A phase II trial of 10-ethyl-10-deaza-aminopterin, a novel antifolate, in patients with advanced and/or recurrent squamous cell carcinoma of the head and neck. The EORTC Head and Neck Cancer Cooperative Group.

Forty-seven patients with advanced and/or recurrent squamous cell carcinoma of the head and neck were treated with 10-ethyl-10-deaza-aminopterin (10-EdAM), a new analogue of methotrexate. The drug was given as a weekly i.v. bolus injection, starting at 80 mg/m2 with two dose increments of 10% if no toxicity was observed after two weeks. Only patients with tumors of the larynx, oral cavity, oropharynx and hypopharynx were included in the trial. Eighty-two percent of the patients had had prior surgery and/or radiotherapy. Forty-four patients were evaluable for response and toxicity. Five CR (12%) and five PR were obtained, yielding a response rate of 24% (CR+PR). The toxicity was similar to that usually seen with methotrexate; stomatitis and skin toxicity were rather pronounced. The data suggest that 10-EdAM has activity similar to that of methotrexate in patients with head and neck cancer.     

Feasibility study of high-dose carboplatin and etoposide in the salvage treatment of testicular cancer.

Eleven patients with testicular cancer, either relapsing after or refractory to cisplatin-based chemotherapy, underwent salvage chemotherapy with high-dose carboplatin (800 mg/m2 on day 1) and high-dose etoposide (500 mg/m2 on days 1, 3 and 5). A total of 21 courses were administered. The major toxicity consisted of profound myelosuppression. There were two toxic deaths, both caused by infection during neutropenia. Bone marrow recovery was usually complete around day 26 (range 19-129). Other toxicities included mild mucositis, nausea and vomiting, and alopecia. No significant neurotoxicity or hearing loss were observed and only one patient had a moderate decrease in renal function. Nine of ten evaluable patients responded, with one complete remission, 6 partial remissions with normalization of tumor markers, and two partial remissions with over one log decrease of tumor markers. The duration of these remissions was not evaluable, since only three evaluable and responding patients did not receive additional therapy after HD-CE. All three relapsed after discontinuing chemotherapy. HD-CE has activity in relapsing or refractory testicular cancer and can be administered without bone marrow support. The regimen may thus be suitable to be used as a remission induction regimen prior to consolidation with intensive chemotherapy and autologous bone marrow transplantation.     

Retrograde Inversion Stripping as a Complication of the Clarivein? Mechanochemical Venous Ablation Procedure

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein^® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein^® device, without adverse sequelae.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.     

Pelvic ultrasound findings in different forms of sexual precocity

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal–cervical ratio. Ovarian volume was also significantly increased in thelarche and thelarche variant. The fundal–cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.     

Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for histologically proven lymph node positive bladder cancer

PURPOSE: We gained insight into the effect of neoadjuvant chemotherapy and subsequent surgery in patients with bladder cancer with tumor positive lymph nodes. MATERIALS AND METHODS: A total of 52 patients with histologically proven positive lymph nodes (by lymph node dissection or aspiration cytology) were treated with chemotherapy and post-chemotherapy surgery in case of partial or complete response. We evaluated response in the primary tumor and lymph nodes, long-term clinical outcome, and clinicopathological features potentially predictive of survival. RESULTS: Complete response, partial response and stable/progressive disease were attained in 29%, 57% and 14%, and resulted in a 5-year survival of 42%, 19% and 0%, respectively. Objective response (HR 4.1), especially complete response (HR 8.0), was independently associated with survival. The prognostic values of lymph node status and bladder tumor status after methotrexate, vinblastine, doxorubicin and cisplatin were evaluated separately. A tumor negative bladder combined with tumor negative nodes were associated with improved survival (HR 4.4) as was a tumor negative lymph node region in the presence of residual bladder disease (HR 2.8). All patients with post-chemotherapy tumor positive nodes died within 2 years. In resected specimens residual disease was found in 4 of 15 clinically complete responders while no tumor could be detected in 3 of 29 clinically assessed as partial responders. CONCLUSIONS: Response to chemotherapy is associated with improved survival, and our data suggest that lymph node status after methotrexate, vinblastine, doxorubicin and cisplatin is more important than local tumor status in this aspect. In the absence of reliable noninvasive methods, post-chemotherapy surgery in this series was the most adequate method of response evaluation and in limited partial responders led to long-term progression-free survival.     

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide,thiotepa, carboplatin): the Netherlands Cancer Institute experience

High-dose chemotherapy (HD-CT) has a role in the potentially curative treatment of several tumours. The relative efficacies of the different regimens have not been studied in comparative trials, but it is clear that toxicities differ significantly between them. We analysed the immediate and long-term toxicity in the first 100 consecutive patients treated with the CTC regimen (cyclophosphamide 6000 mg m(-2), carboplatin 1600 mg m(-2) (or 20 mg ml(-1) min under the curve (AUC)) both as daily 1 h infusion, thiotepa 480 mg m(-2) as twice daily 30 min infusion, all divided over 4 consecutive days) followed by peripheral blood progenitor cell reinfusion (PBPC-Tx). Most patients had high-risk (n=86) or metastatic (n=4) breast cancer, or a germ cell tumour (n=8). Two patients (with a medulloblastoma and an aesthesioneuroblastoma, respectively) received CTC as off-protocol salvage regimen. The main toxicity was bone marrow suppression. Most patients had PBPC-Tx with granulocyte colony-stimulating factor (G-CSF), and the median time to neutrophil count 500 x 10(6) l(-1) and platelet count >20 x 10(9) l(-1) without transfusion independence was 10 (range 8-25) and 13 (8-60) days, respectively. The toxic death rate was 1%. Other frequent toxicities were neutropenic fever requiring antibiotics (n=65), central catheter-related infection (n=12) or a bleeding episode (n=48), mostly epistaxis (n=26). Reversible cardiac toxicity was seen in six patients and pulmonary events occurred in seven patients (infection (n=6), embolism (n=1)). Grade 3-4 gastrointestinal toxicity was frequent: nausea and vomiting 55%, diarrhoea 28% and mild liver toxicity (transaminase elevations) 9%. One patient pretreated with cisplatin had a kidney transplantation 8 years after HD-CT. Late complications included reversible radiation pneumonitis (n=12) and chronic heart failure (n=2). We found five second solid malignancies and two myelodysplasias. In conclusion, the CTC regimen is associated with a moderate, mainly reversible, toxicity. Future studies need to compare the efficacy and toxicity of the different HD-CT regimens.     

The patient-physician relationship. Patient-physician communication during outpatient palliative treatment visits: an observational study

Context  Improving health-related quality of life (HRQL) is an important goal of palliative treatment, but little is known about actual patient-physician communication regarding HRQL topics during palliative treatment. Objectives  To investigate the content of routine communication regarding 4 specific HRQL issues between oncologists and their patients and to identify patient-, physician-, and visit-specific factors significantly associated with discussion of such issues. Design  Observational study conducted between June 1996 and January 1998. Setting  Outpatient palliative chemotherapy clinic of a cancer hospital in the Netherlands. Participants  Ten oncologists and 240 of their patients (72% female; mean age, 55 years) who had incurable cancer and were receiving outpatient palliative chemotherapy. Main Outcome Measures  Patient and physician questionnaires and audiotape analysis of communication regarding daily activities, emotional functioning, pain, and fatigue during an outpatient consultation using the Roter Interaction Analysis System. Results  Physicians devoted 64% of their conversation to medical/technical issues and 23% to HRQL issues. Patients' communication behavior was divided more equally between medical/technical issues (41%) and HRQL topics (48%). Of the independent variables investigated, patients' self-reported HRQL was the most powerful predictor of discussing HRQL issues. Nevertheless, in 20% to 54% of the consultations in which patients were experiencing serious HRQL problems, no time was devoted to discussion of those problems. In particular, these patients' emotional functioning and fatigue were unaddressed 54% and 48% of the time, respectively. Discussion of HRQL issues was not more frequent in consultations in which tumor response was evaluated. Conclusion  Despite increasing recognition of the importance of maintaining patients' HRQL as a goal of palliative treatment, the amount of patient-physician communication devoted to such issues remains limited and appears to make only a modest contribution, at least in an explicit sense, to the evaluation of treatment efficacy in daily clinical practice.      

Save or destroy? The importance of medical record for former patients and future patients

In 1995, a new privacy law was introduced in the Netherlands. According to this law, medical records should be saved for 10 years, and then destroyed, unless keeping the records for a longer period follows reasonably from the duties of the treating physician (as is the case, for example, when treating patients with a chronic disease). There are serious concerns with regard to the future availability of medical record data for clinical research and patient care after 2005. Evaluation of the late effects of many medical treatments will no longer be possible in the Netherlands. Patient care, particularly genetic counselling, will be also seriously compromised. As a possible solution the profession might name diagnoses and treatments regarding for which, from the point of view of good care, it is necessary for files to be kept for longer than 10 years. For a uniform nationwide policy it would be better if all files, perhaps after sorting by diagnosis and treatment, should be obligatorily kept for much longer than 10 years, preferably for the duration of the life expectancy.