Orhan B

Primary neuroendocrine small cell carcinoma of the breast.

A 60-year-old Turkish woman presented with a left breast mass, which was considered for neoadjuvant chemotherapy. By the end of the treatment cycles, the tumor had decreased in size, and the patient underwent modified radical mastectomy with axillary lymph node dissection. Pathologic examination of the tumor revealed a small cell carcinoma with neuroendocrine features confirmed by immunohistochemical stains. Multiple axillary lymph nodes were involved by metastatic small cell carcinoma carrying the same morphologic characteristics noted in the primary breast tumor. We hereby present this case as a primary neuroendocrine small cell carcinoma of the breast. This entity occurs very rarely in the breast, and fewer than a dozen cases have been reported in the literature. Extrapulmonary small cell carcinoma of the breast is reportedly a very aggressive tumor for which no consensus for treatment has yet been drawn.

Erythropoietin Against Cisplatin-Induced Peripheral Neurotoxicity in Rats

Cisplatin (CDDP) is a potent anticancer drug, and neurotoxicity is one of its most important dose-limiting toxicities. In this study we investigated the role of recombinant human erythropoietin (rhuEPO) for protection against CDDP-induced neurotoxicity. All experiments were conducted on female Wistar-albino rats. Animals were randomly assigned to three groups. Group A received only CDDP, group B received CDDP plus rhuEPO, and group C received only rhuEPO. Electroneurography (ENG) was done in the beginning and at the end of 7 wk, then the rats were sacrificed and the sciatic nerve was removed for histopathological examination.The mean initial latency was 2.7438 ms in group A, 2.4875 ms in group B, and 2.62 ms in group C. After 7 wk of treatment, the latency was 2.4938, 2.6313, and 2.3900 ms, respectively. The difference in latencies was not statistically significant. The amplitude of compound muscle action potential (CMAP) was 12.8125 mV, 14.3875 mV, and 14.5600 mV before the treatment and 8.4875, 12.8250, and, 13.0800 mV after treatment, respectively. Amplitude of CMAP was significantly greater in rhuEPO-treated groups (groups B and C) compared to cisplatin only Group A. The mean area of CMAP was 12.2625, 12.3500, and, 12.2800 mV s before the treatment and 5.7125, 10.6463, and 9.1600 mV s after the treatment, respectively. The area of CMAP was significantly larger in rhuEPO-treated groups. In histopathological studies thick, thin, and total number of nerve fibers were 4053, 5050, and 9103, in group A, 5100, 8231, and 13331, in group B, and 5264, 6010, and 11274, in group C respectively. In the microscopic examination active myelinization process was observed in rhuEPO-treated groups. We concluded that at the given dose and schedule CDDP-induced motor neuropathy and rhuEPO prevented this neuropathy by sparing the number of normal nerve fibers and by protecting the amplitude and area of CMAP. We concluded that rhuEPO may also play a role in active myelinization and it is an active agent in protection against CDDP-induced peripheral neuropathy, warranting further clinical studies.

Protection against cisplatin-induced nephrotoxicity by recombinant human erythropoietin.

Cisplatin (CDDP) is a potent nephrotoxin, and nephrotoxicity is its most important dose-limiting toxicity. In this study, we aimed to investigate the role of recombinant human erythropoietin (rhEPO) in the protection of cisplatin-induced nephrotoxicity and compare its efficacy with the cell-protective agent amifostine. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to four groups, each including six rats. Group A received only CDDP, group B received CDDP plus rhEPO, group C received CDDP plus amifostine, and group D received only rhEPO. At the end of 7 wk, hemoglobin (Hgb), hematocrite (Htc), blood urea nitrogen (BUN), and creatinine (Cr) levels were determined and kidneys of the rats were removed. The weights of the kidneys were measured and sent for histopathological examination. Proximal tubules from four areas of the kidney (outer cortex, inner cortex, the medullary ray, and outer stripe of outer medulla [OSOM]) were evaluated. There were statistically significant differences among the groups in terms of tubular scores, including overall renal tubular score, cortex, inner cortex, OSOM, and medullary ray tubular scores, and Htc levels. Group A rats had the worse tubular scores in all categories when compared to group D rats. When the results of groups B and C were compared, there were no differences in terms of BUN, Cr levels, and tubular scores, but the Htc level was significantly higher in group B. Group B rats had better overall and OSOM tubular scores when compared to group A. Group C also had better overall and OSOM tubular scores compared to group A. The present study showed for the first time that rhEPO plays an important role in the prevention of cisplatin-induced nephrotoxicity and it is as effective as amifostine.

Protective effect of amifostine against cisplatin-induced motor neuropathy in rat.

Cisplatin (CDDP) is a potent anticancer drug. Neurotoxicity is one of the most important dose-limiting toxicity of CDDP. We investigated the role of amifostine in the protection against CDDP-induced neurotoxicity especially on the motor nerves. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to two groups, each including six rats. Group A received CDDP plus amifostine and Group B received CDDP only. Electroneurography (ENG) was carried out in the beginning and at the end of 7 wk; then, the rats were sacrificed and the sciatic nerve was removed for histopathological examination.The mean initial latency was 2.4667 msn for group A and 2.44833 msn for group B. After 7 wk of treatment, the latency was 2.9167 for group A and 2.6333 for group B. The difference in latencies was not statistically significant. The amplitude was 11.7853 mV and 13.533 mV for groups A and B, respectively. After 7 wk of treatment, the amplitude was 9.400 mV and 9.000 mV, respectively. The decrease of amplitude in compound muscle action potential (CMAP) was 20% in the amifostine group and the decrease was 33% in the untreated group. The mean area of the CMAP in group A was 9.400 mVsn initially and 9.666 mVsn at the end of the treatment; there was a 0.3% increase despite CDDP treatment. In group B, the mean area of the CMAP was 13.816 mVsn initially and 11.857 mVsn at the end of the treatment; this corresponded to a statistically significant 14% decrease as a result of CDDP treatment. The ENG and histopathological studies showed that at the given dose and schedule CDDP-induced motor neuropathy and amifostine reduced this neuropathy both by protection of the amplitude and area of the CMAP in ENG studies and by sparing a larger number of nerve fibers.

Comparison of radiation-induced oral mucositis scoring systems

Background A number of oral toxicity scoring systems have been described, but their direct comparison has rarely been undertaken and little data exists. An impediment to mucositis research has been the lack of an accepted, validated scoring system. The objective of this study was to design a test and validation of scoring systems. Materials and methods Forty-three patients with head and neck malignancies who had been irradiated were evaluated. Five different mucositis scoring systems (World Health Organization, Radiation Therapy Oncology Group, “Hickey”, “Van der Schueren” and “Makkonen”) were compared with each other. Results Daily mucositis scores demonstrated a high correlation among scoring systems (P <0.05 and coefficient of correlation κ and r = 0.5 - 0.95). Objective mucositis scores demonstrated a strong correlation with symptoms. Conclusions All scoring systems were equally valid. The exact grading of mucositis is achieved by combining clinical information about pain and nutritional status with oral mucosal reactions.

Acute Myeloblastic Leukemia Achieving Complete Remission with Amifostine Alone

Amifostine, a phosphorylated thiol-amine, is known as a cytoprotective agent especially for cisplatin containing chemotherapies. Apart from the cytoprotective role, Amifostine could also be used in the treatment of hematologic malignancies such as myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML), as a treatment option or for potentiating the effects of cytotoxic agents. We tried to use Amifostine in a patient with AML, which did not respond to conventional cytotoxic chemotherapy and aimed to publish the results. The patient was a 77-year-old male patient, he was diagnosed as AML by peripheral blood smear and bone marrow aspiration. Treatment commenced with low dose cytosine arabinoside (Ara-C) but the therapy should have ceased due to patient intolerance. The patient refused further therapy and he was offered to have Amifostine treatment. Amifostine was administered 200 mg/m 2 three times a week, with ciprofloxacin, pentoxifyllin and dexamethasone. Dramatic response was obtained after 8 weeks of administration. Blast rate was reduced from 35 to 7% in bone marrow aspiration; pancytopenia was restored to normal levels. This remission was maintained through 8 more weeks. Amifostine treatment was restarted after he relapsed but this time he did not respond to the treatment and died of gastrointestinal bleeding on the 8th week of treatment.

Recombinant Human Erythropoietin in the Treatment of Chronic Anemia of Cancer

Accessible online at: http://BioMedNet.com/karger We read the article of Mittelman et al. [1] on the treatment of multiple myeloma (MM)-associated anemia with recombinant human erythropoietin (EPO) with great interest. They treated 17 patients with MM and reported a response to EPO characterized by an increase in hemoglobin levels, a reduction of blood transfusion requirements and improvement in the performance status. They measured the pretreatment endogenous serum EPO levels and found them to be relatively low. Although studies have shown a decreased level of pretreatment serum EPO in MM, most of the patients in the study of Mittelman et al. were on systemic chemotherapy [1, 2]. It would have been better if EPO levels had been assessed before chemotherapy administration because the pretreatment endogenous serum EPO level is the most important factor for the prediction of the response to exogenous EPO [2–4]. In fact this is only true for patient groups not receiving any chemotherapy. Chemotherapy interferes with EPO levels as a result of unknown mechanisms, making a single EPO determination difficult to interpret and diminishing its predictive value [5, 6]. Performance status and reticulocyte response to EPO therapy after 4 weeks of treatment are the other predictors of response and a serum ferritin level of 1400 ng/ml after 2 weeks of EPO therapy strongly indicates unresponsiveness. The treatment results also vary depending on the type of cancer and the stage of disease [3, 4]. The effect of chemotherapy on the serum EPO level is not clearly understood [2–6]. We think this causes difficulty in the interpretation of the results achieved in the study of Mittelman et al. Some studies report a decreased EPO response to anemia in patients receiving chemotherapy, not being influenced by the presence or absence of cisplatin in the regimen [7, 8]. However in a recent study we investigated the effect of chemotherapy regimens on serum EPO levels in cancer patients and found increased serum EPO levels in patients receiving chemotherapy especially cisplatin [9]. In our study we also detected a higher serum EPO level in anemic patients aged above 50 compared to anemic patients aged below 50 [9]. Their study group consisted of patients with an advanced age with a median of 70 years. It is interesting that these quite old patients tolerated EPO very well. One would expect some cardiovascular side effects in the presence of increased viscosity due to hypergammaglobulinemia caused by MM. Although they report no correlation between the serum M component or the number of bone marrow plasma cells and the increase in the hemoglobin level, the study does not include a control group so it would be incorrect to relate the achievement of a better performance status to the correction of anemia by EPO. Instead the patients could have essentially benefited from the chemotherapy they received. It is clear that recombinant hematopoietic growth factors play a major role in the management of patients with cancer [3, 10]. Erythropoietin therapy can correct the anemia and can reduce the need for blood transfusions in certain cancer patient groups [2–4]. However, selection of those patients who will benefit from this therapy is critical for reasons of cost-effectiveness. OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO

Thrombotic Thrombocytopenic Purpura Associated with Ticlopidine

Thrombotic thrombocytopenic purpura is a syndrome characterized by hemolytic anemia, thrombocytopenia, neurological symptoms, fever and renal dysfunction. Although the syndrome is usually associated with various infections, vasculitis and pregnancy, rarely can it be associated with certain neoplasms and drugs such as ticlopidine. A 63-year-old woman, who had undergone coronary angioplasty and had been started on ticlopidine, was admitted to our clinic with a history of vomiting, fatigue, hematuria and deterioration in her cognitive abilities. Thrombotic thrombocytopenic purpura was diagnosed on the basis of neurological changes, an increase in LDH, urea, creatinine, indirect bilirubin levels, anemia and peripheral smear findings. Treatment was initiated with daily plasmapheresis and complete clinical and laboratory recovery developed. The patient was discharged after 14 days.

A Case of Cutaneous Diffuse Large B-cell Lymphoma.

Received/Gelis tarihi : June 10, 2013 Accepted/Kabul tarihi : September 4, 2013 To the Editor, We report the clinical findings of a 55-year-old woman who presented with purple-reddish nodules on her face diagnosed as primary cutaneous diffuse large B-cell lymphoma (PCLBCL), which is very rarely seen in this area. A 55-year-old woman applied to our oncology department after a brief episode of fever, general weakness, and erythematous patches and plaques in the facial area (Figure 1). Other associated symptoms and signs were general malaise and weight loss of 5 kg in 1 month. She had previously been well. A diagnostic biopsy showed an infiltration of large lymphoid cells staining positively for CD20, BCL-6, BCL-2, and PAX5, suggesting a diagnosis of diffuse large B-cell lymphoma (Figure 2). The cells were negative for CD5 and CD10. Renal and liver functions were normal. Bone marrow aspiration and biopsy showed no evidence of lymphoma. There was no other systemic organ involvement. The patient began receiving systemic chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. After 3 cycles of treatment, the large tumor showed no gradual improvement; this was suggestive of a lack of response. Rituximab plus ifosfamide, carboplatin, and etoposide chemotherapy (R-ICE) were therefore initiated. The patient was treated with 3 cycles of R-ICE chemotherapy. The patient declined additional treatment because her condition remained progressive despite the treatment, and she died soon after. Infomed consent was obtained. PCLBCL is a rare primary cutaneous lymphoma characterized by a diffuse proliferation of large B cells consisting of centroblasts and immunoblasts, occurring most commonly on the legs [1]. PCLBCL affects elderly population with a female predominance. This type of lymphomas tend to develop on the lower limbs, predominantly as large dermal nodules or tumors, which are either solitary or multifocal and rapidly enlarging [1]. PCLBCL can also rarely occur at other cutaneous sites [2]. The prognosis of PCLBCL is poor, with a 5-year survival of 41%-58%

Diagnosis and Management of Adrenocortical Carcinomas

Adrenocortical carcinomas (ACC) are rare tumors with unfavorable prognosis; they may be functional (hormone secreting) or nonfunctional. The estimated incidence is 1–2 per million per population and the overall 5-year survival is less than 40 %. Surgery is the mainstay of treatment in patients with localized disease, and metastasectomy can be performed in selected cases. Mitotane is a derivative of the insecticide dichlorodiphenyltrichloroethane and has been used in adjuvant, locally advanced, and metastatic setting in the treatment of ACC. Adjuvant therapy with mitotane after surgical excision is recommended in high-risk cases. In metastatic or unresectable disease, mitotane can be used alone or in combination with chemotherapy. Radiotherapy is usually utilized with palliative intent; recent retrospective studies also showed benefit of postoperative radiotherapy. Targeted therapies with tyrosine kinase inhibitors, vascular endothelial growth factor receptor inhibitors, or mTOR inhibitors alone or in combination are still under investigation.