Ziad Salem

Ocular toxicity in low-dose tamoxifen: a prospective study

Purpose To look at the incidence, symptomatology, course and reversibility of low-dose tamoxifen ocular toxicity.Methods Sixty-five women with breast cancer, on tamoxifen oral therapy (20 mg/day), and a totally normal eye examination, were prospectively followed up. A full ophthalmic evaluation was done every 6 months, for a median of 30 months (range 4-79 months). Any sign of toxicity in the cornea, lens, retina or optic nerve was looked for, whether associated with a change in visual acuity or not.Results Ocular toxicity was documented in 8 patients, giving an incidence of 12%. Seven patients had keratopathy in the form of subepithelial deposits, whorls and linear opacities. Three of these patients had a concurrent symptomatic bilateral pigmentary retinopathy that warranted discontinuation of therapy. One patient developed bilateral optic neuritis that left her with optic nerve pallor and a decrease in vision. The patients who had the toxicity had a significantly higher tamoxifen cumulative dose (p = 0.03), and were longer on treatment (p = 0.04), than the non-affected ones. The keratopathy changes were reversible upon discontinuation of the drug.Conclusion Prompt reporting of symptoms and yearly ophthalmic examinations are mandatory in patients on tamoxifen to detect toxic effects while these are still reversible.

Loss of CD20 expression in relapsed lymphomas after rituximab therapy

Abstract: The response rate at relapse to rituximab in prior responders B‐cell non‐Hodgkins lymphoma (NHL) patients is below 50%. Loss of CD20 expression after rituximab therapy may explain this secondary resistance. However, the frequency of CD20 negative relapses cannot be assessed since most patients that relapsed after rituximab therapy have not been re‐biopsied. Here, we present two patients with CD20 positive low grade B‐cell NHL that lost the cell surface and cytoplasmic expression at relapse after rituximab therapy. Our findings suggest that confirmation of CD20 expression on the malignant B cells is required whenever rituximab therapy is considered.

Thiamine-responsive myelodysplasia

The triad of thiamine‐responsive anaemia, diabetes mellitus and deafness has been reported in 15 patients with macrocytic anaemia, sometimes associated with moderate thrombocytopenia. The bone marrow aspirate usually shows megaloblastic changes and ringed sideroblasts. However, tri‐lineage myelodysplasia has never been reported. We describe two patients who presented with diabetes, deafness and thiamine‐responsive pancytopenia. Bone marrow aspirate and biopsy were typical of tri‐lineage myelodysplasia. These findings suggest that thiamine may have a role in the regulation of haemopoiesis at the stem cell level. We propose the term ‘thiamine‐responsive myelodysplasia’ rather than that of thiamine‐responsive anaemia.

Ocular Findings in Aplastic Anemia

Objective: To analyze the ocular findings in aplastic anemia. Design: Eighteen patients with aplastic anemia were examined. Results: Ocular findings included cotton wool spots (38%), nerve fiber layer or preretinal hemorrhages (67%), vitreous hemorrhages (13%), a picture resembling central retinal vein occlusion (13%) and optic disk edema (6%). Preretinal hemorrhages were the presenting sign of aplastic anemia in 2 patients (13%). Conclusions: A blood profile is needed in patients with unexplained retinal hemorrhages. Patients with aplastic anemia need to avoid ocular massage and Valsalva maneuvers to decrease ocular morbidity.

Ratio Between Positive Lymph Nodes and Total Excised Axillary Lymph Nodes as an Independent Prognostic Factor for Overall Survival in Patients with Nonmetastatic Lymph Node-Positive Breast Cancer

Background.The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis.Methods.We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<.25, .25–.49, .50–.74, .75–1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS.Results.On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ≥.25.Conclusions.Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Autoerythrocyte sensitization (Gardner-Diamond) syndrome.

Abstract: We describe the clinical presentation and course of a patient with autoerythrocyte sensitization (Gardner–Diamond) syndrome, and review the literature for similar cases. A 37‐yr‐old female presented with recurrent episodes of painful ecchymotic bruising over the anterior aspect of both thighs. These episodes were precipitated by emotional stress. The diagnosis was confirmed by induction of similar lesions by intradermal injection of the patients own washed red blood cells and hemoglobin. The lesions did not recur for 6 months after the cause of her emotional stress was relieved. Autoerythrocyte sensitization (Gardner–Diamond) syndrome should be considered in the differential diagnosis of purpura, especially in patients with psychiatric problems.

Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor

This is the first report of granulocyte macrophage-colony stimulating factor (GM-CSF) inducing accelerated healing of a sacral pressure ulcer in a bedridden patient with bilateral hemiplegia. GM-CSF was diluted and injected locally around and into the ulcer bed every 2-3 days for 2 weeks, then weekly for 4 weeks until complete healing occurred. A new firm granulation tissue was noted within a few days. The ulcer showed 85% healing within 2 weeks and 100% by 2 months. Healing started from the periphery and from within the ulcer bed at sites of GM-CSF injections. It was slower at areas where there was complete necrosis and detachment of skin from underlying tissue. The ulcer remained closed until the patients sudden death 9 months later. A biopsy of granulation tissue showed inflammatory cells and reactive fibroblasts. The potential role of GM-CSF and growth factors in pressure ulcer therapy and wound healing are discussed.

JAK2 V617F Gene Mutation in the Laboratory Work-Up of Myeloproliferative Disorders: Experience of a Major Referral Center in Lebanon

AIMS JAK2 V617F mutation is gaining more acceptance in laboratory testing as part of the differential diagnosis work-up of myeloproliferative disorders (MPD). This report is the first of its kind from Lebanon that analyzes the distribution of this mutation among a series of referred cases to a major tertiary referral center. METHODS Real-time polymerase chain reaction using JAK2 V617F MutaScreen assay (IPSOGEN Cancer Profiler) was performed on 229 patients. RESULTS JAK2 V617F mutation was found to be positive in 100% of polycythemia vera cases, 68.29% of essential thrombocythemia cases, and 55.28% of all MPD cases whereas negative in idiopathic erythrocytosis, reactive thrombocytosis, and other non-MPD cases such as acute chronic myeloid leukemias. CONCLUSION Our unique study in this sample of Lebanese patients shows extensive similarities of positivity of JAK2 V617F as compared with the international literature and for the same categories of clinical entities. This will constitute a baseline for future clinical studies that would also help determine prognosis of cases based on the absence or presence of this mutation.

Plasmapheresis in asparaginase-induced hypertriglyceridemia

BACKGROUND: Asparaginase is an essential component of the chemotherapy regimens during the induction and intensification phases for acute lymphoblastic leukemia and lymphoblastic lymphoma. The administration of asparaginase can cause elevation of the triglyceride levels.

Genetic polymorphisms of CYP2E1, GST, and NAT2 enzymes are not associated with risk of breast cancer in a sample of Lebanese women.

Changes in the activity of drug metabolizing enzymes (DMEs) are potentially associated with cancer risk. This relationship is attributed to their involvement in the bioactivation of multiple procarcinogens or the metabolism of multiple substrates including an array of xenobiotics and environmental carcinogens. 326 Lebanese women of whom 99 were cancer free (controls) and 227 were diagnosed with breast cancer (cases) were included. Blood for DNA was collected and medical charts were reviewed. Three genotyping methods were employed including: (1) restriction fragment length polymorphism (RFLP) for CYP2E1*5B, CYP2E1*6, NAT2*5 and NAT2*6; (2) gel electrophoresis for GSTM1 and GSTT1; and (3) real-time PCR for GSTP1 Ile/Val polymorphism. We analyzed the relationship between genetic susceptibilities in selected xenobiotic metabolizing genes and breast cancer risk. Allele frequencies were fairly similar to previously reported values from neighboring populations with relevant migration routes. There were no statistically significant differences in the distribution of variant carcinogen metabolizing genes between cases and controls even after adjusting for age at diagnosis, menopausal status, smoking, and alcohol intake. Despite its limitations, this is the first study that assesses the role of genetic polymorphisms in DMEs with breast cancer in a sample of Lebanese women. Further studies are needed to determine the genetic predisposition and gene-environment interactions of breast cancer in this population.