A novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles to treat advanced squamous cell carcinoma of the tongue: preliminary findings

OBJECTIVE: The purpose of our study was to evaluate the effectiveness of intraarterial infusion of paclitaxel incorporated into human albumin nanoparticles for use as induction chemotherapy before definitive treatment of advanced squamous cell carcinoma of the tongue. SUBJECTS AND METHODS: Twenty-three previously untreated patients (age range, 27-75 years) who had carcinoma of the tongue (stage T3-T4, any N) received intraarterial therapy with paclitaxel incorporated into albumin nanoparticles delivered by transfemoral catheterization into the external carotid artery (10 patients), selectively into the lingual artery (12 patients), or into a faciolingual trunk (1 patient). Each patient received two to four infusions, with a 3-week interval between infusions. The dose administered was 230 mg/m(2) in eight patients, 180 mg/m(2) in six patients, and 150 mg/m(2) in nine patients. Sixteen patients underwent surgery. Of these 16 patients, eight subsequently received radiotherapy, and three received a combination of chemotherapy and radiotherapy. Of the remaining seven patients, one received chemotherapy alone, four received radiotherapy alone, one received chemotherapy plus radiotherapy, and one refused any further treatment. RESULTS: Sixty-seven infusions were performed successfully. Eighteen patients (78%) had a clinical and radiologic objective response (complete, 26%; partial, 52%). Three patients (13%) showed stable disease, and two (9%) showed disease progression. The four patients with complete clinical response who underwent surgery showed microscopic residual carcinoma measuring less than 1 mm in two patients, less than 5 mm in one patient, and less than 1 cm in one patient. The toxicities encountered were hematologic (grade 3) in two patients (8.6%) and neurologic (grade 4) in two patients (reversible paralysis of the facial nerve, 8.6%). Two catheter-related complications occurred: one reversible brachiofacial paralysis and one asymptomatic occlusion of the external carotid artery. CONCLUSION: Intraarterial infusion of paclitaxel in albumin nanoparticles proved reproducible and effective and deserves further investigation as induction chemotherapy before definitive treatment of advanced tumors of the tongue, with a view to organ preservation.     

Special Feature: Complex Systems: From Chemistry to Systems Biology Special Feature: Phenotypes and tolerances in the design space of biochemical systems

One of the major unsolved problems of modern biology is deep understanding of the complex relationship between the information encoded in the genome of an organism and the phenotypic properties manifested by that organism. Fundamental advances must be made before we can begin to approach the goal of predicting the phenotypic consequences of a given mutation or an organism''s response to a novel environmental challenge. Although this problem is often portrayed as if the task were to find a more or less direct link between genotypic and phenotypic levels, on closer examination the relationship is far more layered and complex. Although there are some intuitive notions of what is meant by phenotype at the level of the organism, it is far from clear what this term means at the biochemical level. We have described design principles that are readily revealed by representation of molecular systems in an appropriate design space. Here, we first describe a generic approach to the construction of such a design space in which qualitatively distinct phenotypes can be identified and counted. Second, we show how the boundaries between these phenotypic regions provide a method of characterizing a system''s tolerance to large changes in the values of its parameters. Third, we illustrate the approach for one of the most basic modules of biochemical networks and describe an associated design principle. Finally, we discuss the scaling of this approach to large systems.     

Stereotactic excisional breast biopsy performed by interventional radiologists using the advanced breast biopsy instrumentation system

The Advanced Breast Biopsy Instrumentation (ABBI) system, which uses surgical cannulas up to 20 mm in diameter, is an alternative to conventional surgical biopsy for the diagnosis of non-palpable breast lesions. Since the need for radiological skill outweighs the surgical content of the technique, we evaluated the feasibility of complete management of the procedure by interventional radiologists. 35 of the 111 patients originally scheduled for the procedure were excluded, three because the lesion could not be visualized and 32 because of insufficient thickness of the compressed breast. The procedure had to be abandoned in one case due to a technical failure. 77 stereotactic excisional breast biopsy procedures were performed using the ABBI system in 75 patients with suspicious non-palpable mammographic lesions. The procedure was carried out under local anaesthesia in the radiology department, using a dedicated Lorad (R) radiographic system. 31 (40%) masses without calcifications, 11 (14%) masses with calcifications and 35 (46%) clusters of microcalcifications without tumour mass were sampled. 43 (56%) benign lesions and 34 (44%) malignant lesions were diagnosed. The overall mean diameter of the lesions was 8.7 mm (range 3-22 mm). All 34 patients with malignancies and lobular carcinoma in situ subsequently underwent surgery, the results of which are reported. Three (4%) haematomas were detected and aspirated percutaneously. Two technical problems occurred: an ABBI cannula malfunction, and a computer failure of the digital imaging system during the procedure. The average procedure time was 80 min and the cost of each procedure was 2,800,000 Italian lire (1555 US$). It is concluded that tissue sampling with the ABBI system can be performed entirely by radiologists without significant problems. The procedure was well tolerated by all patients. The quality of the biopsy specimen was identical to that of a surgical specimen but with the advantages of stereotactic precision for localization of the lesion.     

Chronic Active Hepatitis and Pregnancy: A Report of Two Cases in Adolescence

The course and outcome of pregnancy in two adolescents with chronic active hepatitis is described. Pregnancy was uneventful in both patients apart from mild biochemical deterioration in one patient. Both infants are entirely normal. One mother died 4 1/2 months after delivery from primary pulmonary hypertension, an extrahepatic manifestation of her chronic active hepatitis. The second patient is asymptomatic but bas evidence of ongoing liver disease 26 months postdelivery.     

Percutaneous computed tomography-guided radiofrequency thermal ablation of small unresectable lung tumours.

The aim of the current study was to evaluate the safety and the efficacy of radiofrequency thermal ablation (RFTA) for the treatment of nonsmall cell lung cancer (NSCLC) and isolated pulmonary metastases (METs) from colorectal cancer (CRC). A total of 31 patients (15 with NSCLCs and 16 with CRC lung METs), with 36 lung tumour nodules (mean+/-sd diameter: 22+/-8 mm, range: 10-35 mm) underwent computed tomography (CT)-guided RFTA using expandable electrodes. Contrast-enhanced CT was performed before and after (immediately and 30+/-5 days) each RFTA session to assess immediate results and complications and repeated 3 and 6 months post-RFTA, as well as every 6 months thereafter, to evaluate long-term results. Complete radiological necrosis was defined as a nonenhancing area at the tumour site that was equal to or larger than the treated tumour; persistence of enhancement at the tumour site indicated incomplete treatment. Local recurrence was defined as an increase in tumour size and/or enhancing tissue at the tumour site. Complete radiological necrosis of the 36 tumours was achieved with 39 RFTA sessions and 42 electrode insertions. No major complications or deaths were observed. Six patients experienced mild-to-moderate pain during the procedure. There were five cases of pneumothorax, none requiring drainage and four cases of pneumonia, which were successfully treated with antibiotics. After a mean follow-up of 11.4+/-7.7 months (range of 3-36 months), the overall local recurrence rate was 13.9% (20 and 9.5% for NSCLC and CRC-METs patients, respectively). Nineteen of the 31 (61.3%) patients were alive (15 apparently disease free) and 12 (38.7%) had died (three from causes unrelated to their cancer). Radiofrequency thermal ablation seems to be a safe, effective method for producing complete ablation of small nonsmall cell lung cancers and pulmonary colorectal cancer metastases.     

Surgical approach to isolated mediastinal lymphoma

With the aim of assessing the role of surgery in the management of isolated mediastinal lymphoma, we have reviewed the data of 123 operations performed on 102 patients (64 with Hodgkin's disease and 38 with non-Hodgkin's lymphoma). One death and four major complications occurred in these patients. Macroscopically radical resection was performed in 14 patients who are free of disease after 1 to 14 years. Debulking resection was performed in five patients: Three are alive after 5 to 11 years and two died after 36 and 40 months. Ten patients (seven with non-Hodgkin's lymphoma and three with Hodgkin's disease) had residual mediastinal masses of more than 2 cm after chemotherapy; to assess the nature of the lesion (fibrosis or residual disease), we subjected these patients to surgical restaging of the mediastinum: Results were negative in seven and positive in three. We conclude that open biopsy is indispensable to obtain good tissue specimens suitable for histologic and immunohistochemical assessment. Biopsy must be performed as a major surgical procedure to avoid reoperation: Mediastinoscopy and sternal splitting incisions proved the most reliable approaches. Locally radical or debulking resection might be considered in selected cases to enhance long-term results.     

Prevention and treatment of cardiovascular disease in Ethiopia: a cost-effectiveness analysis

Background

The coverage of prevention and treatment strategies for ischemic heart disease and stroke is very low in Ethiopia. In view of Ethiopia’s meager healthcare budget, it is important to identify the most cost-effective interventions for further scale-up. This paper’s objective is to assess cost-effectiveness of prevention and treatment of ischemic heart disease (IHD) and stroke in an Ethiopian setting.

Methods

Fifteen single interventions and sixteen intervention packages were assessed from a healthcare provider perspective. The World Health Organization’s Choosing Interventions that are Cost-Effective model for cardiovascular disease was updated with available country-specific inputs, including demography, mortality and price of traded and non-traded goods. Costs and health benefits were discounted at 3 % per year. Incremental cost-effectiveness ratios are reported in US$ per disability adjusted life year (DALY) averted. Sensitivity analysis was undertaken to assess robustness of our results.

Results

Combination drug treatment for individuals having >35 % absolute risk of a CVD event in the next 10 years is the most cost-effective intervention. This intervention costs US$67 per DALY averted and about US$7 million annually. Treatment of acute myocardial infarction (AMI) (costing US$1000–US$7530 per DALY averted) and secondary prevention of IHD and stroke (costing US$1060–US$10,340 per DALY averted) become more efficient when delivered in integrated packages. At an annual willingness-to-pay (WTP) level of about US$3 million, a package consisting of aspirin, streptokinase, ACE-inhibitor and beta-blocker for AMI has the highest probability of being most cost-effective, whereas as WTP increases to > US$7 million, combination drug treatment to individuals having >35 % absolute risk stands out as the most cost-effective strategy. Cost-effectiveness ratios were relatively more sensitive to halving the effectiveness estimates as compared with doubling the price of drugs and laboratory tests.

Conclusions

In Ethiopia, the escalating burden of CVD and its risk factors warrants timely action. We have demonstrated that selected CVD intervention packages could be scaled up at a modest budget increase. The level of willingness-to-pay has important implications for interventions’ probability of being cost-effective. The study provides valuable evidence for setting priorities in an essential healthcare package for CVD in Ethiopia.

     

Leiomyoma of the esophagus

Leiomyoma of the esophagus was surgically treated in 15 patients in 1962-1987. Six patients were asymptomatic and nine presented with dysphagia alone or combined with retrosternal pain, vague thoracic discomfort, dyspnea and cough, or palpitations. Barium swallow and esophagoscopy provided the correct diagnosis preoperatively in most cases. Transthoracic enucleation of the tumor was performed via right thoracotomy in nine patients and left thoracotomy in six. The location of tumor was the upper third of the thoracic esophagus in three cases, middle third in six and lower third in six cases. There was no surgical mortality or morbidity. Surgical removal of esophageal leiomyoma thus gave relief of symptoms, with minimal risk and excellent functional outcome.