Michael Maroules

Colorectal Cancer: Histopathologic Differences in Tumor Characteristics Between Patients With and Without Diabetes

BACKGROUND Current literature suggests that diabetes is a possible predictor of risk and worse outcome in colorectal cancer (CRC). The objective of this study was to explore if there are histopathologic differences in CRC between populations with and without diabetes. PATIENTS AND METHODS Retrospective analysis was done on 534 patients with CRC. Patients were divided into diabetic and nondiabetic subgroups. Data were collected for lymphovascular invasion, tumor location, depth invasion, staging, level of differentiation, histologic type, and presence of tumor components (mucinous, signet ring, or neuroendocrine). RESULTS Univariately, patients with diabetes had deeper tumor invasion, greater lymphovascular invasion, and higher TNM staging (OR and 95% CI, 2.06 [1.37, 3.10], 2.52 [1.74, 3.63], and 2.45 [1.70, 3.52], respectively; P < .001). Covariate adjustment retained the significant effect of diabetes on tumor characteristics (P < .005). Multivariable adjustment significantly linked diabetes with signet ring cell carcinoma (log odds, 11.40 ± 5.28; P = .03) and tumor components (log odds, 0.58 ± 0.25; P = .02). Patients with diabetes with hyperlipidemia had more well-differentiated tumors (log odds, -0.96 ± 0.47; P = .04). Transverse tumors were more common in patients with diabetes (log odds, 1.74 ± 0.72; P = .02). CONCLUSION Patients with diabetes had worse histopathologic CRC features. Hyperinsulinemia, insulinlike growth factor receptor activation, and hyperglycemia in diabetes can activate mitogenic pathways stimulating proliferation, invasion, angiogenesis, and metastasis. Future research is needed to identify responsible pathways for targeted therapy and to examine the role of better glycemic control and treatment in patients with CRC and diabetes.

Does an Elevated Serum Vitamin B12 Level Mask Actual Vitamin B12 Deficiency in Myeloproliferative Disorders

Elevation of the methylmalonic acid level is a sensitive marker of vitamin B(12) deficiency. Our cross-sectional observational study of 33 patients with myeloproliferative disorders found that 9 patients, 27.27% had occult deficiency despite having normal to elevated serum vitamin B(12) levels. Early detection of vitamin B(12) deficiency by using the methylmalonic acid measurement may prevent significant neurologic and hematologic complications in patients with myeloproliferative disorders. In patients with myeloproliferative disorders, normal to high serum vitamin B(12) concentrations have often been reported. The primary objective of this study was to determine whether normal or elevated serum vitamin B(12) levels in myeloproliferative disorders might actually mask the true underlying vitamin B(12) deficiency in some patients. Thirty-three patients (12 men, 21 women; mean age, 70.55 years [range, 37-90 years]) with polycythemia vera (n = 13), essential thrombocythemia (n = 12), chronic myelogenous leukemia (n = 5), and idiopathic myelofibrosis (IMF) (n = 3) were accrued over a period of 1 year, from March 2009 to February 2010. From all of the subjects, serum vitamin B(12) level, methylmalonic acid level, a basic complete blood cell count panel, and liver and renal function tests were obtained. Normal to elevated serum vitamin B(12) levels were recorded in all the patients. However, elevated serum methylmalonic acid levels were found in 9 (27.27%) patients, with a prevalence of 2 patients with polycythemia vera, 23% in polycythemia vera, 4 patients with essential thrombocythemia, 33.3% in essential thrombocythemia, 1 patient with chronic myelogenous leukemia, 20% in chronic myelogenous leukemia, and 2 patients with idiopathic myelofibrosis, 66.7% in IMF. Our data suggest that 27.27% of the total enrolled patients had occult vitamin B(12) deficiency despite normal to elevated vitamin B(12) levels on regular serum vitamin B(12) testing.

Severe hemophagocytic lymphohistiocytosis as a complication of drug-induced hypersensitivity syndrome

60 International Journal of Critical Illness and Injury Science | Vol. 5 | Issue 1 | Jan-Mar 2015 Dear Editor, Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis is a rare but fatal condition caused by inappropriate activation of macrophages against one’s blood cells and characterized by histiocyte proliferation and hemophagocytosis, resulting in fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, liver dysfunction, and coagulopathy. This condition is usually secondary to infection, autoimmune disorder, or malignancy.[1] Here, we present a rare case of severe HPS as a complication of drug‐induced hypersensitivity syndrome in a previously healthy patient.

Successful treatment of severe thrombocytopenia with the use of thrombopoeitin receptor agonist eltrombopag in a patient with chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoietic stem cells often occurring in elderly patients. The combination of CMML with autoimmune manifestations, including immune-mediated thrombocytopenia, has been described before in a number of case reports. To our knowledge, this is the first reported case of the successful treatment of CMML-related thrombocytopenia with a thrombopoeitin receptor agonist, eltrombopag.

A rare case of gastric Crohn's disease associated with immune thrombocytopenic purpura

Dear Sir, Crohns disease (CD) is a chronic idiopathic inflammatory disease characterized by the segmental, transmural involvement of the gastrointestinal tract. Ileocolonic and colonic/anorectal involvement is most common and account for 40% of the cases and involvement of small intestine in about 30%.1 Inflammatory Bowel Diseases (IBD), like CD, have been associated with various autoimmune conditions, with a cumulative prevalence of 8.2% to 10.5%.2 Concurrence of IBD with immune thrombocytopenia (ITP) is a rare phenomenon. Less than 20 cases have been reported in the medical literature and all of these patients had extensive colonic involvement. We are reporting a unique case, the first of its kind, of a patient with CD with isolated gastric involvement who was diagnosed with ITP. …

Synchronous metastasis of prostate adenocarcinoma to the stomach and colon: A case report

Context: Prostate cancer is the leading cancer diagnosis in males. The most common metastatic site of metastases in patients with prostate cancer is the axial skeleton and local lymph nodes. Rarely has there been a description of metastatic prostate cancer to the stomach, esophagus, small bowel, and rectum. Case Report: We report an unusual case of a patient who was diagnosed with prostate cancer with synchronous metastasis to both the stomach and sigmoid colon. A 71-year-old African American man with a history of prostate cancer was admitted with a hemoglobin level of 6.1 g/dl, which had decreased from the baseline value of 8 g/dl. He underwent an esophagogastroduodenoscopy, which revealed a nodule in the fundus of stomach; a biopsy of the nodule was done. The patient also underwent a sigmoid polypectomy. Both surgical specimens were histopathologically consistent with metastatic adenocarcinoma of prostatic origin. Conclusion: To the best of our knowledge, this is the first case report in literature of synchronous metastasis of prostate cancer to both the stomach and sigmoid colon.

An Interesting Clinical Entity of Squamous Cell Cancer of the Pancreas with Liver and Bone Metastases: a Case Report and Review of the Literature

Squamous cell pancreatic carcinoma is an exceedingly rare malignancy. The prevalence is noted at less than 1 % of the overall recorded cases of pancreatic malignancywith very few cases represented in the literature [1–3]. With such few cases, there is some debate over the exact etiology and pathogenesis of this type of cancer. The presentation and many of the clinical findings are shared with other histologic types including the much more common ductal adenocarcinoma, while others still break away from expectations. Here, we present a case of squamous cell carcinoma of the pancreas with liver and skeletal metastases as well as a discussion with a brief review of the literature.

Use of eltrombopag for the treatment of thrombocytopenia in hypoplastic myelodysplastic syndrome.

Dear Editor, Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by dysplasia in one or more of the hematopoietic cell lines, ineffective hematopoiesis resulting in peripheral cytopenias, and progressive evolution to acute leukemia [1]. The majority of patients with MDS have a normal cellular or hypercellular bone marrow, but a minority has a hypocellular marrow (defined as <30 % cellularity in patients younger than 60 years and <20 % cellularity in patients 60 years of age and older) [2]. T cell-mediated suppression of hematopoiesis is the basis for hypocellular MDS, and hence, cytopenias respond to immunosuppressive therapy. In prior clinical studies, subcutaneous romiplostim, a fusion protein analog of thrombopoeitin, has demonstrated efficacy in the treatment of thrombocytopenia in patients with lowor intermediate-1 risk MDS [3]. This is the first case report on the use of eltrombopag, a c-mpl agonist oral thrombopoietin mimetic, for the treatment of thrombocytopenia in hypoplastic myelodysplastic syndrome. An 84-year-old female with a past medical history of hypertension, dyslipidemia, and idiopathic pulmonary fibrosis was admitted to our institution for evaluation of severe epistaxis and generalized bruising. Physical examination was unremarkable except for mucosal petechial hemorrhages and generalized ecchymosis. Her laboratory studies revealed leukocyte (WBC) count of 3.6×10/L, hemoglobin (Hgb) of 9.7 g/dL, hematocrit (Hct) of 29.2 %, reticulocyte count of 0.5 %, mean corpuscular volume (MCV) of 99 fL, and platelet (Plt) count of 7×10/L. Her absolute neutrophil count was 2.5×10/L. Her coagulation parameters were normal, and the peripheral blood smear did not show any morphological abnormalities. Additionally, extensive immunologic and virology tests revealed no abnormality. Platelet transfusions were administered in an attempt to increase the platelet count with very minimal response. Bone marrow aspiration and biopsy was performed which revealed hypocellularity of <10 % associated with dysplasia consistent with a histopathologic diagnosis of hypocellular myelodysplastic syndrome with no cytogenetic aberrations. According to the World Health Organization (2008) classification, she had refractory cytopenia with multilineage dysplasia (RCMD), and her revised International Prognostic Scoring System score was 3, consistent with low risk. Flow cytometry studies for CD55 and CD59 were negative for the paroxysmal nocturnal hemoglobinuria (PNH) clone. She was started on antithymocyte antiglobulin (ATG) (40 mg/kg) plus cyclosporine (CSA) (5 mg/kg) and prednisone (1 mg/kg) for 4 days. The patient became more cytopenic and required more red blood cell and platelet transfusions as an outpatient. Three weeks later, she presented to the emergency room with severe shortness of breath, dizziness, rectal bleeding, and generalized bruising, and laboratory results revealed severe WBC count of 1.9×10/L, Hgb of 4.2 g/dL, Hct of 12.6 %, and platelet count of 12×10/L. The patient clinically responded to aggressive multiple red blood cell and platelet transfusions. During the 1-month outpatient follow-up visits, her platelet count remained consistently less than 20×10/L. She was started on eltrombopag 50 mg/day which improved her platelet count. It increased from 8×10/L at the time of initiation of the drug to 32×10/L in 1 month. Her platelet transfusion requirement was reduced over the next 4 months with platelet counts reaching above 70×10/L without transfusions. In light of the fact that we did not notice any D. Gauchan :H. Shaaban (*) :M. Maroules Department of Hematology/Oncology, St Joseph’s Regional Medical Center, Seton Hall University School of Health and Medical Sciences, Paterson, NJ, USA e-mail: hamidshaaban@gmail.com

The clinical characteristics of pulmonary embolism in patients with malignancy: A single medical institutional experience

The venous thromboembolic complication, pulmonary embolism (PE), is an important cause of death in cancer patients.[1–3] Depending on the clinical presentation, the case fatality rate for acute pulmonary embolism ranges from about 60% to less than 1%.[4] The in-hospital mortality for general medical and surgical patients with PE is up to 6% with a 30-day mortality of 9.3% and a 3-month mortality of up to 15.3%.[5]

Association between Level of Tumor Markers and Development of VTE in Patients with Pancreatic, Colorectal and Ovarian Ca: Retrospective Case- Control Study in Two Community Hospitals

The risk of venous thromboembolism (VTE) is increased in patients with cancer. However, the role of tumor markers as potential indicators of increased risk of VTE is still undetermined. In this retrospective observational case control study, levels of the tumor markers CEA, CA 19–9 and CA 125 in patients with colorectal, pancreatic, and ovarian cancer respectively, who were admitted to two community hospitals between January 2001 and December 2011, were compared between patients who were VTE positive and those who were VTE negative. The primary goal of this study was to determine whether VTE positive cancer patients had higher tumor marker levels compared to VTE negative cancer patients. In our study, 66.7% (48/72) of patients who were positive for VTE had elevated tumor markers while 65.3% (66/101) of patients who were negative for VTE had low (normal) tumor markers, indicating an association of high tumor marker levels with the diagnosis of VTE. This was statistically significant with an odds ratio of 3.77 and p-value of <0.0001 (95% CI of 1.99–7.14). When the VTE group was further divided into DVT and PE groups, 70.2% (40/57) of patients in the DVT positive group had high tumor markers with a p value of <0.0001 and an odds ratio of 3.99 (95% CI of 2.02 to 7.89) while 57.9% (11/19) of patients in pulmonary embolism positive group had high tumor markers; this was, however, not statistically significant (p-value of 0.35 and a CI of 0.59 to 4.10). In this retrospective study of 173 individuals with a diagnosis of either colorectal, pancreatic, or ovarian Cancer, higher tumor marker levels (CEA, CA 19–9, and CA 125 respectively) were associated with an increased risk of VTE, either DVT or PE. However, when further divided into either DVT or PE groups, the association remained statistically significant only for DVT but not for PE.