Background and Objectives Sarcopenia, which is subclinical loss of skeletal muscle mass, is commonly observed in patients with malignancy. The objective of this study is to determine the correlation between sarcopenia and operative complications following pancreatectomy for cancer. Methods A retrospective review of a pancreatectomy database was performed. The Hounsfield Unit Average Calculation (HUAC) of the psoas muscle, a marker of muscle density and fatty infiltration, was measured from preoperative CT scans. Complications were graded and multivariate logistic regression analysis was performed. Results One hundred eighteen patients met criteria for analysis; the overall morbidity rate was 78.8% (n =93). There were 31 (26.3%) patients who met criteria for sarcopenia using the HUAC. When analyzed as a continuous variable, sarcopenia was an independent predictor of major grade III complications, length of stay, intensive care unit admission, delayed gastric emptying, and infectious, gastrointestinal, pulmonary, and cardiac complications. Conclusions These data suggest that sarcopenia as measured with the HUAC, a value that can be obtained from a preoperative CT scan, is a significant independent predictor of surgical outcome and can be used to improve patient selection and informed consent prior to pancreatectomy in patients with cancer.
The toxicity of pharmacological ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Since pancreatic cancer cells are sensitive to H2O2 generated by ascorbate they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacological ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in non-tumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacological ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacological ascorbate as a radiosensitizer in the treatment of pancreatic cancer.
Objective To describe the indications for total abdominal hysterectomy for women with nonmalignant disease and to determine the immediate (initial ten days) and medium term outcome. Design A prospective cohort study. Setting Three district general hospitals in shire counties, two in outer London and one London teaching hospital. Subjects Three hundred and sixty‐six women undergoing total abdominal hysterectomy (with or without other procedures) for nonmalignant disease. Interventions Self‐completed patient questionnaires before and ten days, six weeks and three months after surgery. Data extracted from patients' hospital case notes. Main outcome measures Complications plus change in symptoms, urinary and bowel function, general health status, sexual function, activities of daily living and quality of life. Results The principal indications were bleeding, pain or both. Symptoms were severe enough to be socially debilitating and have a major impact on lifestyle. Otherwise, the women were in good health. During the first ten post‐operative days the women suffered more pain, urinary discomfort, constipation and a reduction in their ability to perform activities of daily living. Urinary (25%) and wound (25%) infections were the commonest complications. At the same time, significant improvements in psychological health occurred. By six weeks, the principal symptoms had resolved for 95% of the women and early adverse effects on urinary and bowel function had settled. This was reflected in improvements in health status and quality of life including sexual activity. Despite this, these changes did not meet the pre‐operative expectations of some women. Conclusions Most women reported substantial benefits from hysterectomy. However, women should be warned about early, transient adverse effects. These findings can serve as a benchmark for nonexperimental evaluations of the effectiveness of new treatment modalities.
This study generates further knowledge about rural nursing and contributes insight into the importance of handover implementation method--areas that are not widely documented in existing literature.
In Thailand, the crude death rate from stroke is 10.9/100,000 population and increasing. Unlike Western countries where community rehabilitation programmes have been established to provide services following the acute stage of stroke recovery, there is no stroke rehabilitation team in the community in Thailand. Therefore, family caregivers are the primary source for ongoing care and support. While family members accompany patients during their hospitalisation, they receive little information about how to assist their relatives, and as a result feel inadequately trained, poorly informed and dissatisfied with the support that is available after discharge. Family caregivers report that they suffer both physically and psychologically and find themselves overwhelmed with strain, experiencing burden and exhaustion. This study aimed to develop and implement a nurse-led Supportive Educative Learning programme for family caregivers (SELF) of stroke survivors in Thailand and to evaluate the effect of the SELF programme on family caregiver's strain and quality of life. This was a non-randomised comparative study with concurrent controls, using a two-group pre-test and post-test design. A total of 140 stroke survivors and 140 family caregivers were recruited; 70 patients/caregiver pair in each group. Caregivers of patients admitted to the intervention hospital following an acute stroke received the intervention, while caregivers of patients admitted to the comparison hospital received the usual care provided at the hospital. The data were collected prior to discharge of the patients and after 3 months. The family caregivers in the intervention group had a significantly better quality of life than the comparison group (GHQ-28 at discharge t = 2.82, d.f. = 138, P = 0.006; and at 3 months t = 6.80, d.f. = 135, P < 0.001) and they also reported less strain (Caregiver Strain Index at discharge t = 6.73, d.f. = 138, P < 0.001; and at 3 months t = 7.67, d.f. = 135, P < 0.001). This research demonstrated that providing education and support to the family caregiver of stroke survivors can reduce caregiver strain and enhance their quality of life.
Individual mutations in the tumor suppressor TP53 alter p53 protein function. Some mutations create a non-functional protein, whereas others confer oncogenic activity, which we term ‘oncomorphic’. Since mutations in TP53 occur in nearly all ovarian tumors, the objective of this study was to determine the relationship of oncomorphic TP53 mutations with patient outcomes in advanced serous ovarian cancer patients. Clinical and molecular data from 264 high-grade serous ovarian cancer patients uniformly treated with standard platinum- and taxane-based adjuvant chemotherapy were downloaded from The Cancer Genome Atlas (TCGA) portal. Additionally, patient samples were obtained from the University of Iowa and individual mutations were analyzed in ovarian cancer cell lines. Mutations in the TP53 were annotated and categorized as oncomorphic, loss of function (LOF), or unclassified. Associations between mutation types, chemoresistance, recurrence, and progression-free survival (PFS) were calculated. Oncomorphic TP53 mutations were present in 21.3% of ovarian cancers in the TCGA dataset. Patients with oncomorphic TP53 mutations demonstrated significantly worse PFS, a 60% higher risk of recurrence (HR=1.60, 95% confidence intervals 1.09, 2.33, p=0.015), and higher rates of platinum resistance (χ2 test p=0.0024) when compared with single nucleotide mutations not categorized as oncomorphic. Furthermore, tumors containing oncomorphic TP53 mutations displayed unique protein expression profiles, and some mutations conferred increased clonogenic capacity in ovarian cancer cell models. Our study reveals that oncomorphic TP53 mutations are associated with worse patient outcome. These data suggest that future studies should take into consideration the functional consequences of TP53 mutations when determining treatment options.
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