The systemic treatment of recurrent ovarian cancer revisited.

Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.

Procoagulant activity in gynaecological cancer patients; the effect of surgery and chemotherapy.

BACKGROUND: Gynaecological cancers are associated with high rates of venous thromboembolism (VTE). Studies on ambulatory cancer patients do not support thromboprophylaxis during chemotherapy. Approximately 6-7% of gynaecological cancer patients suffer a postoperative VTE despite Low Molecular Weight Heparin prophylaxis (LMWH). Large cancer studies have shown that Calibrated Automated Thrombogram (CAT) and Microparticles (MP) assays may be useful in predicting VTE but data on gynaecological cancer patients is scarce. OBJECTIVE: Our objective was to identify whether the CAT assay and MP functional assays have potential as biomarkers predictive of VTE in gynaecological cancer patients. PATIENTS AND METHODS: Gynaecological cancer patients were investigated before surgery (n=146) and at 5, 14 and 42days post-surgery (n=78). Fourteen additional patients were investigated before chemotherapy and after 3 and 6 cycles of therapy. Thrombin generation was measured before and after addition of thrombomodulin. RESULTS: Patients with clear cell cancer (CCC) of the ovary and patients with endometrial cancer had higher ETP and peak thrombin compared with patients with benign disease. Patients who developed VTE (n=8) following surgery had enhanced thrombin generation prior to surgery which persisted during the post-operative period despite LMWH prophylaxis. Both neoadjuvant and adjuvant chemotherapy showed increased thrombin generation following addition of thrombomodulin. There were no differences in MP levels during the study. CONCLUSIONS: CAT assay shows potential as a promising biomarker for the prediction of VTE in gynaecological cancer patients. The identification of high risk patients combined with individualised LMWH prophylaxis might reduce VTE in this high risk group.

Calculating the costs of an 8-week, physiotherapy-led exercise intervention in deconditioned cancer survivors in the early survivorship period (the PEACH trial).

Strong evidence exists for rehabilitation programmes following a cancer diagnosis, although little is known about their cost. The effects of an 8-week, physiotherapy-led, structured group intervention during the early survivorship phase were evaluated. Significant changes in quality of life and fatigue, and promising changes in fitness were found. The overall cost for this programme was €196 per participant, including the salaries of the clinicians, overheads and equipment costs. The modest costs associated with this programme may support more routine 'cancer rehabilitation', although more robust analyses are required.

A guide to assessing physical activity using accelerometry in cancer patients.

Increased physical activity (PA) has been associated with a decreased risk for the occurrence and recurrence of many cancers. PA is an important outcome measure in rehabilitation interventions within cancer and may be used as a proxy measure of recovery or deterioration in health status following treatment and in the palliative care setting. PA is a complex multi-dimensional construct which is challenging to measure accurately. Factors such as technical precision and feasibility influence the choice of PA measurement tool. Laboratory-based methods are precise and mainly used for validation purposes, but their clinical applicability is limited. Self-report methods such as questionnaires are widely used due to their simplicity and reasonable cost; however, accuracy can be questionable. Objective methods such as pedometers measure step count but do not measure intensity, frequency or duration of activity. Accelerometers can measure PA behaviour at both ends of the movement spectrum from sedentary to vigorous levels of activity and can also provide objective data about the frequency, intensity, type and duration of PA. Balancing precision with ease of use, accelerometry may be the best measure of PA in cancer-based studies, but only a small number of studies have incorporated this measurement. This review will provide a background to PA and an overview of accelerometer measurement as well as technical and practical considerations, so this useful tool could be more widely incorporated into clinical trial research within cancer.

Testing the 'teachable moment' premise: does physical activity increase in the early survivorship phase?

PURPOSE: Little is known about objectively measured physical activity during the early survivorship period. This study measured physical activity, fatigue, and quality of life (QOL) in breast cancer patients over the first year after completion of chemotherapy and compared results to a matched non-cancer group. METHODS: Data was obtained from 24 breast cancer subjects (mean ± SD) 50.9 ± 12.8 years at time points of 6 weeks, 6 months and 1 year after completion of adjuvant chemotherapy and from 20 matched women. The following variables were assessed, physical activity (RT3 accelerometer and International Physical Activity Questionnaire), quality-of-life (EORTC QLQ C-30) and fatigue (Brief Fatigue Inventory). RESULTS: At 6 weeks after completion of chemotherapy, high levels of sedentary behaviour were found (6.8 ± 1.9 h sedentary per day), which did not improve, and was no different to the comparison group (6.5 ± 1.4 h). Less light activity was performed in the cancer cohort compared to the comparison group (p = 0.003). Body mass index (BMI) increased significantly in the cancer cohort (p = 0.015) and 1 year after chemotherapy finished only 13% (n = 3) had a BMI <25, while the comparable value was 45% (n = 9) in the non-cancer group. The QOL domain of cognitive function improved over the first 6 months (p = 0.034) but physical functioning declined (p = 0.008) over this time period. Fatigue did not change, and at the 1-year time point, 38% of the cancer patients (n = 11) reported high levels of fatigue. CONCLUSION: This study highlighted the unchanging sedentary behaviour and weight gain of breast cancer survivors during the first year after completion of chemotherapy, which may inform rehabilitation models in this population.

Feasibility and efficacy of a supervised exercise intervention in de-conditioned cancer survivors during the early survivorship phase: the PEACH trial.

PURPOSE: This study aims to evaluate the feasibility and efficacy of an 8-week supervised exercise program in de-conditioned cancer survivors within 2-6 months of chemotherapy completion. METHODS: Participants were randomly assigned to an 8-week, twice-weekly, supervised aerobic exercise training regime (n = 23) or a usual care group (n = 20). Feasibility was assessed by recruitment rate, program adherence and participant feedback. The primary outcome was aerobic fitness assessed by the Modified Bruce fitness test at baseline (0 weeks), post-intervention (8 weeks) and at 3-month follow-up. Secondary outcomes included physical activity, waist circumference, fatigue and quality of life. RESULTS: The recruitment rate was 81 % and adherence to the supervised exercise was 78.3 %. Meaningful differences in aerobic fitness between the exercise and usual care groups at both the 8-week [mean 3.0 mL kg(-1) min(-1) (95 % CI -1.1-7.0)] and 3-month follow-up [2.1 mL kg(-1) min(-1) (-2.3-6.6)] were found, although these differences did not achieve statistical significance (p values >0.14). Self-reported physical activity increased in the exercise group (EG) compared to the usual care group at both 8-week (p = 0.01) and 3-month follow-up (p = 0.03) and significant differences in favour of the EG were found for physical well-being at both the 8-week (p = 0.03) and 3-month follow-up (p = 0.04). Improvements in fatigue (p = 0.01), total quality of life plus fatigue (p = 0.04), and a composite physical functioning score (p = 0.01) at the 3-month follow-up were also found. CONCLUSION: The PEACH trial suggests that 8 weeks of supervised aerobic exercise training was feasible and may improve aerobic fitness, fatigue and quality of life in de-conditioned cancer survivors during the early survivorship phase. IMPLICATIONS FOR CANCER SURVIVORS: Exercise interventions commenced in the early survivorship phase appear safe, feasible and may lead to improvements in QOL and fatigue.

Pulmonary complications in neuromuscular disease.

Pulmonary compromise can result from primarily peripheral or central neuropathic disease (including neurodegenerative diseases) or diseases of the muscle or neuromuscular junction. Some diseases present with a combination of nervous system and muscle tissue involvement (due to secondary changes like atrophy or primary pathology, as in mitochondrial diseases). While clinically different in pathophysiology, these diseases may progress to produce and ìshareî common pulmonary pathology by the time the patient reaches the adolescent years. This article presents a review of the categories of neurologic disease that may lead to respiratory compromise, followed by thorough description of the pulmonary complications that can result from these types of diseases. Finally, a review of currently accepted treatment options that may aid in improving the quality of life of these patients is offered.

Effect of pulmonary edema on tracheal diameter.

BACKGROUND: Though it is well known that cardiogenic and noncardiogenic pulmonary edema can cause changes in lung mechanics, actual alterations in tracheal diameter have not been described. OBJECTIVE: To evaluate the effects of pulmonary edema induced by increased left atrial pressure (cardiogenic) and Perilla ketone (PK; noncardiogenic) on tracheal diameter in chronically instrumented awake sheep. METHODS: We investigated the effects of two mechanistically distinct types of pulmonary edema on tracheal diameter in chronically instrumented awake sheep. Cardiogenic pulmonary edema (analogous to congestive heart failure in humans) was induced by increasing left atrial pressure ( upward arrowP(LA)) by inflating the balloon on a Foley catheter positioned in the mitral valve annulus to cause partial obstruction to flow across the valve (n = 18). Noncardiogenic pulmonary edema (increased pulmonary microvascular permeability pulmonary edema analogous to the acute respiratory distress syndrome in humans) was produced by the intravenous administration of PK (n = 11). Lateral chest radiographs (CXRs) were scored by a standardized 5-point scoring system for the severity of pulmonary edema, and tracheal diameter was measured at a fixed location in the carina. Three radiologists, blinded to sheep identification number and experimental protocol, evaluated the radiographs independently at different points in time for edema severity and tracheal diameter. The sheep were sacrificed immediately after the final CXR, and wet/dry lung weight ratio (W/D ratio) was determined. RESULTS: Both upward arrowP(LA) and PK were associated with statistically significant tracheal narrowing ( upward arrowP(LA): 20.3 +/- 0.6 to 15.1 +/- 0.9 mm; PK: 20.2 +/- 0.6 to 14.1 +/- 1.4 mm). Tracheal narrowing correlated with the severity of the pulmonary edema determined radiographically ( upward arrowP(LA): r = -0.69, p < 0.01; PK: r = -0.62, p < 0.01) and by W/D ratio ( upward arrowP(LA): r = -0.64, p < 0.05; PK: r = -0.54, p < 0. 05). CONCLUSIONS: We conclude that tracheal narrowing occurs in sheep models of both cardiogenic and noncardiogenic pulmonary edema and that the degree of narrowing correlates with the severity of the edema.

The significance of excessive rhythmic alpha and/or theta frequency activity in the EEG of the neonate.

OBJECTIVE: The goal of this study was to determine the significance of excessive rhythmic alpha and/or theta frequency activity in neonatal EEGs. METHODS: The EEGs of 963 neonates, 26-44 weeks conceptional age (CA), performed during the years 1992-1994 at the Texas Children's Hospital, Houston, Texas, were reviewed for the presence of excessive rhythmic alpha and/or theta frequency activity. Cases in which such activity was identified were further characterized by the presence or absence of other EEG abnormalities. The medical records of these patients and a group of control infants with normal EEGs were reviewed to identify associated pathological conditions. RESULTS: Forty patients were identified whose EEGs revealed such activity. The CA of these patients ranged from 37 to 44 weeks. A variety of pathological conditions were seen in these patients, most commonly congenital heart disease, congenital brain anomalies and hypoxia. These conditions were not seen in the control group of infants. Twenty patients had received CNS-active drugs. The EEGs of 32 patients revealed additional abnormalities, most commonly multifocal sharp waves and episodes of voltage attenuation during slow-wave sleep. CONCLUSIONS: The results indicate that excessive rhythmic alpha and/or theta frequency activity is an abnormal finding in the newborn's EEG.

Enuresis: current concepts.

Incontinence disorders are an important group of problems that clinicians manage in children and adolescents. This paper reviews the physiology of micturition, the epidemiology of enuresis, etiologic concepts of incontinence disorders, a general clinical approach to enuretic patients, laboratory evaluation and general principles of management. Neurological and nephrological concepts of enuresis are emphasized in this discussion.

Exhaled nitric oxide and bronchoalveolar lavage nitrite/nitrate in active pulmonary sarcoidosis.

Increased exhaled nitric oxide (NO) may reflect respiratory tract inflammation in untreated asthmatics. We compared exhaled NO and bronchoalveolar lavage (BAL) nitrate/nitrite (NO3-/NO2-) in 10 patients who had untreated, active pulmonary sarcoidosis with those of normal control subjects. Exhaled NO concentrations, determined by chemiluminescence, were similar in patients and control subjects (peak NO concentration of patients [mean +/- SD]: 13.6 +/- 5.9 parts per billion [ppb], peak NO concentration of control subjects: 11.2 +/- 5.7 ppb, p = 0.32; mean alveolar NO concentration of patients: 7.8 +/- 4.4 ppb, mean alveolar NO concentration of control subjects: 7.1 +/- 4.2 ppb, p = 0.70; end-tidal NO concentration of patients: 6.9 +/- 4.5 ppb, end-tidal NO concentration of control subjects: 6.6 +/- 4.0 ppb, p = 0.60). BAL NO2- was assayed using a modified Griess reaction after reduction of NO3- to NO2-. There was no significant difference in mean BAL NO2- concentrations, expressed as nanomoles per milliliter of epithelial lining fluid (patients: 544 nmol/ml, control subjects: 579 nmol/ml, p = 0.81) or as nanomoles per milliliter of BAL fluid (patients: 6.7 nmol/ml, control subjects: 5.7 nmol/ml, p = 0.41). These data suggest that excess NO generation does not accompany the respiratory tract inflammation of pulmonary sarcoidosis.

Trinucleotide repeat disorders in pediatrics.

The relationship between the expansion of trinucleotide repeat sequences and human disease hs been the subject of a significant volume of study since the identification of a CGG repeat sequence in the mutated gene responsible for the fragile X syndrome. Six other neurologic diseases are now known to result from a triplet repeat expansion of either CTG or CAG nucleotides. Of particular interest to the pediatrician or pediatric subspecialist is the phenomenon of "anticipation," now clarified by mechanisms inherent to trinucleotide repeat expansions. The progressive enlargement of repeat sequences in successive generations of affected kindreds correlates inversely with the age of onset and, in some cases, the severity of the disease. The presentation of a young patient with symptoms ranging from developmental delay to movement disorders and ataxia requires that the physician involved in the child's care be aware of these diseases, their phenotypic variability, and their effects in previous generations. In this manner, pertinent history, including family history, may be obtained, relevant diagnostic testing initiated, and appropriate referrals facilitated.

Staging lung carcinoma with a Tc-99m labeled monoclonal antibody.

Thirty-three patients with biopsy-proven lung cancer and a total of 150 lesions diagnosed by conventional staging procedures were imaged using a Tc-99m labeled monoclonal Fab fragment of an IgG2B murine monoclonal antibody (MoAb) (NR-LU-10, NeoRx Corporation). Immunoscintigraphy demonstrated 100% of primary and 78% of metastatic lesions. MoAb imaging detected 88% of lesions in 12 small cell lung cancer (SCLC) patients and 77% of lesions in 21 non-small cell lung cancer (NSCLC) patients. Based on initial evaluation by other methods, 29 sites of MoAb activity were not associated with evidence of disease. Eleven of these were subsequently shown to represent sites of metastases; 18 remain unconfirmed. Four of ten patients studied with limited NSCLC had eight unsuspected lesions on MoAb imaging. Confirmation of unsuspected lesions in two patients altered initial clinical staging, and surgical therapy was abandoned. This study demonstrates that Tc-99m labeled NR-LU-10 can accurately stage patients with lung cancer.

Clinical implications of combined hypogastric and profunda femoral artery occlusion.

From 1983 to 1990, nine patients with combined hypogastric (HA) and profunda femoral arterial (PFA) occlusive disease presented with five nonhealing hip disarticulations, three nonhealing above-the-knee amputations, perineal necrosis in six patients, buttock necrosis in four patients, visceral ischemia in two patients, and lumbosacral spinal ischemia in one patient. Obviously some patients had more than one regional complication. Five patients died from complications of HA/PFA ischemia. Survivors included two patients who required a hemipelvectomy, one patient who required an axillary-to-hypogastric artery bypass graft for stump salvage, and one patient who survived despite lumbosacral paralysis and complete cystectomy. The 56% mortality and 100% morbidity emphasize the critical significance of combined hypogastric/profunda femoral artery circulatory compromise. Efforts should be made to preserve or re-establish the HA and/or PFA circulation whenever possible. A hemipelvectomy may be required to allow the wounds to finally heal. Furthermore, the certainty of an above-the-knee amputation healing is not present in these patients; therefore, a hemodynamic assessment of the healing potential of an above-the-knee amputation is required.