Athanasios Karabelis

Intramedullary spinal cord metastases from atypical small cell lung cancer : A case report and literature review

Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly progressing systemic malignancy. Lung cancer represents the most common solid tumor associated with the development of ISCM. We describe a 47-year-old female with atypical small cell lung cancer (SCLC) developing ISCM. After a thoracoscopic biopsy she was treated with combination chemotherapy consolidated by mediastinal radiotherapy leading to complete remission. Three months later, she developed a Brown-Sequard syndrome and an MRI scan revealed ISCM at the T10–T12 levels, and secondary brain lesions. Despite treatment with steroids and thoracic spine/brain radiotherapy, no recovery of her motor function was seen and she died 4 months later due to progressive disease in the CNS. The present case, adds to the existing list of ISCM cases reported so far for lung cancer, undermine the ominous prognosis and limited treatment options available, and an extensive literature overview and discussion of similar cases is provided.

Changes of cerebrospinal fluid tumor marker levels may predict response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer

The aim of the present study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. CSF tumor marker levels correlated with response to treatment and outcome in each patient, and, despite achieving negative CSF cytology after therapy in two patients, it heralded disease progression. Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.

Comparison of ondansentron (GR 38032F) versus ondansentron plus alprazolam as antiemetic prophylaxis during cisplatin-containing chemotherapy.

The purpose of our study was to evaluate the effectiveness of alprazolam (APZ) as an adjuvant drug to ondasentron against cisplatin-induced emesis. All patients received CDDP 100 mg/m2, and had previously received chemotherapy. We established two groups of patients randomly: Group A patients received 5-HT, alone, and Group B received 5-HT3 and APZ. The drugs were administered as follows: 5-HT3 was given at a dose of 1 ampule 8 mg in 100 ml N/S in 10 minutes IV infusion before the infusion of CDDP. We continued with 1 tablet 8 mg in the afternoon and 1 before sleeping the first day; for the next two days, patients received 3 tablets 8 mg/day. APZ was given in tablets of 0.25 mg 60 minutes before CDDP infusion and then with the second and third dose of 5-HT3. We did not find significant differences in clinical parameters and factors, especially anxiety, that influenced vomiting between the examined groups. The mean number of vomiting episodes without gastric content (4.76 episodes) and the mean duration of nausea (195 minutes), were greater in Group A than in Group B (1.39 episodes. p < .0001; 91 minutes, p < .049). Differences also were found in the mean number of vomiting episodes with gastric content between the examined groups (A: 1.97; B: 1.09; p < .135). The intense of nausea and vomiting according to WHO classification was greater in Group A (grade 0, p < .004; grade 2, p < .020) than in Group B. Patients of Group B had fewer problems with appetite (p < .027), and more intense sedative effect (grade 0 [p < .001], 1 [0.027], 2 [0.022]) than patients of Group A. In conclusion APZ improved the antiemetic efficacy of ondasentron in cisplatin-induced emesis.

Comparison of two oral regimens for the outpatient treatment of low-risk cancer patients with chemotherapy-induced neutropenia and fever: Ciprofloxacin plus cefuroxime axetil versus ciprofloxacin plus amoxicillin/clavulanate

The objective of this investigation was to assess retrospectively the safety and the efficacy of oral ciprofloxacin plus cefuroxime axetil compared to the combination of oral ciprofloxacin plus amoxicillin/clavulanate, as initial outpatient treatment, in low-risk cancer patients with fever and neutropenia. We analysed retrospectively 120 episodes of febrile neutropenia, treated on an outpatient basis at 2 different oncology units; 63 episodes were treated with the oral regimen of ciprofloxacin plus amoxicillin/clavulanate and 57 were treated with the combination of oral ciprofloxacin plus cefuroxime. 20 treatment failures were recorded–2 of them among patients receiving ciprofloxacin plus amoxicillin/clavulanate and 18 in the ciprofloxacin plus cefuroxime group. Univariate analysis showed that the administration of ciprofloxacin plus cefuroxime was associated with a worse outcome compared to the regimen ciprofloxacin plus amoxicillin/clavulanate (OR 11, CI 2.42–49.9, p =0.002). In the multivariate model, after adjusting for the absolute number of neutrophils and the duration of neutropenia, the effect of the antibiotic regimen on the outcome disappeared, and no significant differences between the 2 regimens were noted, although the regimen of ciprofloxacin plus cefuroxime was associated with a trend to a worse outcome (OR 4.74, CI 0.72–31.1, p =0.10). In conclusion, the 2 regimens appeared equally safe and effective but prospective studies are needed to confirm these results.

Rare and aggressive metastatic, axial multifocal local epithelioid sarcoma associated with paraneoplastic granulocytosis and hypoglycaemia

Epithelioid sarcoma is a rare soft-tissue sarcoma (STS; <1% of total STS) that aff ects young, usually male, adults or adolescents. In most cases, the sarcoma grows slowly (over a period of years), involves the dermis, subcutis, or deeper soft tissues in the distal extremities in 55–60% of cases. Epithelioid sarcoma is characterised by diagnostic diffi culties, both clinically and histopathologically, which results in a high frequency of initial misdiagnosis and loss of crucial treatment time. Surgical excision (amputation or wide en-bloc excision), then high-dose radiotherapy represents optimum treatment, however, this regimen is associated with a recurrence rate of 77% and a median overall survival of about 88 months for patients without distant metastases, and just 8 months for those with distant metastases. Unlike in most sarcomas, metastases aff ecting the lymph nodes are common in epithelioid sarcoma. However, the lungs are the most common site of distant metastases in epithelioid sarcoma. Furthermore, multifocal local disease, initial proximal limb or axial tumour location, regional metastases, high mitotic fi gures, necrosis, and haemorrhage or vascular invasion have a more aggressive course, and predict for a poor survival that is free from distant metastasis. Immunohistochemically, most epithelioid sarcoma express vimentin, keratin, epithelial membrane antigen (EMA), CD34 (60%), cyclin D1 and tissue polypeptide antigen (TPA). Coexpression of vimentin and keratin is thought to be characteristic of epithelioid sarcoma. A 37-year-old man was admitted to our hospital diagnosed with epithelioid sarcoma. On admission, the patient had four cutaneous lesions measuring 3–6 cm and a painful right knee. The lesions were localised at the epigastrium, right lateral abdominal area, anterior iliac crest level, spinal region at the level of L3–L5, and right buttock. According to the patient’s recent medical history, the fi rst lesion of around 1 cm seemed to develop on a surgical scar 3 months after a gastric ulcer operation. The lesion was misdiagnosed as infl ammation and was treated with antibiotics. 1 month later, a second lesion developed on his right buttock, and a biopsy by surgical excision yielded a diagnosis of epithelioid sarcoma. Microscopic examination shows nodular growth with central necrosis and haemorrhage (fi gure 1A). Immunohistochemistry showed expression of vimentin (fi gure 1B) and actin. EMA, keratin, CEA, S100p, CD30, CD31, and CD34 were negative. CT scans of the thorax and abdomen, and a bone scan found splenomegaly, multiple lung nodules, enlarged mediastinal, mesenteric, and paraortic lymph nodes, and bone metastases at L3, L5 vertebrae and at the right upper tibia (fi gure 2). Blood analyses showed leucocytosis (white blood cell [WBC] count: 23·9 × 10 cells/L; with neutrophils: 87·9%). Multiple cultures of blood, urine, sputum, and dermal lesions found no evidence of infection during the patient’s clinical course. Based on prominent leucocytosis, we measured serum granulocyte colony-stimulating factor (G-CSF). The highly increased serum G-CSF of more than 2 μg/L (normal <40 ng/L) suggested that a G-CSF-producing epithelioid sarcoma was the cause of leucocytosis. The Lancet Oncol 2006; 7: 82–84

Malignant peripheral nerve sheath tumor in neurobifromatosis type-1: two case reports

IntroductionMalignant peripheral nerve sheath tumors are rare soft tissue sarcomas. They are considered to carry a poor prognosis with current therapeutic approaches. Successful treatment depends on a multimodal approach.Case presentationThe authors report two cases with malignant peripheral nerve sheath tumors arising from pre-existing neurofibromas in the grounds of neurofibromatis-type I. Complete surgical removal of all lesions is considered before and after induction chemotherapy. Correlation of the response to chemotherapy in the context of the immuno-histopathological features of the tumors is also discussed with reference to the existing literature.ConclusionA need for a multidisciplinary approach with chemotherapy, surgery and radiotherapy is anticipated in the management of malignant peripheral nerve sheath tumors as described in these two reported cases. It is felt that further research on the molecular aspects of malignant peripheral nerve sheath tumors and neurofibromatis-type I will optimize treatment strategies in the future.

A Phase II Study of the Docetaxel- Ifosfamide-Carboplatin Combination in Advanced Non-Small-Cell Lung Cancer

Purpose: In the present phase II study we evaluated the docetaxel-ifosfamide-carboplatin (DICb) combination in the outpatient setting in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with advanced NSCLC (stages IIIB/IV), WHO performance status (PS) <2, and no prior chemotherapy were eligible. Chemotherapy drug doses were: docetaxel: 80 mg/m2, ifosfamide: 3.5 g/m2, and carboplatin at a target area under the curve of 5 (based on Calvert’s formula), all on day 1, followed by prophylactic G-CSF. Results: Fourty patients were entered and all are evaluable for response and toxicity: median age: 64 (48–72); PS: 1 (0–1); gender: 29 males/11 females; stages: IIIB: 13 (33%), IV: 27 (67%). Metastatic sites at diagnosis included: lymph nodes: 25; bone: 7; liver: 4; brain: 5; lung nodules: 13; adrenals: 6. Responses were as follows: 22/40 [55%; 95% confidence interval (CI), 54–81%] evaluable patients responded: 4 complete responses, 18 partial responses, 11 had stable disease, and 7 had progressive disease. The median response duration was 7 months (range 2–14 months), median time to progression 9 months (range 2–18 months) and median overall survival 11 months (range 3–46+ months). 1-year survival was 47.5%. Grade 3/4 toxicities included: neutropenia 28/40, with 12 developing grade 4 and 12% febrile neutropenia, thrombocytopenia grade 3: 3/40 and grade 4: 1/40, no grade 3 neuropathy, grade 1 CNS toxicity in 3, no renal toxicity, 8 grade 2 diarrhea and 4 grade 3 vomiting. Conclusion: In the present phase II study the DICb combination yielded important activity and good tolerability in advanced NSCLC.

Diffuse calcification of metastases after intensive multiagent chemotherapy in widespread osteosarcoma leading to death in a 18-year-old male: report of a case and literature review.

Multifocal osteosarcoma represents a rare and aggressive type of osteosarcoma in which multiple bone lesions are detected simultaneously in the absence of pulmonary or any other visceral organ involvement. Despite a multidisciplinary approach, overall survival remains poor and disease progresses, leading to death within 1 yr of diagnosis. Here we report a case of an 18-yr-old patient with extensively metastatic osteosarcoma developing diffuse calcification in lung, pleural, diaphragm, pericardial, subcutaneous metastases, and mediastinal lymph nodes after intensive multiagent chemotherapy. We provide an extensive review of the literature together with presentation of different aspects regarding the debate on the multicentric versus metastatic hypotheses for multifocal osteosarcoma. An update on the current understanding of the molecular features of this disease is also included.