Analysis of delay in adjuvant chemotherapy in locally advanced rectal cancer.

BACKGROUND: Adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and surgical resection has been the standard of care for locally advanced rectal cancer. However, there are no evidence-based guidelines regarding the optimal timing of AC for rectal cancer. The objective of this study was to evaluate the effect of AC timing on overall survival for rectal cancer. METHODS: The National Cancer Database (NCDB) from 2004 to 2016 was queried for primary clinical stage II or III rectal cancer patients who had undergone neoadjuvant chemoradiation followed by surgery and AC. Patients were grouped based on AC initiation: early ≤ 4 weeks, intermediate 4-8 weeks, and delayed ≥ 8 weeks. The primary outcome was overall survival. RESULTS: We identified 8722 patients, of which 905 (10.4%) received early AC, 4621 (53.0%) intermediate AC, and 3196 (36.6%) delayed AC. Pathological lymph-node metastasis (ypN +) was positive in 73% of early AC, 74% intermediate AC, and 63% delayed AC (p < 0.05). The 5-year survival probability was 71.1% (95% CI 68-74%) for early AC, 73.2% (95% CI 72-75%) intermediate AC, and 65.8% (95% CI 64-68%) delayed AC (p < 0.001). Using Cox proportional hazard modeling, patients undergoing delayed AC had an associated decreased survival compared to patients receiving early AC (HR 1.18; 95% CI 1.028-1.353, p = 0.018) or intermediate AC (HR 1.28; 95% CI 1.179-1.395, p < 0.01). CONCLUSIONS: Delay in AC administration may be associated with decreased 5-year survival. Compared to early or intermediate AC, patients in the delayed AC group were observed to have increased risk of death, despite having lower proportions with ypN + disease. Patients with higher socioeconomic and education status were more likely to receive early chemotherapy.

Information needs of oncologists, general practitioners and other professionals caring for patients with cancer.

Oncology is a rapidly developing field with a growing number of publications every year. The main goal of this survey was to learn more about the information needs of oncologists and general practitioners. Data were collected using a standardised questionnaire developed in collaboration with the German Cancer Society (Deutsche Krebsgesellschaft) and the German Association of General Practitioners (Deutscher Hausärzteverband). A total of 495 questionnaires could be evaluated. Medical congresses were the preferred source of information for all participants. General practitioners preferred textbooks, while oncologists preferred journals and the Internet (all p < .001). Reasons for a lack of confidence during patient consultation were lack of time (60% of participants), lack of knowledge (61% of general practitioners and 26% of oncologists) and lack of data (>50%). Oncologists felt more confident in searching scientific databases than general practitioners did. Both groups required rapid access to transparent information. For general practitioners, reviews and comments by experts helped to put new information in the context of cancer treatment. Oncologists and general practitioners showed significantly different information needs and different ways to access specific information. In order to better integrate general practitioners while simultaneously serving the needs of oncologists, a database that is up to date, rapidly accessible and does not incur high costs would be helpful.

Application and feasibility of systemic lupus erythematosus reproductive health care quality indicators at a public urban rheumatology clinic.

OBJECTIVES: Quality indicators (QIs) are evidence-based processes of care designed to represent the current standard of care. Reproductive health QIs for the care of patients with systemic lupus erythematosus (SLE) have recently been developed, and examine areas such as pregnancy screening for autoantibodies, treatment of pregnancy-associated antiphospholipid syndrome, and contraceptive counseling. This study was designed to investigate our performance on these QIs and to explore potential gaps in care and demographic predictors of adherence to the QIs in a safety-net hospital. METHODS: We performed a record review of patients with a diagnosis of SLE at Denver Health Medical Center (DH) through an electronic query of existing medical records and via chart review. Data were limited to female patients between the ages of 18 and 50 who were seen between July 2006 and August 2011. RESULTS: A total of 137 female patients between the ages of 18 and 50 were identified by ICD-9 code and confirmed by chart review to have SLE. Of these, 122 patients met the updated 1997 American College of Rheumatology SLE criteria and had intact reproductive systems. Only 15 pregnancies were documented during this five-year period, and adherence to autoantibody screening was 100 percent. We did not have any patients who were pregnant and met criteria for pregnancy-associated antiphospholipid syndrome. Sixty-five patients (53%) received potentially teratogenic medications, and 30 (46%) had documented discussions about these medications' potential risk upon their initiation. Predictors of whether patients received appropriate counseling included younger age (OR 0.92, CI 0.87-0.98) and those who did not describe English as their primary language (OR 0.24, CI 0.07-0.87) in the multivariate analysis. CONCLUSIONS: We were able to detect an important gap in care regarding teratogenic medication education to SLE patients of childbearing potential in our public health academic clinic, as only one in two eligible patients had documented appropriate counseling at the initiation of a teratogenic medication.

Cardiopulmonary correlates of cognition in systemic lupus erythematosus.

OBJECTIVE: We aimed to evaluate the relationship between cognitive dysfunction and lung function, exercise endurance, and self-reported activity levels in patients with systemic lupus erythematosus (SLE). BACKGROUND: Cognitive dysfunction is present in 20%-60% of SLE patients. No studies to date have investigated the inter-relationships between cardiopulmonary factors and cognition in this population. METHODS: Thirty-seven SLE patients without overt neuropsychiatric histories and 16 healthy controls completed neuropsychological testing, measures of lung function, exercise capacity (distance walked during a timed walk test,(1) maximal oxygen uptake(2)), and exercise questionnaires. RESULTS: Thirty-two percent of SLE patients demonstrated cognitive impairment. Cognitive impairment was correlated with Six-Minute Walk Distance (6MWD) (r = 0.37, p = 0.02) and certain measures of lung function. Also, in SLE patients, self-reported physical activity was correlated with 6MWD (p = 0.012), but none of the more complex measures of physical activity (VO2max). CONCLUSIONS: Patients with mild SLE disease activity have cognitive dysfunction associated with certain objective markers of exercise capacity and activity levels. The lack of associations between self-report activity and VO2max suggests the possibility that multiple factors mediate the relationships between perceived and actual physical ability. Additional studies are needed to better understand the relationship between cognition and physical activity in patients with SLE.

Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas.

BACKGROUND: The polyamine-inhibitory regimen difluoromethylornithine (DFMO)+sulindac has marked efficacy in preventing metachronous colorectal adenomas. Polyamines are synthesised endogenously and obtained from dietary sources. Here we investigate dietary polyamine intake and outcomes in the DFMO+sulindac colorectal adenoma prevention trial. METHODS: Dietary polyamine data were available for 188 of 267 patients completing the study. Total dietary polyamine content was derived by the sum of dietary putrescine, spermine and spermidine values and categorised into two groups: highest (>75-100%) vs the lower three quartiles (0-25, 25-50 and 50-75%). Baseline tissue polyamine concentration and ODC1 genotype were determined. Logistic regression models were used for risk estimation. RESULTS: A significant interaction was detected between dietary polyamine group and treatment with regard to adenoma recurrence (P=0.012). Significant metachronous adenoma risk reduction was observed after DFMO+sulindac treatment in dietary polyamine quartiles 1-3 (risk ratio (RR) 0.19; 95% confidence interval (CI) 0.08-0.42; P<0.0001) but not in quartile 4 (RR 1.51; 95% CI 0.53-4.29; P=0.44). However, a lower number of events in the placebo group within dietary quartile 4 confound the aforementioned risk estimates. CONCLUSION: These preliminary findings reveal complex relationships between diet and therapeutic prevention, and they support further clinical trial-based investigations where the dietary intervention itself is controlled.

Prostate cancer patients' report on communication about endocrine therapy and its association with adherence.

BACKGROUND: Endocrine therapy is a mainstay of prostate cancer therapy. Given that few data exist on patient physician communication with regard to this field of therapy and adherence, we conducted a survey of patient members of a German support organization. PATIENTS AND METHODS: We developed a structured questionnaire that was tested in a pilot version and then programmed as an online questionnaire. RESULTS: The questionnaire was completed by 694 patients. While 58 % of participants rated the information they received as comprehensive, 42 % did not. Fifty-one percentage stated that they were informed of side effects in detail, and 35 % received information on supportive treatments available in the event of side effects. Patients with higher education more often reported receiving information on side effects (p = 0.036) as well as alternatives for treatment (p = 0.001). Only 13 % stated that their questions were answered in detail, with 43 % receiving no answers or only non-detailed answers. Additional information was sought by 82 %, mostly from the Internet (67 %) and patient support groups (66 %). Seventy-six percentage experienced side effects that imposed limitations on their daily activities. Of those patients with side effects, 60 % reported that their physicians did not react to their complaints. There is a significant association between side effects in general and depression in particular and non-adherence (p < 0.01 and p = 0.002, respectively). In contrast, better information on side effects is associated with better adherence (p < 0001). CONCLUSION: In order to improve adherence, detailed information on side effects and comprehensive supportive care is most important. Physicians should not rely on written information but should rather mainly engage in direct communication.

Cyclic adenosine-3',5'-monophosphate-mediated cytotoxicity in steroid sensitive and resistant myeloma.

Multiple myeloma is a neoplastic proliferation of plasma cells. Glucocorticoids are among the most effective agents against multiple myeloma, acting through the glucocorticoid receptor to induce programmed cell death. However, some patients do not respond to glucocorticoids, and those that do respond eventually develop resistance to this therapy. Alternative strategies using drugs that mediate cytotoxicity through complementary pathways have theoretical appeal. Cyclic adenosine-3',5'-monophosphate (cAMP) derivatives are cytotoxic to a number of cell lines of lymphocytic origin. cAMP analogues activate protein kinase A, affecting cell growth and differentiation. The cascade of events initiated by cAMP derivatives and glucocorticoid, although distinct, may share some distal molecular targets. We have found that pharmacological concentrations of 8-chloro-cAMP, dibutyryl-cAMP, and 8-bromo-cAMP are cytotoxic to multiple myeloma cells, enhance glucocorticoid effects, and can kill glucocorticoid-resistant clones. cAMP analogues induce apoptosis as demonstrated by the fragmentation of myeloma DNA chromatin in a distinctive ladder pattern. In contrast to glucocorticoids, cAMP growth inhibition cannot be reversed by exogenous interleukin 6. cAMP derivatives have activity against multiple myeloma and are appropriate candidates for clinical trials.

Rehabilitation program for children with brachial plexus and peripheral nerve injury.

An aggressive and integrated physical and occupational therapy program is essential in the treatment of congenital brachial plexus injuries and other severe upper extremity nerve injuries. This article addresses the evaluation, identification of needs, establishment of goals, and the approaches to rehabilitation treatment for patients with brachial plexus palsy and other peripheral nerve injuries. Rehabilitative therapy can preserve and build on gains made possible by medical or surgical interventions; however, therapy is vital to these children regardless of whether surgery is indicated. The therapist uses a problem-solving approach to evaluate the patient and select appropriate occupational and physical therapy treatment modalities. Therapy is continually adjusted based on each child's unique needs. An understanding of the therapy principles aids in making appropriate referrals and prescriptions, and helps to coordinate care between the therapist, pediatrician, neurologist, and surgeon.

Epidemiology of nasopharyngeal carcinoma in the United States: improved survival of Chinese patients within the keratinizing squamous cell carcinoma histology.

BACKGROUND: This study examined potential survival differences among nasopharyngeal carcinoma (NPC) patients from various ethnicities in the United States. PATIENTS AND METHODS: A total of 2436 newly diagnosed NPC patients from 1992 to 2002 were analyzed from the population-based Surveillance, Epidemiology, and End Results (SEER) program. Five-year survival rate estimates and Kaplan-Meier survival curves were calculated. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. RESULTS: By multivariate analyses, early age of diagnosis, localized stage at presentation (versus distant, HR=0.35; P<0.0001), radiation therapy (versus none; HR=0.48; P<0.0001), undifferentiated non-keratinizing carcinoma (versus keratinizing squamous cell carcinoma; HR=0.67; P<0.0001), and Chinese ethnicity (versus Caucasian; HR=0.78; P=0.0010) were associated with improved survival. Within keratinizing squamous cell carcinoma histology, the survival advantage of Chinese patients remained even after adjustment for other prognostic factors. CONCLUSIONS: The significant survival advantage of Chinese NPC patients within the keratinizing squamous cell carcinoma histology contributed largely to Chinese ethnicity being an independent and favorable prognostic factor for survival in NPC.

Long-term survival differences for bronchiolo-alveolar carcinoma patients with ipsilateral intrapulmonary metastasis at diagnosis.

BACKGROUND: It has been suggested that the current staging system does not accurately reflect survival outcomes for advanced bronchiolo-alveolar carcinoma (BAC) patients. METHODS: We conducted a case-only analysis of US Surveillance, Epidemiology, and End Results (SEER) data (1998-2002). Overall survival (OS) and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: 2345 incident cases of BAC were analyzed, including 707 patients with stage IIIB or IV BAC. Patients with stage IIIB BAC due to multiple lesions in the same lobe (n=93) had significantly improved median OS (46m) and LCSS (>58m) compared to other stage IIIB BAC patients (n=111; OS=9m, P<0.0001; LCSS=10m, P<0.0001). Among stage IV BAC patients, those with intrapulmonary metastasis (n=278) had significantly improved median OS (13m) and LCSS (15m) compared to those with distant metastasis (n=225; OS=7m, P<0.0001; LCSS=7m, P=0.0001). These survival differences persisted after adjustment for age, gender, ethnicity, and surgical treatment status. CONCLUSIONS: Among stage IIIB and IV BAC patients, those presenting with ipsilateral intrapulmonary metastasis have improved survival outcomes. Our results add further support for modification to the current staging system for BAC.

Expression of vascular endothelial growth factor mRNA in GI-101A and HL-60 cell lines.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that has a strong association with growth and metastasis of various cancers. We analyzed the expression of VEGF mRNA levels in human breast-tumor derived GI-101A cells and in human promyelocytic leukemia derived HL-60 cells using RT-PCR technique. During our RT-PCR analysis we detected the expression of three splice variants of VEGF mRNA at 400, 520 and, 650 bp lengths, which were amplified by a single set of VEGF specific forward and reverse primers. The three RT-PCR products detected by us in these cells correspond to the mRNA splice variants coding for the three isoforms of VEGF respectively, VEGF(121), VEGF(165), and VEGF(189). Treatment of GI-101A and HL-60 cells with phorbol 12, 13-dibutyrate (PDB) or diethylstilbestrol (DES) resulted in a significant increase of VEGF mRNA levels in a dose dependent manner. Both treatments increased the levels of all three splice variants of VEGF mRNA and a maximum increase was detected with 10 microM concentrations of PDB or DES treatments after 2 h. Interestingly, both PDB and DES mediated stimulation of VEGF mRNA expression was completely blocked by the PKC inhibitor chelerythrine. Quantitation of VEGF levels by ELISA technique confirmed that changes seen in mRNA levels following different treatments altered the release of VEGF. Our results suggest that PDB and DES mediated effects on VEGF expression in GI-101A and HL-60 cells occur at the gene transcription level.

8Cl-cAMP cytotoxicity in both steroid sensitive and insensitive multiple myeloma cell lines is mediated by 8Cl-adenosine.

We have examined the cytotoxic effects of cyclic adenosine-3', 5'-monophosphate (cAMP) derivatives on multiple myeloma cells lines and determined that the 8-Chloro substituted derivative (8Cl-cAMP) is one of the most potent. We report here that 8Cl-cAMP is cytotoxic to both steroid sensitive and insensitive myeloma cells with a half maximal concentration of approximately 3 micromol/L. 8Cl-cAMP toxicity in myeloma cells is dependent on phosphodiesterase activity in the serum of cell culture medium. A metabolite of 8Cl-cAMP, 8-Chloro-adenosine (8Cl-AD), kills myeloma cells as effectively as 8Cl-cAMP. Adenosine deaminase (ADA) converts 8Cl-AD into 8Cl-inosine and abrogates the cytotoxic effects of 8Cl-cAMP, 8Cl-AMP, and 8Cl-AD, as does 5-(p-Nitrobenzyl)-6-Thio-Inosine (NBTI), an inhibitor of nucleoside uptake. These data suggest that 8Cl-cAMP must be converted to 8Cl-AD and that 8Cl-AD is the compound that enters the cell. Contrary to glucocorticoid-mediated cell death in myeloma cells, the pathway of 8Cl-AD-mediated cell death appears to be independent of interleukin-6 (IL-6) actions. Although the exact mode of action for this agent is currently unknown, its ability to kill steroid sensitive and insensitive multiple myeloma cells in an IL-6 independent fashion may offer exciting new therapeutic options.