Taxane acute pain syndrome (TAPS) in patients receiving chemotherapy for breast or prostate cancer: a prospective multi-center study.

BACKGROUND: Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 2-3 days after taxane-based chemotherapy and lasting up to 7 days. In the absence of validated tools, many studies use the presence of both the myalgia and arthralgia components of the Common Terminology Criteria for Adverse Events (CTCAE) to define TAPS. The present study prospectively evaluated the frequency, severity, and impact of TAPS in patients with breast or prostate cancer. PATIENTS AND METHODS: In this prospective, non-randomized study, patients with breast or prostate cancer commencing taxane-based chemotherapy completed the CTCAE (version 4.03), the Functional Assessment of Cancer Therapy-Taxane (FACT-T), and Brief Pain Inventory (BPI) questionnaires at baseline and once between days 5 and 7 of each chemotherapy cycle. RESULTS: From March 2015 to April 1, 2016, 75 patients (breast n = 66, prostate n = 9) were enrolled; 83% received docetaxel and 16% paclitaxel and 1% withdrew. After the first cycle of taxane, TAPS was reported by 25/69 (36.2%) patients; a further 8/69 (18.2%) reporting TAPS after a subsequent chemotherapy treatment. Overall incidence of TAPS was 33/75 (44%). While associated with detrimental scores on FACT-T and BPI as well as increased use of analgesics in 63% (21/33) of patients with TAPS, TAPS did not lead to alterations in chemotherapy dosing. CONCLUSIONS: TAPS is common after taxane-based chemotherapy, and its presence is associated with reduced quality of life and increased analgesic requirements. Prospective patient-reported outcome assessments are crucial to help individualize treatment strategies and improve management of TAPS.

Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies.

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and to develop their potential as susceptibility biomarkers of cachexia.

The BH3-only protein Bad confers breast cancer taxane sensitivity through a nonapoptotic mechanism.

Antimitotic agents such as taxanes (paclitaxel and docetaxel) have greatly advanced the treatment of breast cancer, although variable patient response and drug toxicity are major limitations. Lack of validated predictive markers for taxane responsiveness precludes a priori identification of patients who are most likely to respond to treatment; thus, a subset of patients endure toxic side effects with marginal benefit. Mechanistic insights into taxane therapeutic activity may lead to rational therapeutic improvements. In this paper we report that the proapoptotic BH3-only protein Bad has a major role in taxane-induced cell death in vitro, and clinically is a prognostic indicator for overall survival of breast cancer patients after adjuvant taxane chemotherapy. Unexpectedly, Bad did not induce the mitochondrial apoptotic machinery in response to taxane treatment. Instead, Bad indirectly facilitated cell death by stimulating cellular proliferation. As dividing cells are the targets of taxane therapy, Bad-stimulated proliferation may be a marker of taxane sensitivity. Our studies indicate that quantification of Bad protein levels may have value as a diagnostic tool. They also suggest that cells expressing Bad are more sensitive to taxanes because of their altered cell cycle dynamics and reveal a clinically relevant proliferative role of Bad in breast cancer.

Identifying the best surface topography parameters for detecting idiopathic scoliosis curve progression.

There is no consensus on which surface topography (ST) parameters may be used to detect scoliosis progression. The sensitivity to change of common ST parameters has not yet been compared. The goal of this study was to determine which ST parameters are most sensitive to scoliosis progression in patients with adolescent idiopathic scoliosis (AIS) receiving conservative treatment. Fifty-eight subjects with AIS were included whose Cobb angle had progressed by at least 5 degrees during a 1 year interval. All had had ST scans and frontal radiographs at a 12 month interval at our clinic. Commonly used back-only ST parameters and contributing scores were derived by one evaluator. Standardized response mean (SRM) and 95% confidence intervals (CI) were calculated using the absolute value of the changes between baseline and follow-up to reflect change in deformity, independent of direction. Decompensation, cosmetic score, Deformity in the Axial Plane Index (DAPI), trunk rotation, Hump Sum, and lordosis angle were highly sensitive to scoliosis progression (SRM>0.8). Cosmetic score, Posterior Trunk Symmetry Index (POTSI), and kyphosis angle had significantly poorer SRM values than the Cobb angle. All other ST parameters had SRM estimates that did not differ significantly from the Cobb angle, suggesting that they have a similar ability to detect progression The ST measures that were most sensitive to detection of scoliosis progression in the frontal, transverse, and sagittal planes were decompensation, trunk rotation, and lordosis angle, respectively. Absolute changes in surface parameters representing either worsening or improvement externally could reflect worsening of the internal deformity. The majority of ST parameters are potentially sensitive to scoliosis progression.

Intrinsic uniformity and relative sensitivity quality control tests for single-head gamma cameras.

OBJECTIVE: We sought to determine the best parameters for rapid performance of daily quality control testing of intrinsic uniformity and relative sensitivity for the single-head gamma-camera system in our nuclear medicine department. METHODS: The effects of the following parameters on intrinsic uniformity were studied: gamma source activity, number of acquired counts for the flood image, source-to-camera distance, image matrix size, and source volume. The dead time of the system was determined experimentally using the two-source method for accurate calculation of relative sensitivity. RESULTS: A set of parameters for rapid performance of daily gamma-camera intrinsic uniformity and relative sensitivity was determined. The dead time of our gamma-camera system was found to be 4.5 +/- 0.2 micros. CONCLUSION: With our recommended parameters, the intrinsic uniformity and relative sensitivity quality control testing can be performed in 5-6 min. The dead time of each gamma-camera system must be determined experimentally in each nuclear medicine department.

Successful Wallstent implantation for extensive iatrogenic renal artery dissection in a patient with fibromuscular dysplasia.

PURPOSE: To describe a case of renal artery stenosis with fibromuscular dysplasia (FMD) and extensive iatrogenic dissection treated with Wallstent implantation. METHODS AND RESULTS: An 83-year-old woman with a history of coronary artery disease and hypertension presented at another facility with exertional angina and poorly controlled hypertension. Renal arteriography uncovered a critical right renal artery stenosis with severe FMD. However, angioplasty resulted in extensive dissection of the renal artery, for which the patient was referred to our institution. The renal artery was recanalized via the left brachial approach with restoration of flow using a Wallstent and a Palmaz stent. The patient's blood pressure was controllable after this procedure, and follow-up duplex imaging with flow velocities at 6 months showed patent right renal artery stents. CONCLUSIONS: Owing to its length and flexibility, the Wallstent endoprosthesis was a useful treatment modality in this case of extensive renal artery dissection.

Benign tumours of the pineal region: a prospective study from 1983 to 1997.

Tumours of the pineal region are rare. Between 1983 and 1997, 128 patients with pineal masses were treated in our institution. Forty-eight (38%) of these were benign. There were 13 patients with meningiomas, 11 with epidermoid tumours, 10 with cystic lesions, five with vascular lesions, five with infective pathology and four with mature teratomas. All patients were managed surgically. Ventriculo-peritoneal shunts were inserted preoperatively to relieve hydrocephalus. Open surgery thereafter was mostly done through the supracerebellar infratentorial approach. The occipital transtentorial route was preferred for meningiomas. Stereotactic biopsy was used in two patients only. Radical excision of tumours was achieved in 55% of operated cases, partial excision in 25%. Radiation therapy, which was the mainstay of treatment earlier, was used only in two patients. Stereotactic radiosurgery was used in one patient. All patients followed up were found to be in good or excellent condition.

Validation study of a central venous pressure-based protocol for the management of neurosurgical patients with hyponatremia and natriuresis.

OBJECTIVE: We had previously suggested a protocol for the management of neurosurgical patients with hyponatremia and natriuresis that was based on their volume status as determined by actual blood volume measurements. All patients in that study were found to be hypovolemic or normovolemic and responded, within 72 hours, to salt and fluid replacement. In the present study, the validity of that protocol was tested using central venous pressure as the sole measure of volume status of patients with hyponatremia and natriuresis. METHOD: Twenty-five consecutive patients (26 cases) who fulfilled the inclusion criteria typically used to diagnose the syndrome of inappropriate secretion of antidiuretic hormone were included in the study. Central venous pressure was used to classify patients as hypovolemic (< 5 cm of water), normovolemic (6-10 cm of water), or hypervolemic (> 11 cm of water). Hypovolemic patients were given fluids (50 ml/kg/d) and salt (12 g/d). Normovolemic patients were given normal fluid with 12 g of salt per day. In addition, patients with anemia (hematocrit, < 27%) were administered whole blood. The end point was a serum sodium of more than or equal to 130 mEq/L measured in two consecutive samples 12 hours apart or 72 hours after entry into the study. If the serum sodium was less than 130 mEq/L at the end of 72 hours, the clinical condition of the patient determined further management. RESULTS: Nineteen of 25 patients (26 cases) were hypovolemic, the rest were normovolemic. No patient was hypervolemic. Nineteen of 25 patients (26 cases) attained normal serum sodium values within 72 hours, and an additional 3 responded within the next 36 hours (108 h after entry into the study). One patient who was discharged on request had normalized her serum sodium a week later. Among the three nonresponders, who were severely hypovolemic, as revealed by blood volume measurement, and responded to increased fluid and salt administration. One was normovolemic and responded to increased salt administration. There were no complications related to the therapy. CONCLUSION: Hyponatremia with natriuresis in the neurosurgical setting responds to salt and fluid replacement guided by the patients' volume status as determined by the central venous pressure. This study also offers further indirect evidence to suggest that the syndrome of hyponatremia with natriuresis is most often caused by "cerebral salt wasting" rather than by the syndrome of inappropriate secretion of antidiuretic hormone.

Predictors of primary patency failure in Wallstent self-expanding endovascular prostheses for iliofemoral occlusive disease.

We studied the factors that affected the primary patency and the clinical and procedural success of WALLSTENTS (stents) that were used at our institution from 1 March 1994 to 30 October 1995 for the treatment of iliac and femoral artery occlusive disease. This prospective study comprised 63 patients with 82 lesions. Follow-up was performed for a mean duration of 18.7 months. Pre- and post-procedural duplex ultrasonography, together with estimation of ankle-brachial index scores, was performed on all patients, and additional studies were performed at clinical follow-up if indicated. The technical success rate was 100%. Ankle-brachial index scores improved considerably from 0.52 +/- 0.21 before the procedure to 0.73 +/- 0.27 after the procedure. The significant predictors by univariate analysis of primary patency failure were: Fontaine class III or IV (P = 0.044); femoral location (P = 0.004); lesion length > 100 mm (P = 0.010); poor or moderate outflow (P = 0.026); and number of stents > or = 3 (P = 0.012). Cox regression analysis showed that > or = 3 stents (risk ratio = 5.61), poor or moderate outflow (risk ratio = 6.05), and femoral location (risk ratio = 5.18) were the significant predictors of primary patency failure. Femoral lesions required more stents than did iliac lesions (2.2 +/- 0.8 vs 1.3 +/- 0.5). Primary patency rates for iliac and femoral stents were 86% and 49%, respectively, at 12 months, and 82% and 41% at 24 months.

Angiotensin-I converting enzyme genotype DD is a risk factor for coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a polygenic disease whose phenotypic manifestation is due to interaction of a number of environmental factors with an underlying genetic background. A number of genes, including the angiotensin-I converting enzyme (ACE) gene, have been implicated in the pathogenesis of CAD. ACE can affect oxidation of LDL, endothelial cell function, and smooth muscle cell migration and proliferation: all important components of atherosclerosis. A variant of ACE gene, genotype DD is associated with a higher plasma level of ACE and an increased risk of myocardial infarction, and cardiomyopathies. In this study, we sought to determine the distribution of ACE genotypes and the frequency of allele D in patients with CAD undergoing coronary angioplasty. METHODS: DNA from 182 white patients undergoing coronary angioplasty and 338 apparently healthy white individuals was amplified by polymerase chain reaction (PCR) in the region of the polymorphism using the previously published protocol. RESULTS: PCR amplification of alleles I and D resulted in 490 bp and 190 bp products, respectively. ACE genotype DD was present in 47% of patients with CAD as compared to 30% in the general population (p = 0.0002, Odds ratio 2.7). The frequency of allele D was 0.68 in patients with CAD and 0.55 in general population, respectively (p < 0.0001). Genotype DD was associated with CAD only in males (54% vs. 30%, p = 0.0001, Odds ratio 2.0), but not in female patients. There was no association between the frequency of ACE genotype DD and the prior history of myocardial infarction, or the extent of CAD. The frequency of ACE genotype DD was the highest among patients with restenosis following angioplasty (55%), however, the difference was not significantly changed as compared to those without restenosis (40%). CONCLUSIONS: ACE genotype DD is more common in patients with CAD as compared to the general population, indicating that genotype DD is a genetic risk factor for CAD.