postmenopausal women with hormone receptor-positive breast cancer. However, patients receiving AIs report a higher incidence of musculoskeletal symptoms and bone fractures; the mechanism and risk factors for this correlation are not well studied. The aim of this study was to correlate these musculoskeletal symptoms and bone fractures in patients receiving AIs with bone mineral density (BMD), previous tamoxifen use, and administration of calcium/bisphosphonate (Ca/Bis). PATIENTS AND METHODS: We reviewed charts of 856 patients with hormone receptor-positive nonmetastatic breast cancer seen at our institution between January 1999 and October 2007. A total of 316 patients met the inclusion criteria of treatment with one of the AIs for > or = 3 months and availability of a dualenergy X-ray absorptiometry (DEXA) during this treatment. Arthralgia, generalized bone pain and/or myalgia, bone fracture after beginning AIs, any tamoxifen treatment, and Ca/Bis therapy were recorded. RESULTS: Our study demonstrates a significant association between symptoms and DEXA-BMD results (P < .001). Similarly, the group receiving tamoxifen before AIs had fewer patients with arthralgia or generalized bone pain/myalgia or bone fracture (P < .001). Furthermore, the group receiving AIs plus Ca/Bis had more patients without musculoskeletal symptoms and had fewer fractures. Finally, the group receiving steroidal AIs compared with nonsteroidal AIs had more patients with arthralgia or generalized bone pain and/or myalgia, and bone fractures (P < .001). CONCLUSION: Patients on AIs who develop osteoporosis are at increased risk of musculoskeletal symptoms and bone fracture. Comedication with Ca/Bis reduces the likelihood for osteoporosis and musculoskeletal symptoms. Patients who received tamoxifen before AIs were less likely to develop AI-related musculoskeletal symptoms. We recommend that patients on AIs should be offered Ca/Bis to reduce the incidence of musculoskeletal symptoms and fracture, especially if patients are receiving steroidal AI and/or did not receive tamoxifen before AIs.