Gurpreet Lamba

Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis

BackgroundLiposomal formulations of anthracyclines appear to have favorable toxicity profile when compared with conventional anthracyclines in elderly, high risk cardiac patients and patients with prior use of anthracyclines. Randomized controlled trials have evaluated the efficacy and safety profile of liposomal formulations with conventional anthracyclines. Our aim is to evaluate the adverse effects and quantify the relative safety profile of the liposomal and conventional anthracyclines through meta-analysis of the published randomized trials.MethodsWe conducted a broad search strategy of major electronic databases. We performed a meta- analysis of adverse effects on randomized controlled trials comparing liposomal formulation and conventional anthracyclines on different tumors. The primary outcome was the adverse effects including congestive heart failure (CHF), hematological toxicity, palmar-plantar erythrodysthesias (PPE), alopecia, nausea and vomiting. The odds ratios of the adverse effects were calculated separately and the overall odds ratio of the pooled data was calculated.ResultsWe identified nine randomized controlled trials comparing liposomal formulations and conventional anthracyclines. The study included 2220 patients, of which1112 patients were treated with liposomal formulations and 1108 were treated with conventional anthracyclines. We found that the liposomal formulations have low incidence of CHF(OR 0.34, 95% CI, 0.24–0.47), alopecia (OR 0.0.25, 95% CI, 0.0.10-0.62), neutropenia (OR 0.62, 95% CI, 0.45- 0.85),(OR 0.89, 95% CI, 0.71-1.125), and thrombocytopenia (OR 0.87, 95% CI, 0.61-1.25). The incidence of PPE was similar in both arms (OR 1.08, 95% CI, 0.11- 10.30).ConclusionsLiposomal doxorubicin and pegylated liposomal doxorubicin demonstrated favorable toxicity profiles with better cardiac safety and less myelosuppression, alopecia, nausea and vomiting compared with the conventional anthracyclines. The better therapeutic index of liposomal anthracyclines without compromising the efficacy makes it a favorable choice over conventional anthracyclines in elderly patients, patients with risk factors for cardiac disease and patients with prior use of anthracyclines.

Current management and prognostic features for gastrointestinal stromal tumor (GIST)

Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI) tract have undergone a remarkable evolution in how they are perceived, classified, approached, diagnosed and managed over the last 30 years. Gastrointestinal stromal tumors (GIST) account for approximately 1% to 3% of all malignant GI tumors. The clinical features can vary depending on the anatomic location, size and aggressiveness of the tumor. Metastatic GIST represents a successful example of molecular targeted therapy. In this comprehensive review, we discuss the epidemiology, clinical features and diagnostic modalities for GIST. We also describe treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with duration of therapy are also explained. A brief discussion of latest biomarkers and updates from recent meetings is also provided.

Recent advances and novel agents for gastrointestinal stromal tumor (GIST)

The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone. Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative. GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic “driver” pathways, leading to dramatically improved clinical outcomes. A series of investigations and trials are underway to develop novel and effective ways to treat patients with GIST. In this review, we discuss the highlights of recent advances and novel agents for GIST therapy.

Psoriasis induced by losartan therapy: a case report and review of the literature.

Psoriasis is a papulosquamous disease of multifactorial etiology. A combination of genetic and environmental agents is implicated in its pathogenesis. A variety of triggers, including infection, stress, and medications, have been recognized as precipitants of this disease. Nonsteroidal anti-inflammatory drugs, beta-blockers, lithium, synthetic antimalarials, and gold are the most common drugs implicated in precipitating psoriasis. We report a patient with psoriasis induced by initiation of losartan therapy, which resolved with discontinuation of the drug. The Naranjo adverse drug reaction probability scale score indicated that the association between losartan use and psoriasis was probable.

Recent advances and novel agents for FLT3 mutated acute myeloid leukemia

Acute myeloid leukemia (AML) is a devastating hematologic malignancy that affects both older adults as well as children. Treatments available for AML largely depend on cytotoxic agents and often the only curative option is an allogeneic bone marrow transplant, an option limited to young persons and associated with high morbidity and mortality. There is an urgent need for the identification of new myeloid targets and an understanding of the key genetic mutations involved in disease progression and prognosis. One such mutation is the internal tandem duplication (ITD) in the FMS-like tyrosine kinase receptor-3 (FLT3) gene which confers an inferior outcome that is attributed to a higher relapse rate. In this review, we evaluate the FLT3-ITD mutation and discuss the recent data regarding emerging approaches using FLT3 inhibitors for the treatment of AML.

Use of Conjugated Estrogens in Life-Threatening Gastrointestinal Bleeding in Hemodialysis Patients—A Review

Hormonal agents (estrogen and progesterone) are being studied for their use in bleeding. This observance was initially explored in a patient with hereditary hemorrhagic telangiectasia (HHT) with epistaxis had variation in bleeding depending on her menstrual cycles.1 Thus, hormonal therapy was initially used in patients with HHT to control episodes of epistaxis.2 The literature on hormonal therapy in patients with life-threatening bleeding from gastrointestinal (GI) lesions is very limited. There are a few clinical trials in patients with chronic bleeds. However, no definite guidelines exist on their use in life-threatening GI bleeding in patients with uremia. Here, we describe a case with a life-threatening GI bleeding requiring multiple endoscopies and intensive care unit stay that responded to conjugated estrogens. We have done extensive research on English medical literature on PubMed and Google Scholar on the use of hormonal therapy for GI bleeding in patients with renal failure, and here we present the data as a review.

Sunitinib and Thrombosis.

Sunitinib is a multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006 [1]. Sunitinib inhibits cellular signaling by targeting multiple RTKs including platelet-derived growth factor and vascular endothelial growth factor receptors, which play a role in both tumor angiogenesis and tumor cell proliferation. The simultaneous inhibition of these targets leads to reduced tumor vascularization, cancer cell death, and ultimately tumor shrinkage. This multi-targeted inhibition is also believed to be responsible for increased risk of arterial thromboembolism previously reported by Choueri and colleagues [2]. We present the first case with both arterial and venous thrombosis in a patient treated with sunitinib. Case Report

Superior Mesenteric Vein Thrombosis Following Treatment of Refractory Immune Thrombocytopenic Purpura with Romiplostim

Romiplostim is a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in patients with chronic idiopathic thrombocytopenic purpura (ITP) who had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Although thrombotic and embolic complications have been reported in patients receiving romiplostim, these have generally involved coronary artery or cerebral vascular events. Currently we report a patient with severe ITP treated with romiplostim who developed mesenteric venous thrombosis after a hemicolectomy to resect colon cancer.

Colonic perforation secondary to chronic lymphocytic leukemia infiltration without Richter transformation

The World Health Organization classification of hematopoietic neoplasms describes chronic lymphocytic leukemia (CLL) as a leukemic, lymphocytic lymphoma, being distinguishable from small lymphocytic leukemia (SLL) only by its leukemic appearance [1]. CLL is always a disease of neoplastic B cells and is rarely associated with gastrointestinal (GI) manifestations. When this does occur, lymphocytic infiltration of the GI tract seems to depend on the tumor burden and proliferation activity [2]. Some of the reported manifestations include intussusception [3], small intestinal bacterial contamination [4], colitis [5], and others (Table I). Usually, GI complications with CLL occur after Richter transformation. Our patient showed that intestinal manifestations can appear even without this transformation. In 2005, Lalani et al. reported a case for CLL causing GI perforation [6]. In our extensive research using PubMed, we did not find any other reports or series of CLL causing a GI perforation. We believe our case is the second ever reported of the same. In this article we review the diagnosis and indications to treat CLL. We also summarize the various GI manifestations of CLL and outcomes of patients with these complications. An 86-year-old female with a history of hypertension, glaucoma, and CLL presented to our emergency room (ER) with dizziness and left eye blurry vision for 2 days. CLL had initially been diagnosed 4.5 years previously with peripheral blood flow cytometry, and was Rai stage 0. At the time of diagnosis her white blood cell (WBC) count was 29 000 cells/mL with an absolute lymphocyte count of 24 000 cells/mL without anemia or thrombocytopenia. Over the next 4.5 years her WBC count gradually increased to 207 000 cells/mL and was monitored closely. Now she presented with nausea and vomiting as well as the dizziness and left eye blurry vision. This was associated with a weight loss of approximately 5 lb, bilateral leg swelling, and occasional generalized joint pains and aches over the last 2 months. She denied any fever, chills, chest pain, or dyspnea at the time. Her WBC count in the ER was 762 000 cells/mL with a hemoglobin of 10.9 g/dL and platelet count of 124 000 cells/mL. Her absolute lymphocyte count was 265 000 cells/mL and lactate dehydrogenase was 205 IU/L. Treatment was initiated with leukapheresis and chemotherapy with cyclophosphamide, fludarabine, and hydroxyurea. On the following day, she developed mild abdominal pain with an episode of hypotension. An urgent computed tomography (CT) scan of the abdomen and pelvis showed acute sigmoid diverticulitis with perforation and free intra-abdominal air. The patient underwent emergent explorative laparotomy and colostomy placement. Pathology review showed a perforated diverticulum and an intramural abcess with multifocal transmural uniform small lymphocytic infiltration of the sigmoid colon. A fibroadipose tissue specimen also revealed multifocal uniform small lymphocytic infiltration and one focus of large lymphoid aggregate with monotonous small lymphocytes. After an unremarkable postoperative hospital course, the patient was discharged to a