Rare incidence of tumor lysis syndrome in metastatic prostate cancer following treatment with docetaxel.

Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors. In this report, the authors describe a specific case of tumor lysis syndrome in a patient with metastatic prostate cancer following treatment with docetaxel.

Factors predicting use of laxatives in outpatients stabilized on clozapine.

Constipation is a common and sometimes fatal side effect of clozapine treatment. In this study, we aimed to identify factors associated with clozapine-induced constipation. Data on 202 outpatients stabilized on clozapine treatment were collected. Of these, 71 patients (35%) had a current prescription for laxatives (a proxy for the presence of constipation). Mean clozapine dose was 400.4 mg/day in those prescribed laxatives and 390.1 mg/day in those not prescribed laxatives (p = 0.67), while mean clozapine plasma concentration was 0.53 mg/l and 0.49 mg/l, respectively (p = 0.29). Patients using laxatives had on average 29% higher norclozapine concentrations (mean = 0.34 mg/l) than those who did not use laxatives (mean = 0.27 mg/l; p = 0.046). Laxative use was more common in female patients (49.1%) than male patients (29.1%; p < 0.01). Prescribers should be vigilant for constipation at any dose or plasma concentration of clozapine and should be mindful that male patients may be undertreated. Norclozapine concentrations may predict clozapine-induced constipation.

Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies.

OBJECTIVE: To systematically review published and unpublished efficacy studies of agomelatine in people with depression. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Literature search (Pubmed, Embase, Medline), Cochrane Central Register of Controlled Trials, European Medicines Agency (EMA) regulatory file for agomelatine, manufacturers of agomelatine (Servier). ELIGIBILITY CRITERIA: Double blind randomised placebo and comparator controlled trials of agomelatine in depression with standard depression rating scales. DATA SYNTHESIS: Studies were pooled by using a random effects model with DerSimonian and Laird weights for comparisons with placebo and comparator antidepressant. The primary efficacy measure (change in rating scale score) was summarised with standardised mean difference (SMD; a measure of effect size) and secondary outcome measures with relative risks. All results were presented with 95% confidence intervals. Statistical heterogeneity was explored by visual inspection of funnel plots and by the I(2) statistic. Moderators of effect were explored by meta-regression. RESULTS: We identified 20 trials with 7460 participants meeting inclusion criteria (11 in the published literature, four from the European Medicines Agency file, and five from the manufacturer). Almost all studies used the 17 item Hamilton depression rating scale (score 0-50). Agomelatine was significantly more effective than placebo with an effect size (SMD) of 0.24 (95% confidence interval 0.12 to 0.35) and relative risk of response 1.25 (1.11 to 1.4). Compared with other antidepressants, agomelatine showed equal efficacy (SMD 0.00, -0.09 to 0.10). Significant heterogeneity was uncovered in most analyses, though risk of bias was low. Published studies were more likely than unpublished studies to have results that suggested advantages for agomelatine. CONCLUSIONS: Agomelatine is an effective antidepressant with similar efficacy to standard antidepressants. Published trials generally had more favourable results than unpublished studies.

Does hormonal therapy have a therapeutic role in metastatic primary small cell neuroendocrine breast carcinoma? Case report and literature review.

Primary neuroendocrine carcinoma of breast (NECB) is a very rare tumor; the World Health Organization(WHO) subcategorized these tumors into 3 major histologic subtypes: solid, small cell carcinoma (SMCC), and large cell NE carcinoma. The SMCC subtype is the least common and most aggressive and has been reported to be as aggressive as its pulmonary counterpart. SMCC is usually confirmed based on clinical, pathologic,and imaging studies. Local disease is usually managed in a fashion similar to that of the usual ductal breast cancer; in the metastatic SMCC setting, regimens that are implemented in small cell lung cancer are usually attempted, according to case reports and published small case series. Hormone receptors can be expressed in more than 90% of the solid tumor subtype; however its expression is manifested in about 50% of cases of SMCC. Although hormonal therapy can be used successfully to treat the usual metastatic ductal breast cancer,its utility in metastatic SMCC has not been reported. We report an impressive response to hormonal therapy in a patient with late relapse of breast carcinoma with a metastatic SMCC subtype that expressed hormone receptors. The response to hormonal therapy was sustained for about 12 months. The response to hormonal therapy is definitely an interesting finding that, to our knowledge, has not been described before in the setting of metastatic SMCC. We suggest considering adding hormonal therapy to the treatment pipeline for primary SMCC of the breast that express hormone receptors.

Does Kaposi's sarcoma predict multicentric Castleman disease in the presence of generalized lymphadenopathy?

Multisystemic Castleman disease (MCD) can be associated with HHV8 infection, which involves the mantle zone of follicles. This condition results in an increase number of HHV8-positive (HHV8+) plasmablasts that multiply and amalgamate to form plasmablastic B-cell lymphoma. All previously reported cases of HIV-positive patients with MCD were coinfected with HHV8. Twelve cases of HIV- MCD that are HHV8+ were encountered in the literature, three of them developed lymphoma, and none of those cases were reported to have Kaposi's sarcoma (KS). We report a unique case of HIV-negative elderly woman with preexisting KS that presented to the hospital with recurring nausea, vomiting, and fever, assessment revealed diffuse lymphadenopathy. Axillary lymph node biopsy showed HHV8+ MCD with foci of microlymphoma. Despite the treatment with high-dose steroids, she developed multisystem failure that lead to her death.

Severe refractory autoimmune hemolytic anemia with both warm and cold autoantibodies that responded completely to a single cycle of rituximab: a case report.

INTRODUCTION: Mixed warm and cold autoimmune hemolytic anemia runs a chronic course with severe intermittent exacerbations. Therapeutic options for the treatment of hemolysis associated with autoimmune hemolytic anemia are limited. There have been only two reported cases of the effective use of rituximab in the treatment of patients with mixed autoimmune hemolytic anemia. We report a case of severe mixed autoimmune hemolytic anemia that did not respond to steroids and responded to four weekly doses of rituximab (one cycle). CASE PRESENTATION: A 62-year-old Caucasian man presented with dyspnea, jaundice and splenomegaly. His blood work revealed severe anemia (hemoglobin, 4.9 g/dL) with biochemical evidence of hemolysis. Exposure to cold led to worsening of the patient's hemolysis and hemoglobinuria. A direct antiglobulin test was positive for immunoglobulin G and complement C3d, and cold agglutinins of immunoglobulin M type were detected. A bone marrow biopsy revealed erythroid hyperplasia. A positron emission tomographic scan showed no sites of pathologic uptake. There was no other evidence of a lymphoid or myeloid disorder. Initial therapy consisted of avoidance of cold, intravenous methylprednisolone and a trial of plasmapheresis. However, there was no clinically significant response, and the patient continued to be transfusion-dependent. He was then started on 375 mg/m2/week intravenous rituximab therapy. After two treatments, his hemoglobin stabilized and the transfusion requirement diminished. Rituximab was continued for a total of four weeks and led to the complete resolution of his hemolytic anemia and associated symptoms. At the patient's last visit, about two years after the initial rituximab treatment, he continued to be in complete remission. CONCLUSION: To the best of our knowledge, this is the first reported case of mixed-type autoimmune hemolytic anemia that did not respond to steroid therapy but responded completely to only one cycle of rituximab. The previous two reports of rituximab use in mixed autoimmune hemolytic anemia described an initial brief response to steroids and the use of rituximab at the time of relapse. In both of these case reports, the response to one cycle of rituximab was short-lived and a second cycle of rituximab was required. Our case report demonstrates that severe hemolysis associated with mixed autoimmune hemolytic anemia can be unresponsive to steroid therapy and that a single cycle of rituximab may lead to prompt and durable complete remission.

Secretion of beta-human chorionic gonadotropin by non-small cell lung cancer: a case report.

INTRODUCTION: We describe a case of non-small cell lung cancer that was found to stain positive for beta-human chorionic gonadotropin on immunohistochemistry. Only a few case reports have described lung cancers that secrete beta-human chorionic gonadotropin. CASE PRESENTATION: A 68-year-old Caucasian man presented with symptoms of weakness, fatigue and weight loss for the past two months. On examination, he was found to have generalized lymphadenopathy, and radiologic workup revealed numerous metastases in the lungs, liver and kidneys. Biopsy of the supraclavicular lymph node revealed metastatic large cell lung cancer with beta-human chorionic gonadotropin hormone positivity. The serum beta-human chorionic gonadotropin level was 11,286 mIU/ml (upper limit of normal, 0.5 mIU/ml in non-pregnant females). He was diagnosed with stage 4 lung non-small cell lung cancer. The patient refused chemotherapy. He was discharged home with hospice care. CONCLUSION: The markedly elevated serum values of beta-human chorionic gonadotropin initially prompted the medical team to investigate germinal tumors. In the presence of a negative testicular ultrasound, workup was performed to find an extratesticular source of the tumor. Finally, the diagnosis was made with a tissue biopsy. This case illustrates that atypical markers can be seen in many cancers, emphasizing the role of immunohistochemistry and tissue biopsy in establishing the diagnosis.

Renal epithelioid angiomyolipoma: a malignant disease.

BACKGROUND: Renal angiomyolipomas are recognized as clonal neoplasms with clonal chromosomal aberrations and a common progenitor cell, the perivascular epithelial cell (PEC). The epithelioid variant is a recently identified entity, characterized by predominance of PEC and a unique morphologic and immunohistochemical profile. There is accumulating evidence suggesting that renal epithelioid angiomyolipoma (REA) is a malignant disease. METHODS: We searched the literature for descriptions of clinical behavior of REA. A Pubmed search was performed using the following key words: angiomyolipoma, epithelioid, perivascular epithelial cell or/and renal tumors. We reviewed a case of fatal REA at our institution. A pathologist reviewed slides to confirm the diagnosis. RESULTS: Upon review of 140 articles, 37 eligible articles were found including 10 articles describing the clinical course of REA. Almost all of the patients described, for whom there was a follow-up available, died of neoplastic progression of the disease, with liver, lung and bone metastases. Four cases were reclassified after retrospective pathology review, and they were fatal. Three of these had been misdiagnosed as renal cell carcinoma (RCC), while 1 was diagnosed as classic angiomyolipoma. CONCLUSION: Unlike commonly benign classic angiomyolipoma, REA behaves aggressively. It is crucial for the clinician to be aware of and identify this epithelioid variant as a malignant disease. It should be carefully differentiated from RCC. Resection alone may not be curative, and adjuvant therapy should be considered. A multimodality treatment approach needs to be explored for this newly recognized malignant variant renal angiomyolipoma.

Unilateral orbital pain and eyelid swelling in a 46-year-old woman: orbital metastasis of occult invasive lobular carcinoma of breast masquerading orbital pseudotumour.

Orbital metastasis is very infrequent in breast cancer; more so as an initial and sole presenting feature. The authors report a case of orbital metastasis of occult breast carcinoma in a 46-year-old woman, who presented with unilateral orbital pain and eyelid swelling. This was initially diagnosed as orbital pseudotumour and treated with steroids. The development of breast symptoms and finding of breast nodule, 3 months later, led to the diagnosis of invasive lobular carcinoma of the breast with orbital metastases, confirmed on biopsy.

Recurrent imatinib-induced hepatotoxicity in a chronic myeloid leukaemia patient successfully managed with prednisone.

Imatinib, the frontline tyrosine kinase inhibitor (TKI), has revolutionised the management of chronic myeloid leukaemia (CML). Severe hepatotoxicity, although uncommon, can occur with this drug. This tends to subside with dose reduction or cessation, but can recur with reintroduction of the drug. Recurrent severe hepatotoxicity mandates permanent discontinuation of imatinib. This can cause difficulties in the management of CML, more so if the patient cannot afford or get access to alternate therapy. Furthermore, alternate therapy, for example, second-line TKIs, can impose a huge economic burden on a healthcare system. Here, the authors report the case of 20-year-old CML patient who developed recurrent hepatotoxicity with the use of imatinib. Introduction of corticosteroids enabled successful reintroduction of imatinib therapy.

Clozapine-related EEG changes and seizures: dose and plasma-level relationships.

Clozapine is a widely used atypical antipsychotic with a unique effectiveness in treatment-resistant schizophrenia. An important adverse effect is seizures, which have been observed at all stages of clozapine treatment. Valproate has traditionally been considered the drug of choice for the prophylaxis of clozapine seizures, however it may not be the most suitable choice for all patients. There is disagreement as to the best point to prescribe valproate or a suitable antiepileptic: as seizure prophylaxis at a certain clozapine dose or level, or only as remedial treatment. In this review, we examine the relevant literature with an aim to evaluate the following relationships: clozapine dose and electroencephalogram (EEG) abnormalities, plasma levels and EEG abnormalities, dose and occurrence of seizures and plasma levels and occurrence of seizures. Weighted linear regression models were fitted to investigate these relationships. There was a strong relationship between clozapine dose and plasma level and occurrence of clozapine-induced EEG abnormalities. However, a statistically significant relationship between dose and occurrence of seizures was not found. A relationship between clozapine plasma level and occurrence of seizures was not established because of the scarcity of useful data although our review found three case reports which suggested that there is a very substantial risk of seizures with clozapine plasma levels exceeding 1300 µg/l. Seizures are more common during the initiation phase of clozapine treatment, suggesting a slow titration to target plasma levels is desirable. An antiepileptic drug should be considered when the clozapine plasma level exceeds 500 µg/l, if the EEG shows clear epileptiform discharges, if seizures, myoclonic jerks or speech difficulties occur and when there is concurrent use of epileptogenic medication. The antiepileptics of choice for the treatment and prophylaxis of clozapine-induced seizures are valproate (particularly where there is mood disturbance) and lamotrigine (where there is resistance to clozapine).

Need for parenteral iron therapy after bariatric surgery.

BACKGROUND: Malabsorptive bariatric procedures such as Roux-en-Y gastric bypass and biliopancreatic diversion/duodenal switch expose the patient to malnutrition and commonly cause iron deficiency. The optimal replacement and monitoring method remain undetermined. To identify high-risk patients who might need intravenous iron supplementation after bariatric surgery, we evaluated bariatric surgery patients who received parenteral iron at a university hospital-affiliated hematology center. METHODS: We performed a retrospective analysis and reviewed the records of 165 patients who had received parenteral iron from May 2004 to June 2007. Of the 165 patients, 42 bariatric surgery patients were identified. The type of bariatric procedure and menstrual status of the patients were compared. RESULTS: The average patient age was 40 years. Of the 42 patients, 2 were men and 40 were women. Of the 40 women, 32 were premenopausal and 8 were postmenopausal. The patients in the biliopancreatic diversion/duodenal switch group had a significantly lower hemoglobin at presentation (P = .02), relatively lower ferritin levels, and required more additional parenteral iron treatment after the initial resolution of anemia (P = .001). The premenopausal women required earlier parenteral replacement (P = .008) and were at a greater risk of anemia-related hospitalization (P = .00033). CONCLUSION: The available published studies lack any data regarding parenteral iron replacement needs after bariatric surgery. Our results have identified the need for long-term parenteral iron replacement therapy after malabsorptive bariatric procedures, especially in premenopausal women. Patients who do not respond to oral iron therapy should be referred early for parenteral iron replacement therapy to prevent anemia-related complications and to maintain patients' quality of life. Iron monitoring should continue indefinitely even after the initial repletion of iron stores and the resolution of anemia.

Bilateral hilar lymphadenopathy in a young female: a case report.

Hilar or mediastinal lymphadenopathy is not included in the wide spectrum of radiologic findings associated with bronchiolitis obliterans-organizing pneumonia (BOOP). We present a patient who presented with extensive hilar and mediastinal lymphadenopathy. We suspected a diagnosis of sarcoidosis. The patient was diagnosed with idiopathic BOOP. This is the first case demonstrating that BOOP, now referred to as cryptogenic organizing pneumonia (COP), can present with bilateral hilar lymphadenopathy.

Increased breast calcifications in women with ESRD on dialysis: implications for breast cancer screening.

BACKGROUND: Different appearances of breast calcification on mammography can differentiate benign from malignant disease. An increased incidence of breast calcifications in dialysis patients is established, but data for morphological characteristics in renal patients, incidence of benign and malignant calcifications, and clinical consequences are limited. In this study, we compare mammograms and the workup of abnormal calcifications of women on hemodialysis with that of women with normal renal function. METHODS: This is a retrospective case-control study; 45 women on hemodialysis had their screening mammograms reviewed. A control group of 86 age-matched women with normal renal function was randomly obtained for comparison. Mammograms were examined and the recommended workup was traced. Breast calcification morphological characteristics, incidence of benign versus malignant calcifications, callback rate, and biopsy recommendation rates were compared to determine whether breast calcifications in renal patients led to excessive workups. RESULTS: Overall, breast calcifications in the renal group were statistically significantly increased compared with controls, mostly because of several benign-appearing morphological characteristics. No statistically significant difference was present between the 2 groups with respect to callback rates. However, incidences of malignancy-associated calcification and hence biopsy recommendation rate were slightly greater for the renal group. CONCLUSION: Renal patients have an increase in breast calcification, mostly caused by several benign calcifications. The callback rate is no greater than that in the general population. However, there is a slightly greater incidence of malignancy-associated calcifications; hence, once called back, they have a greater probability of being recommended for biopsy.