Epstein-Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature.

BACKGROUND: Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein-Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor. CASE PRESENTATION: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma originates only in the liver or spleen, causes no symptoms, and is more common in middle-aged Asian women. It has no characteristic imaging features, which partially explains why the inflammatory pseudotumor variant of follicular dendritic cell sarcoma is difficult to diagnose. Pathologically, the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has spindle cells mixed with inflammatory cells and is variably positive for follicular dendritic cell markers (CD21, CD23, and CD35) and Epstein-Barr virus-encoded RNA. On genetic analysis, patients with this tumor high levels of latent membrane protein 1 gene expression and extremely low levels of host C-X-C Chemokine Receptor type 7 gene expression, indicating that the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has a latent Epstein-Barr virus type 2 infection. CONCLUSIONS: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is an Epstein-Barr virus-associated tumor and a favorable prognosis by surgical resection, similar to Epstein-Barr virus-associated gastric cancer.

Gastrectomy with or without omentectomy for cT3-4 gastric cancer: a multicentre cohort study.

BACKGROUND: Omentectomy is performed widely for locally advanced gastric cancer to prevent disease recurrence. However, its clinical benefit is unknown. METHODS: This retrospective cohort study compared the outcome of gastrectomy with preservation of the omentum (GPO) and gastrectomy with resection of the omentum (GRO) among patients with cT3-T4 gastric cancer who underwent gastrectomy between 2006 and 2012 in one of five participating institutions. A consensus conference identified 28 variables potentially associated with outcome after gastrectomy for the estimation of propensity scores, and propensity score matching (PSM) was undertaken to control for possible confounders. Postoperative surgical outcomes, overall survival and disease recurrence were compared between GPO and GRO. RESULTS: A total of 1758 patients were identified, of whom 526 remained after PSM, 263 in each group. Median follow-up was 4·9 (i.q.r. 3·1-5·9) years in the GRO group and 5·0 (2·5-6·8) years in the GPO group. The incidence of postoperative complications of Clavien-Dindo grade III or more was significantly higher in the GRO group (17·5 versus 10·3 per cent; P = 0·016). Five-year overall survival rates were 77·1 per cent in the GRO group and 79·4 per cent in the GPO group (P = 0·749). There were no significant differences in recurrence rate or pattern of recurrence between the groups. CONCLUSION: Overall survival and disease recurrence were comparable in patients with cT3-4 gastric cancer who underwent GPO or GRO.

ANTECEDENTES: La omentectomía se realiza ampliamente en el cáncer gástrico localmente avanzado para prevenir la recidiva de la enfermedad. Sin embargo, se desconoce su beneficio clínico. MÉTODOS: Este estudio retrospectivo comparó el resultado de la gastrectomía con preservación del omento (gastrectomy with preservation of the omentum, GPO) con la gastrectomía con resección del omento (gastrectomy with resection of the omentum, GRO) para el cáncer gástrico con estadio clínico T3/T4. Se incluyeron pacientes sometidos a gastrectomía por cáncer gástrico clínico T3/T4 (2006-2012) y se recogieron datos relevantes de 5 hospitales participantes. A través de una conferencia de consenso se identificaron 28 variables potencialmente asociadas con el resultado tras la gastrectomía, mediante las cuales se estimaron las puntuaciones de propensión, utilizándose el emparejamiento por puntuación de propensión (propensity score matching, PSM) para el control de posibles factores de confusión. Los resultados quirúrgicos postoperatorios, la supervivencia global y la recidiva de la enfermedad se compararon entre las gastrectomías con GPO y GRO. RESULTADOS: En total, se identificaron 1.758 pacientes, seleccionándose 526 (263 GRO y 263 GPO) tras el PSM. La mediana (rango intercuartílico) de seguimiento fue de 4,9 años (3,1-5,9) en el grupo GRO y de 5,0 años (2,5-6,8) en el grupo GPO. La incidencia de complicaciones postoperatorias de Clavien-Dindo grado III o más alto fue significativamente más elevada en el grupo GRO que en el grupo GPO (17,1% versus 9,1%; P = 0,010). La supervivencia global a los 5 años fue del 77,1% para el grupo GRO y del 79,4% para el grupo GPO (P = 0,749). No hubo diferencias estadísticamente significativas en la tasa de recidiva o patrón de recidiva entre ambos grupos. CONCLUSIÓN: La supervivencia global y la recidiva de la enfermedad son comparables en pacientes con cáncer gástrico estadio clínico T3-4 sometidos a GPO o GRO.

A comparison of operative and margin outcomes from surgeon learning curves in robot assisted radical prostatectomy in a changing referral practice.

Introduction The aim of this study was to explore the impact of increasing proportions of high risk referrals on surgical margin outcomes of a surgeon's learning curve in robotic prostatectomy. Methods All patients in this study underwent robot assisted radical prostatectomy (RARP) performed by three different consultant urological surgeons. Data collected included preoperative clinical stage, Gleason score and prostate specific antigen levels, which were used to risk stratify patients according to National Institute for Health and Care Excellence criteria. Oncological clearance was assessed by overall and stage specific positive margin status. Comparisons were made between each surgeon for the first and second 50 consecutive cases. Results For the three surgeons, there was a progressive increase in the proportion of high risk cases referred accompanied by a corresponding decline in low risk disease (p<0.001). Postoperative pathology also showed an upward trend in pT3 cases across the three eras. There was no statistical difference in overall positive margin rates between the surgeons. The overall rates were 12%, 20% and 23% for the first 50 cases, and 32%, 36% and 21% for the second 50 cases for the three surgeons respectively. Conclusions Our series demonstrates an upward trend in the risk profile of men referred for robotic prostatectomy over a nine-year period. Despite this, there was minimal impact on pathological and surgical outcomes among our surgeons, who were at the initial stages of their RARP learning curve. Our results suggest that there is no requirement for an active case selection bias against patients with high risk disease for surgeons newly embarking on their RARP learning experience.

Renal pseudoaneurysm: a rare and potentially fatal complication following ureteroscopy and laser fragmentation of stones.

Ureteroscopy and laser fragmentation of stones is a commonly used method to treat ureteric and renal calculi. We report the exceedingly rare finding of a renal pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser stone fragmentation, which was successfully managed with angioembolisation.

Evaluation of economic burden of colonic surgical site infection at a Japanese hospital.

BACKGROUND: Several reports have been published regarding cost increases attributable to surgical site infections (SSIs) in Europe and the USA. However, such studies have been limited in Japan. AIM: To evaluate the economic burden of colorectal SSIs on hospitals in Japan. METHODS: This study was undertaken at a Japanese university hospital. Amongst 265 patients who had undergone colorectal surgery in the Department of Coloproctological Surgery between November 2014 and March 2016, 16 patients who developed SSIs and could be allocated a diagnosis procedure combination code were selected as SSI cases. Individual SSI cases were matched to non-SSI cases based on a combination of surgical category, age band, sex, wound class, presence of stoma and risk index. Median length of stay (LOS) and piecework reference cost were compared between SSI episodes and non-SSI episodes. FINDINGS: The median LOS for patients with SSI and without SSI was 25.5 [interquartile range (IQR) 21.5-39.3] and 16.5 (IQR 12.5-18.5) days, respectively (P<0.01). The median piecework reference cost for patients with SSI and without SSI was ¥842,155 (IQR ¥716,423-1,388,968) and ¥575,795 (IQR ¥529,638-680,105), respectively (P<0.01). CONCLUSION: SSIs led to a significant increase in LOS and economic burden. Although the SSI episodes appear to be more profitable than the non-SSI episodes, the economic profit for SSI episodes was less than that for non-SSI episodes in the observation period, when opportunity costs were taken into account.

Clinical usefulness of concentrated ascites reinfusion therapy (CART) for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis.

PURPOSE: Cell-free and concentrated ascites reinfusion therapy (CART) is intended to treat patients by ultrafiltration and reinfusion of their refractory ascites. In the CART system, bacteria and cancer cells in removed massive ascites are filtrated. Then, water is removed in the condenser, resulting in a higher protein concentration. The purpose of this study was to assess the clinical usefulness of CART in the treatment of refractory massive ascites in patients with cancerous peritonitis. MATERIALS AND METHODS: CART was performed 13 times in four patients with ovarian and endometrial cancer. RESULTS: Autologous protein with a higher concentration was intravenously administered. The amount of aspirated and condensed ascites was 3,190 +/- 1,086 ml (975 4,500 ml) and 538 +/- 249 ml (100 - 860 ml), respectively. Condensed albumin, albumin concentration, and concentration time were 43.2 +/- 25.8 g, 8.2 +/- 3.3 g/dl, and 73.3 +/- 24.8 min (28 - 122 min), respectively. CART was effective in maintaining serum albumin concentrations, and it is possible to repeat infusion. During CART, patients performance status was 1-2 and vital signs were stable except for mild elevations in body temperature. Daily life was maintained without serious side-effects. CONCLUSIONS: The use of CART for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis contributes to improvements in quality of life and relief of symptoms. With autologous infusion of condensed ascites, patients can avoid infection, allergic reactions, and administration of expensive blood products.

Current role of hybrid CT/angiography system compared with C-arm cone beam CT for interventional oncology.

Hybrid CT/angiography (angiography) system and C-arm cone beam CT provide cross-sectional imaging as an adjunct to angiography. Current interventional oncological procedures can be conducted precisely using these two technologies. In this article, several cases using a hybrid CT/angiography system are shown first, and then the advantages and disadvantages of the hybrid CT/angiography and C-arm cone beam CT are discussed with literature reviews.

Individual differences in prothrombin time-international normalized ratio variation following coadministration of the anticancer agents S-1 and warfarin: 3 case reports.

OBJECTIVE: We report three cases of elevated prothrombin time-international normalized ratios (PT-INR) following the initiation of coadministration of warfarin and S-1, a preparation containing tegafur (FT), gimeracil (CDHP), and oteracil potassium (Oxo). CASE SUMMARIES: The three cases included 2 men and 1 woman aged 79, 71, and 54 y, respectively. PT-INRs were in the range of 2.0 - 3.0 before therapy but were elevated to values in the range of 3.79 - 4.92 within 8 - 17 days after initiating the coadministration of warfarin (1.5 - 3.5 mg/d) and S-1 (80 - 120 mg/d). When the drug interactions in Cases 1 - 3 were evaluated using the Drug Interaction Probability Scale, each of these cases was assessed as "probable". DISCUSSION: The drug interaction between warfarin and S-1 presumably leads to elevated PT-INR because the 5-fluorouracil (5-FU), which is metabolite of FT in S-1, inhibits the metabolic processing of S-warfarin by cytochrome P450 (CYP) 2C9. However, individual differences in the metabolic production of 5-FU from FT because of genetic polymorphisms in CYP2A6 and individual variation in the levels of renal function may lead to complications when 5-FU is coadministered with warfarin as compared to when 5-FU is administered alone. CONCLUSION: It is essential that the dosage level of warfarin is appropriately adjusted by frequent PT-INR measurements when warfarin and S-1 are coadministered.

Outcomes and predictive factors for biochemical relapse following primary androgen deprivation therapy in men with bone scan negative prostate cancer.

PURPOSE: Primary androgen deprivation therapy (PADT) is an important treatment modality for men with localized or locally advanced prostate cancer and without bone metastasis. There is, however, a lack of data on the biochemical relapse (BR) outcomes in these patients. Here, we studied the outcome of a contemporary series of men treated by PADT and investigated predictive risk factors for BR. METHODS: One hundred and fifty-five patients treated by PADT formed the initial study cohort, and BR outcomes in this group were reviewed. The outcomes of men with bone scan negative disease were specifically analysed. The predictive value of a panel of clinical risk factors for BR was evaluated using univariate and multivariate analysis. The results were further validated in a separate cohort of patients without bone metastasis from a second institution (n = 84). RESULTS: Median follow-up was 70 months. In the first study cohort, 109/155 men (70%) had bone scan negative disease. In these patients, only 45% developed BR during the follow-up period with only 28% relapsing within 5 years of initiating PADT. Key-independent factors predicting BR were a high PSA nadir (p = 0.001) and a shorter time to nadir (p < 0.001). A nadir of ≤0.1 ng/ml and time to nadir of >24 months specifically identified men with a very good outcome from PADT. In a second-independent cohort, very similar overall and 5-year BR rates were observed in men without bone metastasis (39 and 35%, respectively). PSA nadir thresholds identified in the first cohort were again able to define a good prognostic group in this re-test cohort (p = 0.005 and p = 0.01, respectively). CONCLUSION: Men treated by PADT and without bone metastasis can have very durable responses to PADT with the majority remaining BR free at 5 years. PSA nadir and time to nadir are key predictors of a good outcome in this group.

Apple pectin affects the efficacy of epigallocatechin gallate on oral sucrose tolerance test in adult mice.

Epigallocatechin gallate (EGCg), a dietary polyphenol and a major tea catechin, is a known sucrase inhibitor. Since dietary pectin is known to modulate some of the functions of the gastrointestinal tract, we investigated whether it could specifically affect the efficacy of EGCg on an oral sucrose tolerance test in mice. Male Crj:CD-1 (ICR) mice (seven weeks old) were randomly divided into two groups and fed a 5 % apple pectin (PE) or 5 % cellulose (CE) diet (control diet) for 28 days. After the experimental diet period, all mice were fasted overnight. A volume of 0.2 mL EGCg (20 mg/mL) was orally administered to all the mice by stainless steel feeding needle via injection syringe and a sucrose tolerance test was performed. The blood glucose levels were measured in blood collected from the tail vein using the OneTouch® Ultra® blood glucose monitoring system. Blood glucose levels at 30 minutes and 60 minutes after sucrose loading in the PE group were significantly higher than initial blood glucose levels. However, blood glucose levels at 30 minutes, 60 minutes, and 120 minutes after sucrose loading in the CE group were not significantly higher than initial blood glucose levels. After laparotomy, plasma lipids were also measured. Plasma triglyceride concentrations were significantly greater in the PE group than in the CE (control) group. This demonstrates that dietary pectin can affect the efficacy of EGCg on the oral sucrose tolerance test in mice.

[Embolization of high flow arteriovenous malformations with HepaSphere microspheres].

OBJECTIVE: To determine the effect, safety, and feasibility of embolization of high flow arteriovenous malformations (AVMs) with HepaSphere microspheres. METHODS: HepaSphere particles swell by absorbing fluids and become soft and deformable with a precisely calibrated diameter. 13 patients with AVMs were treated by transarterial embolization with HepaSphere particles. 3 cases underwent a following AVMs resection surgery. The follow-up period was 3 months to 3 years. Symptoms improvement and image examination were studied. RESULTS: 28 transarterial embolizations were performed in 13 cases. The resection operation was performed in 3 cases after transarterial embolizations. The symptoms in diffused AVMs improved after several transarterial embolizations. Histologically, HepaSphere particles penetrated into the intralesional vessels and conformed to the vessel lumen, resulting in vessel occlusion. Minimal perivascular reaction was observed. CONCLUSIONS: Embolization of high flow AVMs with HepaSphere microspheres is safe and effective. Combined treatment is necessary for diffuse AVMs.

Macular microcirculation and macular oedema in branch retinal vein occlusion.

BACKGROUND/AIMS: The relationship between the blood-flow velocity in the perifoveal capillaries and macular oedema was investigated in patients with branch retinal vein occlusion (BRVO). METHODS: This study compared 18 patients with BRVO and 16 healthy volunteers. Perifoveal capillary blood-flow velocity was measured on fluorescein angiograms with a scanning laser ophthalmoscope by the tracing method. Retinal thickness at the central fovea was measured by optical coherence tomography. Then, the relation between perifoveal capillary blood-flow velocity and retinal thickness at the central fovea was investigated. RESULTS: Perifoveal capillary blood-flow velocity was significantly lower in the patients with BRVO (1.08 (SD 0.28) mm/s) than in the healthy volunteers (1.49 (0.11) mm/s) (p<0.0001). Capillary blood-flow velocity showed a negative correlation with the retinal thickness at the central fovea in the two groups (r = -0.8426, p<0.0001). Multivariate linear regression analysis with stepwise variable selection confirmed that capillary blood-flow velocity was an independent determinant of the retinal thickness at the central fovea (p<0.001). CONCLUSION: A reduction in perifoveal capillary blood-flow velocity may be involved in the development of macular oedema in patients with BRVO.

Tentorial incision in a lateral-medial direction with minimal retraction of the temporal lobe in the subtemporal transtentorial approach to the middle tentorial incisural space.

OBJECTIVE: The subtemporal transtentorial approach provides excellent exposure of the middle incisural space. A modification of the subtemporal transtentorial approach with use of a partial mastoidectomy is presented to avoid damage to the temporal lobe as a result of retraction as well as damage to venous structures. METHODS: Four patients, one with a superior cerebellar artery aneurysm, one with a metastatic tumor in the midbrain, one with a tentorial meningioma, and one with a tentorial schwannoma were treated with the present approach. After subtemporal craniotomy, all of the cortical bone overlying the mastoid was removed. The mastoid air cells were drilled down, and the upper part of Trautman's triangle was exposed above the level of the lateral semicircular canal. The presigmoid dura and the temporal dura were opened and connected by incising the superior petrosal sinus. The cerebellar tentorium was incised in a lateral-medial direction along the angle of the tentorium. RESULTS: In each case, the tentorium was incised with minimal retraction of the temporal lobe without any damage to the temporal lobe, or venous structures. The present approach yielded excellent visualization of the lesion and adjacent neurovascular structures. In 3 of 4 cases, the lesions were successfully treated. In the patient with a tentorial schwannoma extending from the middle to posterior incisural space, the extreme lateral supracerebellar-infratentorial approach was combined with the present approach. CONCLUSIONS: Although additional partial mastoidectomy is time-consuming, it reduces the risk of damage to the temporal lobe as a result of retraction as well as damage to venous structures.

Changes of vascular endothelial growth factor after vitrectomy for macular edema secondary to retinal vein occlusion.

PURPOSE: To examine whether vitrectomy combined with retinal photocoagulation reduces the vitreous level of vascular endothelial growth factor (VEGF) in patients with macular edema associated with retinal vein occlusion (RVO). METHODS: The authors measured VEGF levels in vitreous samples from four eyes of four patients with RVO during vitrectomy and fluid samples obtained during revitrectomy 3 to 9 months postoperatively for complications: an epiretinal membrane in two patients, macular holes in one patient, and vitreous hemorrhage in one patient. During vitrectomy, retinal photocoagulation was performed on the ischemic region of the retina in all cases (mean of 510 shots). RESULTS: In four eyes with RVO, there was a difference in the vitreous VEGF levels between the vitreous samples obtained during vitrectomy (mean of 2692 pg/mL, range of 15.6-9040 pg/mL) and the fluid samples obtained at the time of revitrectomy (mean of 947 pg/mL, range of 15.6-3430 pg/mL). CONCLUSIONS: The results suggest that the vitreous levels of VEGF may be reduced by vitrectomy combined with retinal photocoagulation for macular edema with RVO. It may be important to reduce the vitreous levels of VEGF by vitrectomy and retinal photocoagulation for ischemic retina in macular edema with RVO.

Helicobacter pylori eradication reduced the incidence of gastric cancer, especially of the intestinal type.

BACKGROUND: Although Helicobacter pylori infection is closely associated with gastric cancer development, follow-up studies after H. pylori eradication are still scarce. AIM: To clarify the cancer preventive effect of H. pylori eradication, with special attention to differences in effect according to histology. METHODS: Patients who underwent H. pylori eradication therapy and were followed-up endoscopically for at least 1 year were analysed. The incidence of gastric cancer and factors associated with cancer development were investigated. RESULTS: A total of 1807 patients were enrolled. Six of 1519 H. pylori eradicated and five of 288 persistent subjects developed gastric cancer. Four of the eradicated subjects developed the intestinal type and two the diffuse type, while four of the persistent subjects developed the intestinal type and one the diffuse type. Kaplan-Meier analysis indicated a significantly lower incidence in eradicated patients than in persistent patients. The incidence of intestinal type was significantly lower than in eradicated patients, while the diffuse type could not be evaluated because of the low incidence. CONCLUSIONS: Helicobacter pylori-eradicated patients had a reduced incidence of gastric cancer compared with H. pylori-persistent patients, particularly the intestinal type, suggesting that H. pylori is strongly associated with intestinal-type gastric cancer.

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines.

AIM: To ascertain whether vitreous and plasma levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and fundus findings could predict the outcome of vitreous surgery in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluid samples were obtained during vitreoretinal surgery from 73 consecutive eyes with PDR. The levels of VEGF and IL-6 in vitreous fluid and plasma were determined by enzyme-linked immunosorbent assay. Patients were prospectively followed for 6 months and the postoperative outcome was analysed by logistic regression analysis. RESULTS: No improvement and/or progression of PDR occurred in 23 (32%) of the 73 eyes (progression group). The vitreous levels of VEGF and IL-6 were significantly higher in eyes from the progression group than in eyes with regression of PDR (regression group) (P=0.0032 and 0.0088, respectively). Multivariate logistic regression analysis showed that higher vitreous levels of VEGF were associated with the progression of PDR after vitreous surgery (odds ratio 2.72, P=0.0003). CONCLUSIONS: High vitreous levels of VEGF identified as a significant risk factor for the outcome of vitreous surgery in patients with PDR. A model was developed to predict the probability of PDR progression and measurement of the vitreous level of VEGF may be useful for predicting the outcome of surgery.

Darbepoetin alfa (Aranesp) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults.

Recognition memory was assessed in adult rats that received bilateral injections of saline (sham lesions) or ibotenic acid (lesioned) in the ventral hippocampus as neonates (postnatal day 7, PD7) or young adult (42 days of age, PD42) using the Novel Object Recognition Test (NORT). Normal or sham-lesioned rats were able to distinguish novel from familiar objects over a 0.5 and 2 h delay between the sample and choice phases. Adult rats (PD70) lesioned as neonates performed progressively worse than sham-lesioned animals at delays of 0.5 and 2 h. A single injection of darbepoetin alfa (500 or 5000 U/kg, i.p.), given 1 h before the sample phase restored performance 0.5 or 2 h later in the choice phase to same levels as sham-lesioned rats. Adults lesioned on PD42 displayed deficits in NORT performance with a 2 h delay between the choice and sample phases that were completely reversed by administration of darbepoetin alfa (5000 U/kg, i.p.) 1 h before the sample phase. These results suggest that darbepoetin alfa may have utility in treating memory deficits associated with brain dysfunction related to developmental disorders such as schizophrenia.

Risk evaluation of outcome of vitreous surgery for proliferative diabetic retinopathy based on vitreous level of vascular endothelial growth factor and angiotensin II.

AIMS: To ascertain whether measurement of the vitreous fluid levels of vascular endothelial growth factor (VEGF) or angiotensin II (Ang II) could predict the outcome of vitreous surgery in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective observational case study was performed in 61 consecutive patients (61 eyes) with PDR who underwent vitreoretinal surgery. Vitreous fluid samples were obtained during surgery. The VEGF level in vitreous fluid and plasma was determined by enzyme linked immunosorbent assay, while the Ang II level was measured by radioimmunoassay. Patients were prospectively followed for 6 months and the postoperative outcome was analysed by logistic regression analysis. RESULTS: No improvement and/or progression of PDR was seen in 15 (25%) of the 61 eyes. Vitreous levels of VEGF and Ang II were significantly higher in eyes with progression of PDR than in eyes with regression of PDR (p = 0.0044, and p = 0.0178, respectively). Multivariate logistic regression analysis showed that the vitreous VEGF level increased along with the progression of PDR after vitreous surgery (odds ratio 2.48, p = 0.0008). CONCLUSION: A high vitreous fluid VEGF level is associated with a significant risk of postoperative progression of PDR. The vitreous level of VEGF at the time of surgery may be a useful predictor of the outcome.

[3H]alpha,beta-methylene ATP binding to P2X purinoceptor is unaffected by volatile anaesthetics.

BACKGROUND AND OBJECTIVE: The P2X receptor is responsible for fast excitatory neurotransmission in the central nervous system. This receptor is suggested as one of the targets of volatile anaesthetics. The study was undertaken to examine the site of action of volatile anaesthetics, especially for P2X purinoceptor-mediated neurotransmission. METHODS: The effect of sevoflurane and isoflurane on [3H]alpha,beta-methylene ATP binding was investigated in rat crude synaptic membranes. The crude synaptic membranes were prepared from Sprague-Dawley rat brains by centrifugation and then incubated with volatile anaesthetics or P2 receptor antagonists. RESULTS: [3H]alpha,beta-methylene ATP binding was unchanged by either sevoflurane or isoflurane at clinically relevant concentrations. Suramin, a P2 antagonist, significantly (P < 0.05) decreased the binding of [3H]alpha,beta-methylene ATP in a dose-dependent manner (68.7 +/- 14.7% at 10 micromol, 49.5 +/- 6.4% at 50 micromol, 24.3 +/- 5.7% at 100 micromol, n = 10, mean +/- SD), whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), another P2 antagonist, did not affect the binding. CONCLUSIONS: The suppressive effect of volatile anaesthetics on ATP-mediated excitatory synaptic transmission could be one site of action. However, the blockade of ATP binding to P2X receptors is not a mechanism of action of volatile anaesthetics.

Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine.

Clinical application of anticancer agents has been often hampered by toxicity against normal cells, so the achievement of their cancer-specific action is still one of the major challenges to be addressed. Previously, we reported that arsenic trioxide (As2O3) could be a promising new drug against not only leukemia but also solid tumors. The cytotoxicity of As2O3 occurred through the generation of reactive oxygen species (ROS), thus inhibiting radical scavenging systems would enhance the therapeutic efficacy of As2O3 provided that normal cells were relatively resistant to such a measure. Here, we report that the combination therapy of As2O3 with L-buthionine-sulfoximine (BSO), which inhibits a critical step in glutathione synthesis, effectively enhanced in vitro growth inhibition effect of As2O3 on all 11 investigated cell lines arising from prostate, breast, lung, colon, cervix, bladder, and kidney cancers, compared with As2O3 treatment alone. Furthermore, this combination enhanced cytotoxicity to cell lines from prostate cancer with less toxicity to those from normal prostate. In vitro cytotoxic assay using ROS-related compounds demonstrated that hydrogen peroxide (H2O2) is a major cytotoxic mediator among ROS molecules. Biochemical analysis showed that combined use of As2O3 and BSO blocked H2O2-scavenging systems including glutathione, catalase, and glutathione peroxidase, and that the degree of this blockade was well correlated with intracellular ROS levels and sensitivity to this treatment. Finally, the effectiveness of the combination therapy of As2O3 with BSO was demonstrated with an orthotopic model of prostate cancer metastasis. We propose that the combination therapy of As2O3 with BSO is a valid means of blockade of H2O2-scavenging system, and that the combination of a ROS-generating agent with an inhibitor of major scavenging systems is effective in terms of both efficacy and selectivity. Furthermore, because the effective doses of both compounds are within clinically achievable range, this report will lead to immediate benefit for the development of a new cancer therapy.