Efficacy of the end-of-life nursing care continuing education program for nurses in general wards in Japan.

This study aimed to examine effectiveness of the End-of-life nursing care continuing education program for general ward nurses. A nonrandomized, before-after trial was conducted. The program was implemented for 25 nurses. The contents of the program consisted of the family assessment, general symptom management and practical use of theories and models regarding end-of-life nursing care. The primary outcome, implementation ability of end-of-life nursing care, was significantly improved after the program; improvements continued even at 2 months after. Similar results were obtained for nurses' confidence and knowledge concerning end-of-life nursing care. As for attitude toward end-of-life care, participants' scores were further elevated after the program. The participants rated the usefulness of the program as high. The effectiveness of the program was suggested from these results. In the future, this program should be widely used for in-service training.

Can gradual dose titration of ketamine for management of neuropathic pain prevent psychotomimetic effects in patients with advanced cancer?

BACKGROUND: Ketamine is often used to manage neuropathic pain in patients with cancer. However, it occasionally causes psychotomimetic effects such as vivid dreams, nightmares, illusions, hallucinations, and altered body image. OBJECTIVE: To examine whether gradual dose titration of ketamine for management of neuropathic pain prevents psychotomimetic effects in patients with advanced cancer. METHODS: This was a retrospective chart review. We administered ketamine when neuropathic pain in patients with advanced cancer became refractory to opioids and oral adjuvant analgesics. The starting dose of ketamine was 10 mg/d by continuous intravenous infusion. The dose was gradually increased by 10 mg/d every 4 to 6 hours to 50 mg/d or until the pain was relieved. It was subsequently increased by 25 mg/d every 12 to 24 hours until the pain was relieved. RESULTS: For this study, we enrolled 46 patients with advanced cancer. The mean age was 52.2 ± 16.9 years. The mean dose at onset of action and maximum dose of ketamine were 56 ± 58 and 272 ± 214 mg/d, respectively. The mean pain intensity (numerical rating scale) decreased significantly from 7.3 ± 2.0 to 3.5 ± 2.2 after the administration of ketamine (P < .01). The effectiveness was 69.5%. No psychotomimetic effect of less than 300 mg/d was observed during the introduction phase even though psychotropic drugs were not prescribed. Mild sedation was observed in 3 patients (7%) as the only adverse effect during the introduction phase. CONCLUSION: Gradual dose titration of ketamine for management of neuropathic pain can prevent psychotomimetic effects in patients with advanced cancer.

An observational study of insomnia and nightmare treated with trazodone in patients with advanced cancer.

Patients with cancer often experience insomnia. Nightmares are also a strong factor that interferes with the maintenance of comfortable and satisfying sleep. However, the prevalence and standard treatment of nightmares in patients with cancer have not been established yet. We aimed to treat insomnia and nightmares with trazodone. From 2008 to 2011, trazodone was prescribed to 30 patients with cancer who reported experiencing insomnia with or without nightmares to the palliative care team in Osaka University Hospital. Effective treatment was seen in 15 patients (50%). Four patients with cancer reported having severe nightmares and 2 patients had beneficial effects, with frightening dreams transformed into acceptable ones. Trazodone may be an effective drug for the treatment of insomnia and nightmares in patients with advanced cancer.

Effect of green tea extract on reactive oxygen species produced by neutrophils from cancer patients.

BACKGROUND/AIM: Oxidative stress in cancer patients has been demonstrated to be partly mediated by neutrophils. Although it is reported that natural antioxidants, such as green tea extract, reduce oxidative stress, there is limited evidence of their effects in cancer patients. This study aimed to determine the effect of green tea extract on reactive oxygen species produced by neutrophils from cancer patients. MATERIALS AND METHODS: Peripheral blood samples were obtained from eighteen patients with advanced cancer. Green tea extract was added to the blood samples with luminol on Mebiol gel, and luminol-dependent chemiluminescence was measured to monitor the production of reactive oxygen species from migrated neutrophils into the gel, at 37°C. RESULTS: Luminol-dependent chemiluminescence was significantly down-regulated in the presence of green tea extract in a concentration-dependent manner. CONCLUSION: These results indicate the antioxidant effect of green tea extract on reactive oxygen species produced by neutrophils, which may be effective in reducing oxidative stress in cancer patients.

WT1 peptide vaccine stabilized intractable ovarian cancer patient for one year: a case report.

UNLABELLED: We report on Wilms tumor (WT1) peptide immunotherapy in a patient with intractable ovarian cancer patient over an extended period. CASE REPORT: Immunotherapy using WT1 peptide has been undergoing clinical trials for gynecological cancer. We used WT1 peptide vaccination to treat a 53-year-old woman suffering from ovarian cancer with peritoneal dissemination. After 2 months, her pleural and cardiac effusion had disappeared, and the sum of the longest diameter of the target lesion (in the pelvic mass) was reduced. There was a weak positive correlation between CA125 and mononuclear phagocyte/lymphocyte ratio (Spearman's ϱ=0.275, p=0.015). Intradermally administered WT1 peptide vaccination in a case of intractable ovarian cancer stabilized the disease over the course of one year. However, the immunotherapeutic mechanism of WT1 peptide and immunological escape mechanism for carcinoma cells remain to be elucidated.

WT1 expression correlates with angiogenesis in endometrial cancer tissue.

BACKGROUND: No direct comparison has been made of the relationship between the expression of Wilms' tumor gene WT1 within tumor cells and angiogenesis in vivo. MATERIALS AND METHODS: A series of 70 endometrial cancer patients who had undergone a curative resection was studied by immunohistochemistry to determine the correlation between WT1 expression, angiogenesis (proliferation of endothelial cell adhesion molecule-1, PECAM-1/CD31) and angiogenic growth factor (vascular endothelial growth factor, VEGF). RESULTS: A strong association was found between WT1 expression score and mean vascular density (p<0.001, n=70, ϱ=0.568). Immunohistochemistry of serial sections revealed that WT1 and VEGF were co-expressed in the same area of endometrial cancer tissue. CONCLUSION: Tumor-produced WT1, which may regulate the expression of VEGF, is found to be associated with induction of angiogenesis in endometrial cancer.

Can anti-infective drugs improve the infection-related symptoms of patients with cancer during the terminal stages of their lives?

BACKGROUND: Appropriate use of anti-infective drugs is essential in clinical practice. No evidence-based guidelines or protocols have been published on the appropriate use of anti-infective drugs in patients receiving palliative care as yet. METHODS: The medical records, which included the demographic data of patients, anti-infective drug use, bacteriologic findings, symptoms, and hematologic findings were reviewed retrospectively to determine the potential factors that contribute to symptom improvement of patients in terminal phase. RESULTS: Seventy-one patients (64%) who received anti-infective drugs and had a total of 326 episodes of infection were assessed. Symptom improvement was seen in 33.1%. A total of 22.6% of episodes were started on anti-infective drugs during the last week of life and the symptom improvement in these episodes was 9.2%. Symptom improvement was hardly observed when the anti-infective drug was administered during the last week of life. The association between the decrease in the C-reactive protein (CRP) levels, the decrease of the leukocyte count, reduction of fever, and symptom improvement was determined. The decrease of CRP levels was 42.4%; leukocyte, 56.7%; and reduction of fever was 28.4%. The symptom improvement of individual treatment history was also investigated. The symptom improvement of the group who took positive treatment such as chemotherapy, radiotherapy, surgery, and catheter placement was significantly lower than that of no-treatment group. CONCLUSIONS: Active cancer treatment probably induces the symptoms related to infection and the use of anti-infective drugs. Unnecessary and excessive treatment should be avoided, and the symptoms should be managed with consideration of the patient's state of mind in order to improve the quality of life of terminally ill patients.

Correlation between WT1 expression and cell proliferation in endometrial cancer.

BACKGROUND: The Wilms' tumor gene WT1 is overexpressed in endometrial cancer. Although recent studies have revealed that WT1 is a new prognostic factor, it remains unclear whether WT1 plays a pathophysiological role including cell proliferation. PATIENTS AND METHODS: A series of 70 endometrial cancer patients who had undergone a curative resection was studied by immunohistochemistry to determine the correlation between WT1 expression and cell proliferation (proliferating cell nuclear antigen; PCNA). RESULTS: WT1 expression was observed in 64 cases (91%). WT1 expression was associated with advanced FIGO stage (p=0.0228), myometrial invasion (p=0.0114) and high-grade histological differentiation (p=0.0004), indicating up-regulation of WT1 expression with tumor progression. A positive correlation between PCNA labeling index and score of WT1 expression was observed (p=0.0081, rho=0.319). CONCLUSION: These results showed that WT1 might regulate cell proliferation in endometrial cancer.

High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer.

Vitamin C (ascorbic acid, ascorbate) has a controversial history in cancer treatment. Emerging evidence indicates that ascorbate in cancer treatment deserves re-examination. As research results concerning ascorbate pharmacokinetics and its mechanisms of action against tumor cells have been published, and as evidence from case studies has continued to mount that ascorbate therapy could be effective if the right protocols were used, interest among physicians and scientists has increased. In this review, high-dose vitamin C therapy in cancer treatment is re-evaluated.

Immunohistochemical detection of WT1 protein in endometrial cancer.

BACKGROUND: The Wilms' tumor gene WT1 is overexpressed in various kinds of solid tumors. However, it remains unclear whether WT1 plays a pathophysiological role in endometrial cancer. PATIENTS AND METHODS: A series of 70 endometrial cancer patients who had undergone a curative resection was studied to determine the correlation between WT1 expression, clinicopathological characteristics and prognosis. Tissue specimens were evaluated for WT1 expression by immunohistochemistry. RESULTS: The expression of WT1 was strong in 31 patients (44%) and weak in 39 patients (56%). WT1 overexpression was associated with advanced FIGO stage (p=0.0266), myometrial invasion (p=0.0477) and high-grade histological differentiation (p=0.0049). The expression level of WT1 was found to be a significant predictor of disease relapse in univariate analysis (p=0.0233), but not in multivariate analysis (p=0.4757). CONCLUSION: These results suggested that tumor-produced WT1 provided additional prognostic information in endometrial cancer patients.

Measurement of electron density in dual-energy x-ray CT with monochromatic x rays and evaluation of its accuracy.

Information on electron density is important for radiotherapy treatment planning in order to optimize the dose distribution in the target volume of a patient. At present, the electron density is derived from a computed tomography (CT) number measured in x-ray CT scanning; however, there are uncertainties due to the beam hardening effect and the method by which the electron density is converted from the CT number. In order to measure the electron density with an accuracy of +/-1%, the authors have developed dual-energy x ray CT using monochromatic x rays. They experimentally proved that the measured linear attenuation coefficients were only a few percent lower than the theoretical ones, which led to an accuracy within 2% for the electron density. There were three factors causing inaccuracy in the linear attenuation coefficient and the electron density: the influence of scattered radiation, the nonlinearity in the detector response function, and a theoretical process to derive the electron density from the linear attenuation coefficients. The linear attenuation coefficients of water were experimentally proved to differ by 1%-2% from the theoretical one even when the scattering effect was negligible. The nonlinearity of the response function played an important role in correcting the difference in the linear attenuation coefficient. Furthermore, the theoretical process used for deriving the electron density from the linear attenuation coefficients introduces about 0.6% deviation from the theoretical value into the resultant electron density. This deviation occurs systematically so that it can be corrected. The authors measured the electron densities for seven samples equivalent to soft tissue in dual-energy x-ray CT, and finally obtained them with an accuracy of around +/-1%.

Dose distribution of a 125 keV mean energy microplanar x-ray beam for basic studies on microbeam radiotherapy.

A multislit collimator was designed and fabricated for basic studies on microbeam radiation therapy (MRT) with an x-ray energy of about 100 keV. It consists of 30 slits that are 25 microm high, 30 mm wide, and 5 mm thick in the beam direction. The slits were made of 25 microm-thick polyimide sheets that were separated by 175 microm-thick tungsten sheets. The authors measured the dose distribution of a single microbeam with a mean energy of 125 keV by a scanning slit method using a phosphor coupled to a charge coupled device camera and found that the ratios of the dose at the center of a microbeam to that at midpositions to adjacent slits were 1050 and 760 for each side of the microbeam. This dose distribution was well reproduced by the Monte Carlo simulation code PHITS.

Expression of NLRP7 (PYPAF3, NALP7) protein in endometrial cancer tissues.

BACKGROUND: Nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain-containing 7 (NLRP7) (pyrin-containing apoptotic protease activating factor-1-like protein 3; PYPAF3, NACHT domain-, leucine-rich repeat, and pyrin domain-containing 7; NALP7) has been thought to contribute to innate immunity and inflammation. Although expression of NLRP7 in human seminoma tissues and several cancer cell lines has been demonstrated, the pathophysiological and prognostic importance in cancer tissues has not been defined. MATERIALS AND METHODS: A series of 70 endometrial cancer cases that had undergone curative resection was studied to determine the correlation between NLRP7 expression and clinico-pathological characteristics in human endometrial cancer tissue. Tissue specimens were evaluated for NLRP7 by immunohistochemistry. RESULTS: NLRP7 expression was positive in cancer cells in 7 cases (10%). There was a statistical relationship between the depth of tumor invasion and NLRP7 expression (p=0.0326). NLRP7 expression showed a trend for being associated with poor prognosis. CONCLUSION: Tumor-produced NLRP7, associated with myometrial invasion, might provide additional prognostic information in endometrial cancer patients.

Dosimetry for a microbeam array generated by synchrotron radiation at SPring-8.

A microbeam array was formed with a multi-slit collimator (MSC) for research on radiation therapy (MRT). Kodak EDR2 film was used to measure the dose distribution of the microbeam array. The calibration curve of optical density of the film with respect to a dose was established using a standard Farmer chamber and (60)Co gamma-ray source. The peak dose of 3.6 Gy/s at the maximum was derived from the film dosimetry using the calibration curve. The uncertainty was estimated to be 5% which was mainly attributed to the uncertainty of the calibration. It was found that the ionization chamber used for monitoring the dose during the MRT experiments gave lower dose by about 30% than the dose derived from the film dosimetry.

Cyclooxygenase-2 expression correlates with apoptosis and angiogenesis in endometrial cancer tissue.

BACKGROUND: Recent experimental studies have indicated that cyclooxygenase-2 (COX-2) suppresses tumor-cell apoptosis and induces intratumoral angiogenesis. PATIENTS AND METHODS: A series of 70 endometrial cancer cases that had undergone a curative resection was studied to determine the correlation between COX-2 expression, apoptosis and angiogenesis in human endometrial cancer tissue. Tissue specimens were evaluated for COX-2, single-strand DNA (ssDNA, apoptosis) and CD31 (angiogenesis) by immunohistochemistry. RESULTS: COX-2 expression was positive exclusively in cancer cells in 37 cases (53%). The apoptotic index was lower in COX-2-positive cancer cells than COX-2-negative cases. Microvessel density was higher in COX-2-positive cancer cases than COX-2-negative cases. COX-2 overexpression was significantly associated with poor prognosis. CONCLUSION: These results suggested that tumor-produced COX-2, which was associated with inhibiting apoptosis and promoting angiogenesis, provided additional prognostic information in endometrial cancer patients.

Effect of lectins on the transport of food factors in caco-2 cell monolayers.

The effect of three plant lectins, soybean lectin (SBA), Japanese jack bean lectin (CGA), and wheat germ lectin (WGA), on the transport of various food factors, such as isoflavones, quercetin, dipeptides, and calcium ions, were investigated by use of an intestinal tract model, Caco-2 cell monolayers. The lectins increased the isoflavone transport but had no effect on aglycon transport. SBA increased the transport of quercetin glycosides, whereas CGA and WGA had no effect. The lectins increased the transport of calcium ions but showed no effect on the transport of dipeptides, carnosine, and anserine. Although SBA did not change the transepithelial electrical resistance (TER) value of the Caco-2 cell monolayers, CGA and WGA decreased the TER value. These results indicate that plant lectins affect the transport of food factors in different manners, presumably due to their specific sugar binding activity.

Expression of Tn and sialyl-Tn antigens in endometrial cancer: its relationship with tumor-produced cyclooxygenase-2, tumor-infiltrated lymphocytes and patient prognosis.

BACKGROUND: Although many tumors arising from epithelial tissues produce mucins, little is known regarding the biological significance of mucins in cancer. Recent researches have revealed that mucins produced by cancer cells play a critical role in the initial induction of cyclooxygenase (COX)-2 in the tumor microenvironment. Moreover, the consequence of abnormal glycosylation and overexpression of mucins includes suppression of the host-immune function. MATERIALS AND METHODS: The expression of Tn/sialyl-Tn (s-Tn) antigen and its impact on COX-2 expression by tumor cells and infiltration of CD8+ T-cell into the cancer cell nest (nest CD8) in endometrial cancer was evaluated. Tissue specimens from 70 endometrial cancer patients who had undergone a curative resection were evaluated for Tn/s-Tn antigen, COX-2 and CD8 by immunohistochemistry. RESULTS: The overexpression of Tn and s-Tn antigen was significantly correlated with COX-2 overexpression (p <0.005 and p <0.001, respectively). There was a significant association between s-Tn overexpression and low infiltration of nest CD8 (p<0.05). Strong expression of s-Tn antigen was significantly associated with poor prognosis (p < 0. 005). Among several prognostic factors, s- Tn expression remained the strong independent predictor of survival by multivariate analysis (p<0.05). CONCLUSION: These results suggested that tumor-produced mucins, which were associated with COX-2 induction and immunosuppression, provided additional prognostic information in endometrial cancer patients.

Multiple roles of cyclooxygenase-2 in endometrial cancer.

Cyclooxygenase-2 (COX-2) plays a critical role not only in maintenance of the endometrium during the menstrual cycle, but also in the progression of endometrial cancer. The role of COX-2 in tumor growth and development is complex and multifaceted. This review presents evidence for the expression of COX-2 being linked to angiogenesis, tumor cell apoptosis, tumor cell growth, metastasis and local immunosuppression in cancer progression. It also outlines the clinicopathological and prognostic significance of COX-2 in endometrial cancer.

Role of tumor-associated macrophages (TAM) in advanced gastric carcinoma: the impact on FasL-mediated counterattack.

BACKGROUND: Exactly what role does tumor-derived Fas ligand (FasL) play in cancer: maintaining the immune privilege site or inducing a pro-inflammatory effect? One possible hypothesis is that tumor-associated macrophages (TAM) act as the mediator that enables apoptosis of anti-tumor immune cells without FasL-related inflammation. We have evaluated the tumor FasL expression and TAM along the tumor margin and/or in cancer stroma, and their impact on the infiltration of immune-competent cells into the tumor nest. PATIENTS AND METHODS: Tissue specimens from consecutive 84 advanced gastric carcinoma patients, who had undergone a curative resection, were evaluated for TAM (CD68+ cells), tumor FasL expression and immune status (CD8 + T cells). RESULTS: A high number of TAM significantly correlated with lymph node metastasis, intestinal type tumor and FasL expression. Although TAM had a tendency for an inverse correlation with the number of CD8+ T cells within the tumor nest (nest CD8) (p=0.0592), there was no correlation between FasL expression and nest CD8 (p=0.2158). This inverse association was found to be stronger in cases with both FasL-positive and high TAM tumors than in others (p=0.0139). The combination parameter of FasL-positive and high TAM became an independent prognostic factor in Cox's multivariate analysis, along with the pT status, nest CD8 and tumor cell apoptosis. CONCLUSION: We suggest that TAM works harmoniously with tumor-derived FasL and serves as a barrier against the infiltration of CD8+ T cells into the cancer nest.

Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma.

Although there are several hypotheses explaining the mechanisms of immune-privileged status of malignant tumor, the exact pathway has yet to be explored. Cyclooxygenase (COX)-2 plays a vital role in prognosis of cancer patients in terms of contribution to neoangiogenesis and apoptosis inhibition; however, the impact of COX-2 in immunomodulation has not been reported. We have evaluated the expression of COX-2 and its impact on infiltration of immune-competent cells into the tumor cell nest in endometrial carcinoma. Tissue specimens from 70 endometrial carcinoma patients who had undergone a curative resection were evaluated for COX-2 expression and host immune status (CD8+ T cells). COX-2 expression was associated with FIGO stage and myometrial invasion, but there was no statistically significant impact. CD8+ T cells within cancer cell nest (Nest CD8) were inversely correlated with the expression level of COX-2 (p = 0.0006). Nest CD8 became an independent predictor of patient survival (Hazard ratio = 10.300, p = 0.0304) in Cox's multivariate analysis. The expression level of COX-2 was found to be a significant predictor of disease relapse in univariate analysis (p = 0.0294) but not in multivariate analysis (p = 0.5949). In conclusion, increased nest CD8 produced a survival advantage in endometrial carcinoma patients. Moreover, tumor-produced COX-2, which reduces the infiltration of CD8+ T cells into cancer cell nests, may allow tumors to avoid immune surveillance.