Quality of life following breast-conserving therapy or mastectomy: results of a 5-year prospective study.

There are many conflicting results in the literature comparing quality of life following breast-conserving therapy (BCT) and mastectomy. This study compared long-term quality of life between breast cancer patients treated by BCT or mastectomy in three age groups. Patients (n = 990) completed a quality of life survey, including the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), at regular intervals over 5 years. In the cross-sectional data, mastectomy patients had significantly (p < 0.01) lower body image, role, and sexual functioning scores and their lives were more disrupted than BCT patients. Emotional and social functioning and financial and future health worries were significantly (p < 0.01) worse for younger patients. There were no differences in body image and lifestyle scores between age groups. There was also no interaction between age and surgery method. Even patients > or =70 years of age reported higher body image and lifestyle scores when treated with BCT. The repeated measures analysis indicated that four functioning scores, half the symptom scores, future health, and global quality of life improved significantly (p < 0.01) over time. All these variables increased significantly for BCT patients and those 50 to 69 years of age. Body image, sexual functioning, and lifestyle disruption scores did not improve over time. BCT should be encouraged in all age groups. Coping with appearance change should be addressed in patient interventions.

Predictors of quality of life of breast cancer patients.

Research has indicated that several demographic and clinical factors may affect the quality of life of breast cancer patients. Few studies, however, have sufficient sample sizes for multivariate analyses to be tested. Furthermore, several important factors, such as arm morbidity, communication and comorbid illness, have not been included in quality of life models The aim of this study was to predict the simultaneous effect of these factors on long-term quality of life. Breast cancer patients (n = 990) completed a quality of life survey, including the EORTC QLQ-C30, over five years. Clinical details were registered in the Munich Cancer Registry. Eleven predictors across eight quality of life domains were analyzed over a period of five years using a logistic regression model. Arm problems, communication, comorbidity, age, surgery. and, to a lesser extent, marital, educational and employment status were significantly associated with quality of life. Adjuvant therapy, medical insurance and pT category were not significant predictors. This study is the first to demonstrate the consistency and strength of arm dysfunction and doctor-patient communication on breast cancer patients' quality of life. These important factors in breast cancer care can be improved and should be regarded as a priority.

Synthesis, molecular modeling and biological evaluation of aza-proline and aza-pipecolic derivatives as FKBP12 ligands and their in vivo neuroprotective effects.

Nonimmunosuppressant ligands, exemplified by GPI 1046 (1), for the peptidyl-prolyl isomerase FKBP12 have been found to unexpectedly possess powerful neuroprotective and neuroregenerative effects in vitro and in vivo. We have extensively explored the therapeutic utility of FKBP12 ligands based on analogues of proline and pipecolic acid. As part of our ongoing program to explore novel structural classes of FKBP12 ligands, we herein wish to report a new class of FKBP12 ligands containing aza-proline and aza-pipecolic acid analogues. Details of the synthetic studies, together with biological activity will be presented.

Quality of life in rectal cancer patients: a four-year prospective study.

OBJECTIVE: To assess long-term quality of life in a population-based sample of rectal cancer patients. SUMMARY BACKGROUND DATA: Quality of life in rectal cancer patients who suffer reduced bowel and sexual function is very important. Few studies, however, have long term follow-up data or sufficient sample sizes for reliable comparisons between operation groups. PATIENTS AND METHODS: A 4-year prospective study of rectal cancer patients' quality of life was assessed by using the European Organization for Research and Treatment of Cancer QLQ-30 and CR38 questionnaires. RESULTS: A total of 329 patients returned questionnaires. Overall, anterior resection patients had better quality of life scores than abdominoperineal extirpation patients. High-anterior resection patients had significantly better scores than both low-anterior resection and abdominoperineal extirpation patients. Low-anterior resection patients, however, overall had a better quality of life than abdominoperineal extirpation patients, especially after 4 years. Abdominoperineal extirpation patients' quality of life scores did not improve over time. Stoma patients had significantly worse quality of life scores than nonstoma patients. Quality of life improved greatly for patients whose stoma was reversed. CONCLUSIONS: Anterior resection and nonstoma patients, despite suffering micturition and defecation problems, had better quality of life scores than abdominoperineal extirpation and stoma patients. Comparisons between abdominoperineal extirpation and anterior resection patients should consider the effect of temporary stomas. Improvements in quality of life scores over time may be explained by reversal of temporary stomas or physiologic adaptation.

Doctor-patient communication: results of a four-year prospective study in rectal cancer patients.

PURPOSE: The purpose of the study was to examine the effect of communication on rectal cancer patients' quality of life over four years. Previous studies have either used short follow-up periods or examined only certain aspects of quality of life, such as anxiety and depression. METHODS: In a prospective, observational study, rectal cancer patients, recruited by clinicians over a two-year period, were sent questionnaires over four years. The clinical details of these patients were recorded by the Munich Cancer Registry. The psychological scores from the European Organization for Research and Treatment of Cancer QLQ-C30 and CR38 were the main outcome variables. RESULTS: Thirty-nine percent of the sample reported that some aspect of the communication they received was unclear (incomprehensible or too little). More than 60 percent wished to speak more with their physician. Younger patients and those in larger hospitals were more likely to report unclear communication (P < 0.05). Analyses of covariance, controlled for age, gender, adjuvant therapy, stoma, education, clinic, and comorbidity, demonstrated that role, emotional, and social functioning scores were consistently lower in patients reporting unclear communication. Additionally, these patients experienced more problems sleeping, poorer body image, more financial worries, and a worse future perspective. Repeated measures analyses indicated that sleeping problems and emotional and social functioning difficulties persisted for at least three years. CONCLUSION: Reports of unclear communication were associated with poorer quality of life in rectal cancer patients without disease progression.

Axilla surgery severely affects quality of life: results of a 5-year prospective study in breast cancer patients.

No long-term prospective study has investigated arm morbidity and patient quality of life. It is unclear to what extent breast cancer patients suffer from arm problems, how long such problems affect their lives, and whether quality of life improves as arm problems abate. This prospective cohort study aims to provide data on the clinical factors associated with arm dysfunction, to estimate its prevalence and to relate arm morbidity to quality of life. The Munich Cancer Registry records clinical details of all cancer patients in and around Munich. Quality of life information was provided directly by breast cancer patients (n = 990) over 5 years. Arm morbidity, including movement limitations, swelling and lymph drainage, and quality of life (EORTC QLQ-C30) were assessed. Up to 5 years after diagnosis, 38% of patients were still experiencing arm problems (swelling and limited movement). Consistently over the 5 years, quality of life was significantly (p < 0.001) lower for patients with arm difficulties. For those whose arm problems dissipated, quality of life significantly improved (p < 0.01). A logistic regression analysis showed that extent of axilla surgery (p < 0.003), comorbidity (CVD and diabetes) (p < 0.003), employment (p < 0.01), younger age (p < 0.02), and operating clinic (p < 0.05) significantly contributed to arm problems. Axilla surgery should be re-evaluated since arm morbidity has such a profound effect on patient quality of life.

Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects.

The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands.

Synthesis of ketone analogues of prolyl and pipecolyl ester FKBP12 ligands.

The recently discovered small-molecule ligands for the peptidyl and prolyl isomerases (PPIase) of FKBP12 have been shown to possess powerful neuroprotective and neuroregenerative effects. Ketone analogues of the prolyl and pipecolyl esters, which mimic only the FKBP binding domain portion of FK506, are proposed and an efficient synthetic strategy is presented in this report, along with the preliminary results of in vitro and in vivo biological studies.