Laryngeal cancer and smoking

The smoking habits of 109 male patients with laryngeal cancer were analysed. Two-thirds were heavy smokers. There was one non-smoker. In 12 cases, stopping smoking did not prevent the onset of cancer. Alcohol appears to be a contributing factor. Recent studies have suggested that lowered patient immunity and the herpes virus may be important aetiological factors.     

Laryngeal tuberculosis and laryngeal cancer

The primary objective of this study was to determine whether the development of behavioral sensitization to the putative dopamine D3 receptor agonist 7-OH-DPAT could be prevented by either selective D1-type or D2-type dopamine receptor antagonists. In three experiments, male Wistar rats (250-350 g) were given seven to nine injections (at 48-h intervals) of 7-OH-DPAT (1.0 mg/kg, SC) or vehicle in combination with the D2-type dopamine antagonist eticlopride (0.3 mg/kg, SC), the D1-type dopamine antagonist SCH 23390 (0.1 or 0.2 mg/kg, SC), or vehicle. After the injections, the rats were tested for locomotor activity in photocell arenas for 2 h. In the first two experiments, after seven injections, all rats were tested for activity following vehicle injections to test for possible conditioning effects. In each experiment, after the last pre-exposure session, all rats were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) and tested for activity. Major findings were as follows: a) 7-OH-DPAT treatments produced a progressively greater increase in locomotor activity with repeated treatment; b) concurrent treatment with eticlopride or SCH 23390 (0.1 and 0.2 mg/kg) blocked the acute locomotor-activating effects of 7-OH-DPAT across days; c) eticlopride, but not SCH 23390, completely blocked the development of behavioral sensitization to 7-OH-DPAT. Although the low dose of SCH 23390 (0.1 mg/kg) produced a partial attenuation of sensitization, the higher dose (0.2 mg/kg) of SCH 23390 appeared to augment, rather than block, sensitization to 7-OH-DPAT; d) rats previously treated with SCH 23390 (0.2 mg/kg, but not 0.1 mg/kg) without 7-OH-DPAT displayed a hyperactive response to the 7-OH-DPAT challenge injection; and e) after vehicle injections, rats previously given 7-OH-DPAT, SCH 23390, or eticlopride either alone or in combination were more active than vehicle control rats. These findings suggest that the neurochemical mechanisms mediating the development of behavioral sensitization to 7-OH-DPAT may differ from those of other dopamine D2-type agonists such as quinpirole or bromocriptine. Moreover, these results demonstrate that hyperactivity responses following vehicle injections in drug-pretreated animals do not necessarily reflect conditioning mechanisms.     

Treatments for newly diagnosed advanced ovarian cancer: analysis of survival data and cost-effectiveness evaluation

The main therapeutic options currently available for patients with newly diagnosed advanced ovarian cancer include: (i) cisplatin-based chemotherapy at conventional doses without paclitaxel, (ii) paclitaxel+cisplatin at conventional doses and (iii) high-dose chemotherapy with autologous hematopoietic rescue. After conducting a literature search to identify large-scale clinical trials based on these three therapeutic modalities, we carried out an analysis of the survival data and evaluated the cost-effectiveness ratio where appropriate. Cost data were obtained from published information. Effectiveness was estimated by determining the values of mean lifetime survival (MLS). Our analysis included a total of 15 clinical trials. The values of MLS were 3.05 years per patient for cisplatin-based chemotherapy at conventional doses without paclitaxel (1931 patients), 2.95 years per patient for chemotherapy with paclitaxel+cisplatin at conventional doses (184 patients) and 5.76 years per patient for high-dose chemotherapy with autologous hematopoietic rescue (53 patients). As compared with cisplatin-based chemotherapy without paclitaxel, high-dose treatments with hematopoietic rescue yielded a significantly better survival. Using cisplatin-based chemotherapy as a reference term, the incremental cost-effectiveness ratio for high-dose treatments was $25641 per life year gained (discounted dollars per discounted life year gained). Sensitivity testing suggested that the ratio remained below $50000 under most circumstances. We conclude that in the treatment of patients with advanced ovarian cancer, high-dose chemotherapy with hematopoietic rescue seems to be more effective and more cost-effective than standard treatments with cisplatin-based regimens at conventional doses.     

United Kingdom Cancer Research Campaign approach to quality-of-life research in cancer clinical trials

Clinical trials of new anticancer therapies form an important part of the research activity of the Cancer Research Campaign (United Kingdom), and quality-of-life (QOL) end points are being increasingly used in the evaluation of new treatment approaches. The Campaign has a unique policy of supporting a broad range of scientific and clinical research, including psychosocial studies, and thus QOL research is generated in a variety of clinical settings. The focus of interest for the Cancer Research Campaign lies in QOL design and assessment rather than the routine application of QOL protocols. Clinical investigators are free to adopt in individual approach, but the Campaign operates a strict peer-review system in protocol assessment. Some standardization of approach is being achieved through consensus of opinion and wide collaboration, both nationally and internationally.     

The importance of sputum cytology in the diagnosis of lung cancer: a cost-effectiveness analysis

STUDY OBJECTIVE: To assess the potential health and cost effects of initial testing with sputum cytology to diagnose lung cancer. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Surveillance Epidemiology and End Results (SEER) program; cost data from Northern California Kaiser Permanente Hospitals and Universities of Stanford and Iowa; National Center for Health Statistics; and a MEDLINE search. INTERVENTIONS: The use of sputum cytologies preceding other tests (ie, fine-needle aspiration, bronchoscopy, thoracoscopy) in patients with suspected lung cancer. MAIN OUTCOME MEASURES: Mortality associated with testing and initial surgical treatment (eg, performance of thoracoscopy to remove a local-stage, centrally located cancer), cost of testing and initial treatment, life expectancy, lifetime cost of medical care, and cost-effectiveness. RESULTS: In central lesions, sputum cytology as the first test was the dominant strategy because it both lowers medical-care costs ($2,516 per patient) and lowers the mortality risk (19 deaths in 100,000 patients) of the evaluation without adversely affecting long-term survival. In peripheral lesions, sputum cytology costs less then $25,000 per year of life saved if the pretest probability of cancer exceeds 50%. The estimated annual savings of adopting sputum cytology as the first test for diagnosing lung cancer in the United States is at least $30 million. CONCLUSIONS: Experience in regional centers indicates that sputum cytologic testing is infrequently ordered before implementing invasive diagnostic techniques, even in patients with central lung masses. The study findings suggest that sputum cytology as the first test in suspected lung cancer is likely to be cost saving without adversely affecting patient outcomes.     

Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison with mammographic surveillance for breast cancer

OBJECTIVE: Endoscopic surveillance of Barrett's esophagus is commonly practiced to detect malignancy in an early and curable stage. However, the cost-effectiveness of this practice has been questioned. To clarify this issue, we undertook a cost analysis of endoscopic surveillance to detect adenocarcinoma in Barrett's esophagus compared with mammography used to detect occult carcinoma of the breast, a widely accepted cancer surveillance technique. METHODS: The rate of esophageal adenocarcinoma detected by endoscopic surveillance was calculated for Duluth Clinic patients with Barrett's esophagus seen from 1980 to 1995 and compared with published rates. The rate of occult breast cancer detection was calculated for all women undergoing surveillance mammography at the Duluth Clinic for the year 1994 and compared with published rates. Costs for screening studies and therapy for cancer treatment for both cancers were calculated based on clinical results and assumptions regarding outcomes derived from published reports, and the costs were compared. RESULTS: Endoscopic surveillance of 149 patients with benign Barrett's esophagus was performed for a total of 510 patient-yr, during which time seven patients developed adenocarcinoma, an incidence of one case per 73 patient-yr of follow-up. Occult breast cancer was detected in 50 of 12,537 mammograms, a detection rate of 0.4%. The incidences in both cases were comparable to published figures. The costs of detecting a case of adenocarcinoma in Barrett's esophagus and occult breast cancer were $37,928 and $54,513, respectively, and those for treatment resulting in cure were $83,340 and $83,292. Cost per life-yr saved was $4,151 for adenocarcinoma in Barrett's esophagus and $57,926 for breast cancer. CONCLUSION: Endoscopic surveillance of patients with Barrett's esophagus compares favorably with the common practice of surveillance mammography to detect early breast cancer, and should therefore be considered to be as cost-effective as surveillance mammography.     

US-guided core breast biopsy: use and cost-effectiveness

OBJECTIVES: We sought to determine, using serial echocardiography, the hydrodynamic mechanisms involved in the occurrence of hemolysis after mitral valve repair. BACKGROUND: Recently, fluid dynamic simulation models have identified distinct patterns of mitral regurgitant flow disturbances in patients with mitral prosthetic hemolysis that were associated with high shear stress and may therefore produce clinical hemolysis. Rapid acceleration, fragmentation, and collision jets were associated with high shear stress and hemolysis whereas slow deceleration and free jets were not. METHODS: We reviewed serial echocardiographic studies of 13 consecutive patients with hemolytic anemia after mitral valve repair who were referred for mitral reoperation between January 1985 and December 1996 (group 1). Thirteen patients undergoing reoperation for mitral regurgitation after mitral valve repair but without hemolysis served as controls (group 2). RESULTS: The mitral regurgitant jet was central in origin in 12 group 1 patients and 9 group 2 patients (Fisher exact test, p= 0.3). The other patients had para-ring regurgitation. Group 1 patients had collision (n=11), rapid acceleration (n=2) or fragmentation (n=1) jets whereas group 2 patients had slow deceleration (n=11) or free jets (n=2) (Fisher exact test, p < 0.0001). One patient with hemolysis had both collision and rapid acceleration jets. The "culprit" jet could be identified on the postbypass transesophageal echocardiography (TEE) study in only 1 patient at the time of initial mitral repair. Twelve group 1 patients underwent reoperation, with subsequent resolution of hemolysis in all patients. At reoperation, the initial repair was found to be intact in 8 (67%) patients. CONCLUSION: Distinct patterns of flow disturbance associated with high shear stress were identified by color Doppler imaging in patients with hemolysis after mitral valve repair. The majority (92%) of these color flow disturbances were not present during intraoperative postbypass TEE study after initial mitral repair and subsequently developed in the early postoperative period.     

Community-based leg ulcer clinics: organisation and cost-effectiveness

To establish the cost effectiveness of community leg ulcer clinics using four-layer compression bandaging and the care provided by district nurses, a randomised controlled trial was set up in eight community-based research clinics in four trusts, funded by Trent Regional Health Authority. The main outcomes monitored were the amount of time needed to complete ulcer healing, patient health status, and recurrence. Satisfaction with care, use of services and personal costs were also monitored.     

A cost-effectiveness approach to the Norwegian follow-up programme in colorectal cancer

BACKGROUND: Today, continued periodic follow-up of patients treated for colorectal cancer (CRC) seems often to be routine because of tradition, rather than its demonstrated value. Recently, the Norwegian Gastrointestinal Cancer Group (NGICG) has recommended a standard surveillance programme in this malignancy. In this protocol patients are suggested followed for four years with CEA monitoring, ultrasound of the liver, chest radiograph and colonoscopy at regular intervals. MATERIALS AND METHODS: In this study, the cost-effectiveness of this programme was addressed employing Norwegian cost data and data from the Cancer Registry of Norway. Clinical data from the existing English language literature was used in the analysis. RESULTS: The basic cost of the NGICG recommended programme was 1,232 Pounds per patient. Including extended investigation due to suspected relapse in 45% of cases, the figure raised to 1,943 Pounds per patient. The cost per life year saved was indicated to 9,525 Pounds-16,192 Pounds. The corresponding cost per quality adjusted life year (QALY) was indicated to 11,476 Pounds-19,508 Pounds. CONCLUSION: We conclude the NGICG recommended follow-up programme in CRC cost-effective. Excluding CEA monitoring may improve the cost-effectiveness.     

Modeling the cost-effectiveness of granulocyte colony-stimulating factor use in early-stage breast cancer

PURPOSE: To model the cost-effectiveness (CE) of granulocyte colony-stimulating factor (G-CSF) in early-stage breast cancer when its use is directed to those most in need of the medication. METHODS: A conditional CE model was developed for the use of G-CSF based on a ranking of patient need as determined by patient blood counts during the first cycle of chemotherapy. In the base case, no G-CSF was used. In the alternative case, G-CSF was used in the following manner. If the risk of a neutropenic event (as defined by a predictive model based on nadir absolute neutrophil count [ANC] and hemoglobin decrease in cycle 1) was equal to or exceeded a predetermined critical value "T," then patients would receive G-CSF in cycles 2 through 6 of chemotherapy. If the risk of an event was less than T, patients would not use G-CSF unless an event occurred, at which time G-CSF would be administered with every subsequent cycle. RESULTS: A decision rule (T) that would allow the most needy 50% of early-stage breast cancer patients to receive G-CSF after the first cycle of chemotherapy resulted in a CE ratio of $34,297 dollars per life-year saved (LYS). If only the most needy 10% of patients received G-CSF, then the associated CE ratio was $23,748/LYS; if 90% of patients could receive the medication, the CE ratio would be $76,487/LYS. These estimates were relatively insensitive to inpatient hospital cost estimates (inpatient costs for fever and neutropenia of $3,090 to $7,726 per admission produced dollar per LYS figures of $34,297 to $32,415, respectively). However, the model was sensitive to assumptions about the shape of the relationship between dose reduction and disease-free survival (DFS) at 3 years. CONCLUSION: Providing G-CSF to the neediest 50% of early-stage breast cancer patients (as defined by first-cycle blood counts) starting after the first cycle of chemotherapy is associated with a CE ratio of $34,297/LYS, which is well in the range of CE ratios for treatment of other common medical conditions. Furthermore, conditional CE studies, based on predictive models that incorporate individual patient risk, allow one to define populations for which therapy is, or is not, cost-effective. Limitations of our present understanding of the shape of the chemotherapy dose-response curve, especially at low levels of dose reductions, affect these results. Further work is required to define the shape of the dose-response curve in early-stage breast cancer.     

Laryngeal papillomatosis: immunologic and viral basis for therapy

The distressing nature of laryngeal papillomatosis and lack of clinical progress in its treatment are reviewed. Presently accepted and investigative methods of therapy are reviewed with special attention being given to immune therapy. Support for the concept of a viral etiology is discussed and other etiologic agents considered. Known and possibly significant roles of wart virus antibodies are discussed and the importance of complex interplay between maternal and fetal immune systems explored as a possible explanation for some puzzling aspects of laryngeal papillomatosis. Finally, a proposed experimental design is outlined, the purpose of which is to provide a useful animal model to investigate immune changes in laryngeal papillomatosis, as well as effects of surgical or medical therapy.     

Laryngeal reinnervation: transposition of neuromuscular pedicles

Following Tucker's technique, a muscle-nerve pedicle implantation in the denervated posterior cricoarytenoid muscle was performed in five dogs. Results were evaluated after six months by videolaryngoscopy, evoked muscle action potentials and histomorphometric studies. Partial motion recovery of the reinnervated side was observed endoscopically in three dogs. Histomorphometric evaluation showed evidence of muscle reinnervation in all of the five dogs. However, no muscle action potentials were obtained in the posterior cricoarytenoid muscles after stimulation of the ansa hypoglossi branch. These data suggest that the ansa hypoglossi neuromuscular pedicle does not result in reinnervation, and that reinnervation of the posterior cricoarytenoid muscle may occur via other neuromuscular pathways.     

Evidence-based medicine and cost-effectiveness analysis

Health care has become increasingly expensive and clinicians have come under increased scrutiny to critically appraise the economic impact of medical programs and interventions. To ensure an equitable allocation of scarce resources and the attainment of maximal clinical benefit, it is vital to adhere to certain basic tenets of economic analysis and to understand the basic approach to cost-effectiveness analysis. These principles are applied to critical care medicine and analogies are made to the methodological rigor of evidence-based medicine.     

Methods of cost-effectiveness analysis: areas of consensus and debate

Methods of evaluating socioeconomic relationships have evolved over many years, and a number of specific approaches have been developed. Among the techniques available, cost-effectiveness analysis (CEA) has emerged as the most widely used and accepted method. Yet, despite considerable effort by the analytical community to refine this technique into one more useful for making health policy decisions, much debate and confusion still persist among analysts, readers, and policy-makers concerning methods standards and the overall usefulness of CEA in resource allocation decision making. Thus the purpose of this paper is to summarize, critically examine, and comment on existing recommended methods for socioeconomic evaluation of health care interventions. In particular, we examine an exhaustive set of component methods within the general area of cost-effectiveness and comment on areas of apparent consensus and debate. Our review reveals many areas of agreement and many yet to be resolved. Analysts generally agree on the components of the overall framework for an analysis; basic methodologic principles; the general treatment of costs; the principle of marginal analysis; the need for and general approach to discounting; the use of sensitivity analysis; the extent to which ethical issues can be incorporated; and the importance of choosing appropriate alternatives for comparison. The principal areas in which disagreement still persists are choice of study design, measurement and valuation of health outcomes including conversion of health outcomes to economic values, transformation of efficacy results into effectiveness outcomes, and the empirical measurement of costs.     

Laryngeal melanosis: report of four cases and literature review

Tumors grafted into mice may modify the proliferation of normal cell populations. In this paper, we have studied the evolution of mitotic activity (MA) in duodenal-crypt enterocytes of ES12a hepatocarcinoma-bearing mice; a total of 87 28-day-old female animals of the C3H/S strain were used after standardization for circadian-periodicity analysis. The mice were distributed into two groups: those remaining intact and those receiving tumor grafts. Each group was then divided into six batches (n = 6-10), one of which was sacrificed every 4 h over a period of one day. A dose of colchicine (2 micrograms/g) was administered to each animal 4 h before killing. Samples of duodenum were fixed in 10% (v/v) buffered formalin and processed for assessment of mitotic activity. The number and topographic localization of the colchicine-arrested metaphases were recorded among the entero-cytes within 20 longitudinal sections of the duodenal crypts in each animal. From these data the mitotic indices over the total crypt-cell population as well as within each previously-established zone were determined along with mean +/- SEM for each experimental group. The statistical significance of the differences among the data were analyzed by Student t test. The results show that the presence of ES12a tumor inhibits the mitotic activity of the duodenal-crypt enterocytes and produces an apparent temporal shift in the peak and trough within the circadian curve for this growth parameter.     

The Head and Neck Radiotherapy Questionnaire: a morbidity/quality-of-life instrument for clinical trials of radiation therapy in locally advanced head and neck cancer

PURPOSE: The purpose of this study was to develop and validate an instrument for clinical trials to measure radiation-related acute morbidity and quality of life from the perspective of patients with head and neck cancer (HNC) treated with radiotherapy. METHODS: The Head and Neck Radiotherapy Questionnaire (HNRQ) was developed by a panel of health care workers and patients, was pretested in a pilot study of HNC patients, and was validated in a randomized double-blind trial of concomitant fluorouracil (FUra) infusional therapy (1.2 g/m2 per 24 hours) or saline placebo administered for 72 hours in the first and third weeks of a 6 1/2-week course of radiation therapy. The HNRQ was validated against existing toxicity and performance status indices, all of which were measured weekly for the 6 1/2 weeks of treatment and for 4 weeks posttreatment. RESULTS: There were three a priori constructs: (1) that the HNRQ scores would conform to a shallow U-shaped pattern to reflect declining quality of life (increasing morbidity) during radiation and recovery posttreatment; (2) that the HNRQ would correlate with existing toxicity indices (World Health Organization [WHO] stomatitis, Byfield stomatitis, WHO skin toxicity, Eastern Cooperative Oncology Group [ECOG] and Karnofsky performance status); and (3) that the HNRQ would discriminate between FUra and placebo groups. The HNRQ and its domain scores all showed a change from baseline reflecting increased morbidity during radiation (analysis of variance [ANOVA], P < .00001). The HNRQ correlated well with all other indices (r > or = .60), and domain scores correlated best with other indices that assess the same symptom complex (eg, HNRQ skin domain and WHO skin toxicity index, r = .77). There was a significant difference in HNRQ scores between the FUra and placebo groups during radiation (ANOVA, P = .0007), and all HNRQ domains also discriminated between the treatment groups. CONCLUSION: The HNRQ is a valid measure of acute morbidity due to radiation therapy in patients with locally advanced HNC, and may be useful as an outcome measure for future clinical trials of radiation treatment strategies.     

Laryngeal atresia in the newborn: surgical implications

Congenital atresia of the larynx is a rare, life-threatening anomaly in which early recognition and appropriate perinatal management are essential for survival. Few long-term survivors have been reported in the literature, with most documented cases studied at necropsy. The authors present a case of a full-term male newborn with Smith and Bain Type I laryngeal atresia, who has survived and developed normally during the 10-months since birth. Rapidly progressive cyanosis following umbilical cord occlusion, lack of phonation, and no air movement with respiratory efforts are typically present and should alert the clinician to the possibility of laryngeal atresia. Positive pressure ventilatory assistance may be possible through a patent pharyngoglottic duct or tracheoesophageal fistula until a surgical airway is established. If this is not possible, emergent tracheostomy may be a lifesaving procedure in the first minutes of life.