Gunwant Guron

A case of DRESS (drug reaction with eosinophilia and systemic symptoms) with acute interstitial nephritis secondary to lenalidomide

Acute kidney injury is commonly observed in patients with multiple myeloma and other plasma cell dyscrasias. The pathophysiologic causes, however, are varied. We report a case of a severe ‘drug reaction with eosinophilia and systemic symptoms’ syndrome associated with acute interstitial nephritis in a patient with multiple myeloma likely related to the administration of lenalidomide. This disease entity requires prompt recognition and cessation of the offending drug and often treatment with high-dose corticosteroids.

Is there an association between human immunodeficiency virus infection and breast cancer

Sir, Breast carcinoma is the second most common cause of female cancer deaths in the United States of America [1]. There has been no demonstrated association between HIV infection and breast cancer. The acquired immunodeficiency syndrome (AIDS) defining neoplasms are Kaposi’s sarcoma, non-Hodgkin lymphoma, and cervical cancer [2]. There are malignancies that are more prevalent in AIDS patients than general population. They are called non-AIDS defining cancers (NADCs) such as Hodgkin’s lymphoma, squamous cell carcinoma of anus, liver cancer, head and neck and lung cancer [3]. The data about breast cancer incidence and prognosis in HIV patients are limited and conflicting although most recently, it has been stipulated that breast cancer is more aggressive in the HIV-infected patient. To explore the relationship of HIV infection and breast cancer, we have reviewed our experience at St Michael’s Medical Center (SMMC) where over 1,000 patients are treated annually for HIV infection. We reviewed the data of 12 HIV patients in the tumor registry records who were diagnosed with breast cancer between January 1997 and December 2007 with attention to sex, age, race/ethnicity, HIV variables including CD4 count and viral load, disease stage at presentation, tumor characteristics, and patient survival. The twelve HIV-infected patients with breast cancer had a mean age of 54 ranging from 47 to 70. There was only one man. Breast carcinoma was diagnosed from 8 months to 8 years after the patient was tested positive for HIV, with a median of two and a half years. The mode of HIV transmission was mainly unprotected sex. The median CD4 count was 410.25% were diagnosed at stage I, 50% were staged at 2/3 and 25% at stage IV. Three tumors were triple negative. The median BMI was 24.9.33% of the patients underwent chemotherapy with poor tolerance. About 33% of HIV-infected breast cancer patients had negative survival outcomes and 100% of them were secondary to breast cancer complications. And 50% of the breast cancer survivors have lived for more than 5 years after being treated with surgery and tamoxifen. Most patients reported had a CD4 count, which was above the threshold considered critical for significant immunosuppression suggesting that, the degree of immunocompromise (i.e., CD4 count) is not correlated with tumorigenicity. Our results demonstrate that the decision of chemotherapy should be a cautious one with HIV-infected breast cancer patients with poorly differentiated, aggressive disease because of potential fatal complications. Whether this factor is related to a more aggressive breast cancer associated with HIV in addition to the inability to administer full systemic chemotherapy doses is a subject that needs to be studied further [4]. HIV can augment the immunosuppression induced by chemotherapy but it is also possible that chemotherapy can accelerate the progression of HIV disease. It still remains unclear if breast carcinoma can be directly linked to HIV infection.

The clinical efficacy of using autologous platelet rich plasma in hip arthroplasty: A retrospective comparative study

Background: Platelet rich plasma (PRP) is a blood derivative concentrate of platelets, fibrin and growth factors obtained through withdrawal and centrifugation of autologous blood and use for its inherent hemostatic and adhesive properties to promote wound healing. Hip arthroplasty is often associated with significant perioperative complications including blood loss necessitating blood transfusions, which can lead to multiple adverse reactions, infection transmission, and longer hospital stay. Materials and Methods: We conducted this retrospective comparative study to determine whether the use of PRP can reduce the bleeding complications in hip replacement surgeries and therefore decrease analgesic requirements and shorten the hospital stay. Results: Sixty patients had consecutive hip replacement surgeries. The study group (n=23) received PRP applications while the control group (n=37) were operated without PRP applications. Postoperative drop of hemoglobin, number of red blood cell (RBC) transfusions, analgesic requirements, and duration of hospital stay were recorded. There was no significant difference in the drop of hemoglobin preoperatively and postoperatively comparing study and control groups (P=0.75). There was no difference in transfusion requirements between the two groups (P=0.16) but there was trend toward less transfusion in the PRP-treated group. There were also no statistical differences in analgesic use (P=0.83) and lengths of hospitalization (P=0.68) between the two groups. Conclusion: We concluded that there is no clinical efficacy in using PRP in hip replacement surgeries. We recommend a larger prospective study be conducted to determine its clinical utility as an optimization strategy to improve outcome after hip arthroplasty

Citrobacter freundii-induced cold agglutinin hemolysis

Dear Editor, A 64-year-old Hispanic woman with a past medical history of hypertension, diabetes mellitus type 2, and dyslipidemia was admitted with symptoms of fever, left-sided flank pain, and blood in her urine of 2 days duration. Seven days before admission, the patient had been treated as outpatient for urinary tract infection with trimethoprim/sulfametoxazole (Bactrim). Physical exam revealed left costovertebral angle tenderness and some scleral icterus. The patient was awake, alert and oriented, and showed no changes in mental status. Her temperature was febrile, 38.5°C. Initial laboratory results revealed a hemoglobin (Hgb) of 8.2 g/dL, hematocrit of 23.6 g/dL, platelet count of 524,000×10/μL, creatinine of 1.1 mg/dL, a total bilirubin of 1.6 mg/dL, haptoglobin of 5.8 mg/dL, and a lactic dehydrogenase of 699 U/L. Blood cultures returned positive for Citrobacter freundii within 24 h of collection. A direct Coombs’ test (DAT) was positive for C3d but negative for IgG, and high-titer cold agglutinins were detected. Tests for influenza A and B, Epstein–Barr virus, and Mycoplasma were negative. The patient was treated for Citrobacter infection and transfused with warm blood. She was kept in a heated room with body warming blankets. Two days after admission, the patient’s Hgb dropped to 5.4 g/dL, with increasing lactic dehydrogenase levels and indirect bilirubin suggesting an ongoing active hemolysis. The patient was started on intravenous methylprednisolone 80 mg IV daily for 10 days, and the hemolysis resolved. Her Hgb improved gradually to 7.8 g/dL, and repeat blood cultures as well as a repeat DAT were negative. Subsequently, she was discharged home on a tapering dose of oral corticosteroids. Four weeks after discharge, corticosteroids were completely stopped without any relapse of cold agglutinins. Several viral and bacterial pathogens have been reported in the literature as causative factors for secondary cold agglutinin disease. Cytomegalovirus, parvovirus B19, and varicella-zoster virus are commonly associated viral etiologies. Mycoplasma pneumoniae, Chlamydia, Legionella, and Leptospira have been reported as bacterial predisposing agents to cold agglutinin disease as well [1, 2]. To our knowledge, ours is the first case of Citrobacterassociated cold agglutinin hemolysis to be reported in the literature. Citrobacter bacteria are gram-negative rods belonging to the Enterobacteriaceae family and are often found in water supplies as well as food sources, in addition to other parts of the environment [3]. In some humans, Citrobacter is part of the normal bacterial flora of the colon, but this occurs in only a small percentage of the population. In our patient, the concomitant sepsis with C. freundii is the likely precipitating factor for the cold agglutinininduced hemolytic anemia. The spontaneous resolution of cold agglutinins as well as hemolysis after the treatment of Citrobacter sepsis supports Citrobacter as the most likely trigger [4]. C. freundii has been reported in the past as one of the causes of Shiga toxin-mediated hemolytic uremic syndrome [5]; however, cold agglutinin disease has never been associated with it. Like in cases associated with Mycoplasma pneumoniae, it is possible that some polyclonal IgM cold agglutinins arise in association with Citrobacter A. Kumar (*) Department of Medicine, Saint Michael’s Medical Center, 111 Central Avenue, Newark, NJ 07101, USA e-mail: Ice9996@aol.com

The role of red cell distribution width as a predictor of mortality for critically ill patients in an inner-city hospital

Background: Red cell distribution width (RDW) is a measure of the variation in the red blood cell volume that is usually recorded as a part of the standard complete blood cell count. Recent studies have demonstrated the prognostic value of RDW in many different clinical settings. The objective of this research study is to investigate the independent association of RDW with 30-day mortality in Intensive Care Unit (ICU) patients. Methods: One hundred and fifty-six patients admitted to the ICU of our hospital between July 2009 and June 2011 were included in our study. Out of 156 patients, 124 survived the hospital stay. The data on patients demographics, interventions done in ICU, and their comorbidities were collected. Baseline variables and the RDW value were compared between survivors and nonsurvivors. The cutoff point for RDW used for the comparison was 15.75. Both univariable and multivariable analyses were done. P < 0.05 was considered statistically significant. Results: In the univariable analysis of the study between survivors and nonsurvivors, the median RDW was 17.20 for nonsurvivors, implying statistical significance (P = 0.007). In multivariable analysis, RDW remained significantly associated with inpatient mortality. The receiver operating characteristic is 0.656 (P = 0.007), with an optimal cutoff of 15.75 for RDW. At the cutoff of RDW, i.e., 15.75, the sensitivity and specificity for inpatient mortality was 71% and 89%, respectively. Conclusion: In critically ill ICU patients, RDW is an independent predictor of 30-day mortality. Taking into consideration the fact that RDW is routinely measured in complete blood count with no additional cost, this can serve as an “inexpensive prognostic marker” in critically ill patients.

Nodular sclerosing Hodgkin's lymphoma with breast involvement: Case report and review of the literature.

Extranodal disease in Hodgkins lymphoma (HL) is very rare and it occurs in 15-30% of all cases. The intrathoracic area is the most common extranodal presentation. There are very few cases in the medical literature of breast involvement with HL. We report a 25-year-old woman who had been managed and treated for nodular sclerosing HL for 6 months, but she was noncompliant with chemotherapy. She presented 1 year later with a palpable left breast mass and B symptoms. The fluorine-18 fluorodeoxyglucose-positron emission tomography images revealed disseminated disease with a left breast mass demonstrating fluorodeoxyglucose uptake. Histopathology of the ultrasound-guided biopsy specimen of the breast mass was consistent with recurrence. This case highlights the need for an awareness of HL presenting in this way because the diagnosis has therapeutic and prognostic implications.

Diffuse gastroduodenal metastasis from cutaneous malignant melanoma presenting as amelanotic "volcano-like" ulcers.

To the Editor, Malignant melanoma is primarily a dermatological malignancy, and it has been reported to metastasize to all organs of the human body. Metastases to the gastrointestinal (GI) tract are rarely diagnosed before death. With the increasing utilization of radiological and endoscopic techniques, metastases to the GI tract can present both at the time of primary diagnosis or several years later as the first sign of recurrence. The small bowel is the most common intestinal site for metastases. There is little in the medical literature with regards to gastroduodenal metastases, and the data are limited to a few case reports [1]. Symptoms typically include abdominal pain, fatigue, dysphagia, constipation, tenesmus, small bowel obstruction, perforated bowel, hematemesis, and melena [2]. A 58-year-old African-American male with a past medical history of schizophrenia, depression, and arthritis was initially evaluated for a lesion on his left buttock which was itchy and was bleeding upon scratching. Excisional biopsy demonstrated an anaplastic malignant melanoma with Breslow thickness of 9 mm. Subsequently, the patient underwent a wide excision of the lesion from the left buttock with 2-cm surgical margins along with left inguinal sentinel node mapping and biopsy. The patient was also found to have a 3-mm satellite nodule of malignant melanoma in the subcutaneous adipose tissue located 9 mm from deep and superior margin. Computed tomography of the head, chest, and abdomen was negative for metastases. Themelanomawas staged as T4pN0M0 (stage 2C). The patient received radiotherapy for 6 weeks. Eight months later, he started complaining of melena, and upper endoscopy studies revealed amelanotic polypoid masses with ulcerations at the tip, “volcano-like” ulcers, in the antrum of the stomach (Fig. 1a) and duodenum (Fig. 1b). Histomorphology of the gastric fundal fine endoscopic punch biopsy showed extensive loss of the parietal cells and replacement by antral type glands and pancreatic acinar-like cells along with heavy lamina propria inflammation and goblet cell metaplasia of the surface lining epithelium. Tumor cells are also seen infiltrating the lamina propria (H&E, ×250) (Fig. 2). Immunohistochemical staining of duodenal ulcer biopsy was positive for melan A, HMB-45, and S-100 consistent with a metastatic malignant melanoma. A week later, the patient complained of blurry vision and dizziness. The magnetic resonance imaging of his brain revealed multiple enhancing lesions in the right frontal lobe, parietal lobe, and right cerebellum consistent with metastasis. He received palliative whole-brain radiation therapy. BRAF V600E mutation analysis was negative, and hence, the patient was not a candidate for BRAF inhibitor therapy. He refused further management and chose to transfer to a different institution to enroll in a clinical trial. Distinguishing between a primary GI mucosal melanoma and a melanoma metastatic to the GI tract from a regressed or treated cutaneous primary may be difficult. Primary GI melanomas are rarely diagnosed at an early stage, are typically more aggressive, and are associated with a worse prognosis [3]. The most common subtype of melanoma that metastasizes to the GI tract is superficial spreading melanoma [4]. On endoscopic studies, they present as multiple ulcerated polypoid lesions and may be either pigmented or amelanotic [5]. Treatment of metastatic melanoma to the GI tract may H. Shaaban (*) :G. Guron Hematology and Oncology Department, St Michael’s Medical Center, 111 Central Avenue, Newark, NJ 07102, USA e-mail: hamidshaaban@gmail.com

A rare case of non-immune hemolytic anemia in a patient with metastatic breast cancer treated with capecitabine

Fluoropyrimidine compounds, with 5-fluorouracil (5-FU) as their principal representative, have been the mainstay of chemotherapy for solid tumors for over 40 years. 5-FU, either as monotherapy or in combination with other cytotoxic agents, is used in many standard treatment regimens for common solid tumors, including breast and colorectal cancers [1, 2]. A 70-year-old African American female had presented to us with altered mental status. She had a past medical history of metastatic breast cancer (triple hormone receptor negative) diagnosed 2 years prior to admission and had been treated with docetaxel and carboplatin. She was currently not taking any medications. As part of diagnostics, she subsequently had a CT Scan of the head that revealed frontal lobe metastases. After completion of palliative whole brain radiation therapy, she was started on palliative chemotherapy with oral capecitabine 500 mg four times a day. Four days later, she came to the emergency room complaining of progressive worsening of weakness, fatigue, and exertional dyspnea. On physical exam, she had bilateral icteric sclerae. Otherwise, rest of physical exam was unremarkable. Blood examinations showed normal renal function (creatinine 1.09 mg/dl), anemia (Hb 6.6 g/dl), platelet count 182,000, glucose 110 mg/dl, AST 88 U/l, ALT 30 U/l, bilirubin total 3.0 mg/dl, bilirubin indirect 2.1 mg/dl, and albumin 2.5 g/dl. The coagulation parameters were also within normal limits. Table 1 reveals the laboratory data. The diagnosis of hemolytic anemia was made (Hb 6.6 g/dl, haptoglobin 5.8 mg/dl, reticulocytes 6.0 %, LDH 385 U/l). She was prescribed two units of packed red blood cells (RBC). The capecitabine was held, and hemolytic parameters were monitored. Five days later, there was clinical resolution of the hemolytic anemia. After improvement in the clinical condition, the patient was discharged with no evidence of hemolytic anemia recurrence. We noted that the temporal relationship between capecitabine use and the appearance of the hemolytic anemia, and the rapid recovery and lack of relapse after drug cessation, was suggestive of a causal relationship. There are reports of hemolytic anemia being associated with administration of a number of other cytotoxic agents including oxaliplatin, carboplatin, cisplatin, methotrexate, melphalan, and doxorubicin [3]. Physicians should always consider the possibility of drug-induced hemolytic anemia in any patient who has a sudden or unexplained drop in hemoglobin concentration while undergoing chemotherapy. The observed alterations in hemolytic parameters suggest that fluoropyrimidines may exert a class effect that is fully reversible after cessation of therapy. 5-FU-mediated inhibition of thymidylate synthetase in erythroid cells (leading to inhibition of DNA synthesis) causes an increase in Mean Corpuscular Volume, and we hypothesize that hemolysis may occur because of defective formation of the red cell membrane that results from fluoropyrimidine-mediated H. Shaaban (&) St Michael’s Medical Center, 111 Central Avenue, Newark, NJ, USA e-mail: hamidshaaban@gmail.com

A rare case report of 8p11 myeloid and lymphoid neoplasm with FGFR1 abnormality in a young adult

Dear Editor, The 8p11 myeloproliferative syndrome is now classified by the World Health Organization as myeloid and lymphoid neoplasm with fibroblast growth factor receptor 1 (FGFR1) abnormality. It is a rare hematologic malignancy that involves the fibroblast growth factor receptor 1 gene at chromosome 8p11 [1]. Hematologic neoplasms with FGFR1 rearrangement are thought to derive from a pluripotent hematopoietic stem cell. They have heterogeneous clinical presentations including a myeloproliferative neoplasm or, in transformation, as acute myelogenous leukemia, Tor B-lineage lymphoblastic lymphoma/leukemia, or mixed phenotype acute leukemia [2]. A 25-year-old man was presented with rapidly enlarging cervical lymphadenopathy and low-grade fever (38 °C) of 6week duration. His medical history was unremarkable. On examination, there was a 7-cm block of bilateral cervical lymph nodes, 5-cm bilateral axillary lymph nodes, and 5-cm bilateral inguinal lymph nodes. He also had palpable hepatosplenomegaly. The remainder of physical examination was normal. Initial investigations showed a leukocyte count of 98,400/L (neutrophils 60 %, lymphocytes 13 %, monocytes 12 %, eosinophils 9 %, and myelocytes 6 %), hematocrit 53.5 %, hemoglobin 18.1 g/dL, platelets 134,000/L, LDH 599 U/L (normal, <220 U/L), and uric acid 8.1 mg/dL (normal, 1.5 mg/dL). Liver and renal function tests were normal. Chest and abdomen CT scanning revealed cervical, axillary, mediastinal, retroperitoneal, and inguinal lymphadenopathies and mild hepatomegaly. There was also splenomegaly, measuring up to 19 cm at its longest dimension. Needle aspiration of the cervical mass revealed hypercellular aspirate smears comprised of lymphoblasts, smaller lymphoid cells, and eosinophils; occasional lymphoblasts assumed hand-mirror configuration. Lymph node biopsy revealed a pararcortical pattern of infiltration by small-/medium-sized lymphoblasts admixed with eosinophils. Flow cytometry analysis of the malignant cells demonstrated CD2, CD5, CD7, terminal deoxyribonucleotidyl transferase positivity with co-expression of CD4, and CD8, confirming the diagnosis of T-lymphoblastic lymphoma (TLBL). There was striking hypercellularity because of granulocytic proliferation with prominent eosinophils (Fig. 1). The concomitant clinical presentation of T-LBL with eosinophilia and myeloproliferative disease led to the initiation of a diagnostic workup to investigate for 8p11 myeloproliferative syndrome. The bone marrow aspirates revealed myeloproliferation and increased number of myeloblasts. Bone marrow cytogenetics demonstrated the translocation t(8;13)(p11;q12)

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]