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Purpose Postmastectomy radiation therapy is an important component of the multimodality approach to later-stage breast cancers. Unfortunately, despite its proven survival benefits, postmastectomy radiation therapy is deleterious to the skin and soft tissue, causing increased complications and worse aesthetic outcomes after breast reconstruction.There is currently no effective pharmaceutical agent to mitigate the soft tissue fibrosis and hypovascularity associated with soft tissue radiation. We hypothesized that a novel topical formulation of deferoxamine (DFX) will result in improved cutaneous vascularity and soft tissue pliability in an animal model of irradiated tissue expander-based breast reconstruction. Methods This study consisted of 16 hairless rats divided into 4 equal groups: a control group (expander only), a tissue expanded and irradiated group, a tissue expanded + DFX group, and a tissue expanded/irradiated/DFX group. A novel topical formulation of DFX consisted of reconstituted drug dissolved in agents designed to enhance dermal penetrance. Vessels per high-power field (vHPF) were quantified histologically; micro-computed tomography angiography was used to assess vessel volume fraction (VVF) and vessel length density. Results Irradiated skin had less vascularity compared with control (3.81 vHPF vs 8.25 vHPF, P = 0.03; 0.79% VVF vs 1.53% VVF, P = 0.06). Treatment of irradiated skin with topical DFX reversed these effects, resulting in vascular findings similar to the control group histologically (7.94 vHPF vs 8.25 HPF, P = 0.985) and via micro-computed tomography angiography (1.05% VVF vs 1.53% VVF, P = 0.272). Similarly, radiation resulted in less volume expansion compared with controls (0.72 vs 0.8 mL, P = 0.04), whereas treatment with topical DFX reversed this effect, allowing for an expansion volume similar to the control group (0.81 vs 0.80 mL, P = 0.999). Conclusions In an animal model of irradiated tissue expander-based breast reconstruction, treatment with topical DFX improved the cutaneous vascularity and tissue pliability, resulting in vascular density and final tissue expansion volumes similar to those found in the nonirradiated control group. Topical DFX may be an effective agent for the treatment of soft tissue radiation injury; future studies are indicated to further characterize this novel drug formulation.

Aim To profile molecular changes in lipopolysaccharide (LPS)‐induced experimental pulpitis in a rat model and explore the feasibility of a molecular‐based diagnostic strategy for pulpitis. Methodology Seventy‐three maxillary incisors of Sprague‐Dawley rats were used to establish pulpitis models with LPS. Inflammatory grading was performed in four equal sections of the pulp divided from the injured site to the root apex. An antibody array was used to compare the expression of 67 molecules between control pulp and inflamed pulp 12 and 72 h after LPS application. The levels of differentially expressed molecules in the control and inflamed pulp (collected at 3, 6, 9, 12, 24 and 72 h after LPS treatment) were examined via ELISA, and correlations between inflammatory scores and molecule expression were assessed. The molecule distributions in the pulp were investigated by immunofluorescence staining. Data were analysed with paired t‐test, one‐way anova, Kruskal–Wallis tests, and Spearman’s and Pearson’s correlations with significance set at P

Adipocyte sizes from adipose tissue of mature animals form a bimodal distribution, thus reporting mean cell size is misleading. The objectives of this study were to develop a robust method for testing bimodality of porcine adipocytes, describe the size distribution with an informative metric, and statistically test hypertrophy and appearance of new small adipocytes, possibly resulting from hyperplasia or lipid filling of previously divided fibroblastic cells. Ninety-three percent of adipose samples measured were bimodal (P < 0.0001); therefore, we describe and propose a method of testing hyperplasia or lipid filling of previously divided fibroblastic cells based upon the probability of an adipocyte falling into 2 chosen competing “bins” as adiposity increases. We also conclude that increased adiposity is correlated positively with an adipocyte being found in the minor mode (r = 0.46) and correlated negatively with an adipocyte being found in the major mode (r = −0.22), providing evidence of either hyperplasia or lipid filling of previously divided fibroblastic cells. We additionally conclude that as adiposity increases, the mode of the major distribution of cells occurs at a larger diameter of adipocyte, indicating hypertrophy.

To analyze clinical feature and evaluate long-term outcome of patients with thallium poisoning.An observational series of cases with acute thallium poisoning was analyzed retrospectively in West China Hospital of Sichuan University between 2000 and 2010. The clinical data including symptom, determination of thallium level, treatment, neurophysiological examination, and neuropsychological evaluation were analyzed. The patients were followed up until December 2012.Seven men and six women were enrolled in the study. The median patient age was 37 years (range: 15-53 years). The median duration of hospitalization was 44 days (range: 7-72). All the patients were misdiagnosed initially. One patient died in the hospital. The other 12 patients were followed for a median of 7 years (range: 1-12 years) after discharge from hospital. One patient died from leukemia in the first year of follow-up. Long-term outcome results showed peripheral neuropathy improved substantially. However, many patients have mild or moderate sequelae in sensory nerve fibers of distal lower extremity. A sural nerve biopsy in one patient revealed shrunken axons, distorted myelin sheath, and myelinated fibers loss. During follow-up period, problem of intelligence (4/12 patients, 33%), memory impairment (4/12, 33%), anxiety (6/12, 50%), and depression (5/12, 42%) were demonstrated.Neurological symptoms may lead to misdiagnosis of thallium poisoning. Mild or moderate neurological sequelae may last for a long time after thallium poisoning.

Background/Aims: Somatostatin is regarded as a prophylactic agent on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), but studies are still controversial. Materials and Methods: Electronic databases, including PubMed, EMBASE, the Cochrane library, and the Science Citation Index, were searched to retrieve relevant trials. In addition, meeting abstracts and the reference lists of retrieved articles were reviewed for further relevant studies. Results: Eleven randomized controlled trials (RCTs), enrolling a total of 2869 patients, were included in the meta-analysis. After data were pooled from somatostatin trials, PEP occurred in 8.36% of controls versus 5.62% of the treated group, with a slight significance [relative risk (RR) =0.58, 95% confidence interval (CI) 0.35–0.98, P = 0.04]. The funnel plot showed no asymmetry with a negative slope (P = 0.108). The meta-analysis produced negative results for short-term infusion of somatostatin (RR = 1.40, 95% CI 0.93–2.12, P = 0.11), whereas a bolus or long-term injection of the drug proved effective (RR = 0.25, 95% CI 0.13–0.47, P < 0.0001; RR = 0.44, 95% CI 0.27–0.71, P = 0.0008). Postprocedure hyperamylasemia and pain was also observed in the meta-analysis, the pooled RR was significant for reduced risk of postprocedure hyperamylasemia (RR = 0.72, 95%CI 0.63 to 0.81, P < 0.00001), but not for the pain (RR = 0.67, 95% CI 0.42 to 1.08, P = 0.10). Conclusion: The current meta-analysis on the prophylactic use of somatostatin in patients undergoing ERCP documents a lack of benefit when given as short-term infusion, but showed an advantage of a single bolus or long-term injection. The beneficial effect of somatostatin, in reducing the incidence of postprocedural hyperamylasemia seems of marginal clinical significance. However, more new confirmatory data are needed to settle residual doubts.

Clinical data suggest that large radiation fractions are biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an appealing delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife to deliver a hypofractionated stereotactic body radiation therapy (SBRT) boost to patients with intermediate- to high-risk prostate cancer. Twenty-four patients were treated with hypofractionated SBRT and supplemental external radiation therapy plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were collected with American Urological Association (AUA) symptom score and Expanded Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment. PSA responses were monitored; acute urinary and rectal toxicities were assessed using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned treatment with an average follow-up of 9.3 months. For patients who did not receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects associated with treatment included Grade 2 urinary and gastrointestinal toxicity but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores returned to baseline by six months post-treatment. Hypofractionated SBRT combined with IMRT offers radiobiological benefits of a large fraction boost for dose escalation and is a well tolerated treatment option for men with intermediate- to high-risk prostate cancer. Early results are encouraging with biochemical response and acceptable toxicity. These data provide a basis for the design of a phase II clinical trial.

The p16(INK4a) gene is a cell cycle inhibitor and a major tumour suppressor protein, but the regulation and effects on tumour cells' invasion process of p16(INK4a) is poorly known. A role for p16(INK4a) in basal cell carcinoma is suggested by the observation that p16(INK4a) was upregulated at the invasive front of the majority of basal cell carcinomas with infiltrative growth patterns, accompanied by cessation of proliferation. In this paper, we explore whether there is a difference of tumour cells' proliferative activity between the centre and the invasion front tissues of human colorectal cancer and its relationship with the expression and methylation status of p16(INK4a) gene. We obtained the centre and the invasion front tissues of colorectal cancer respectively by the technology of laser mircodissection. The expressions of the proliferating cell nuclear antigen ki67 and p16(INK4a) were assessed by immunohistochemistry, methylation-specific polymerase chain reaction (MS-PCR) and reverse-transcription polymerase chain reaction (RT-PCR) in the different areas. There was a significant difference in the expressions of ki67 between the centre and the invasion front tissues (p < 0.05). The difference did not correlate with age, sex, Dukes stage but did correlate with expression of p16(INK4a) gene (chi(2) = 25.37, p < 0.01). Furthermore, hypermethylation of the promoter was the major mechanism of inactivation of p16(INK4a) in the centre areas. Demethylation of the p16(INK4a) promoter, the elevated expression of p16(INK4a) protein and mRNA level was proved in the invasion front. Our finding suggested that enhanced invasion in tumours was accompanied by ceased proliferation in the invasion fronts of human colorectal cancer. This interesting phenomenon may be due to not only the microenvironment, but also the molecular changes such as p16(INK4a) status.

The main source of fat in the diet in rural areas of northern China is soybean oil, therefore the pattern of essential fatty acids in human milk may be assumed to differ from that in milk from women in Western countries and to be similar to that of vegans. The concentrations of long chain polyunsaturated fatty acids in human milk and information on diet were analysed for 41 lactating women in rural areas of north China, and the growth of their infants was measured. The subjects were divided into two groups (group I, 1 mo postpartum; group II, 3 mo postpartum). The dietary intake of the mothers was high in carbohydrate and low in fat, protein and energy. The concentrations of linoleic acid (LA) and alpha-linolenic acid (LNA) were high. The ratio of LA to LNA, (21.6), was higher than has been reported from other countries. The concentration of docosa-hexaenoic acid (DHA) was low and the ratio of arachidonic acid (AA) to DHA was much higher (2.8) than recommended and similar to that found in vegans. The concentrations of AA and DHA in the milk correlated positively with the infants' weight gain at the third month (p

The metabolic consequences of heat stress (HS) are atypical (i.e. hyperinsulinemia) considering the animal's nutritional status and a compromised intestinal barrier may initiate the pathophysiologi...

A 17-year-old boy with juvenile rheumatoid arthritis presented with jaundice, confusion, hemolytic anemia, thrombocytopenia, and acute renal failure secondary to titer-confirmed acute Epstein-Barr virus (EBV). Renal biopsy specimen revealed interstitial nephritis with an inflammatory infiltrate composed of cytotoxic/suppressor T cells, and interstitial mononuclear cell nuclei expressed EBV encoded RNA-1 (EBER-1) mRNA. Methylprednisolone treatment resulted in rapid improvement.

The study investigated the role of androgen receptor (AR) as a potential target for the treatment of bladder cancer in regulating epithelial-mesenchymal transition or transformation (EMT). Cell proliferation, and migration capacity were determined in bladder cancer T24 cells treated with small interfering RNA directed against AR, and expression levels of E-cadherin, β-catenin and N- cadherin were assessed using quantitative reverse transcription PCR (qRT-PCR). Tumour cell growth was evaluated in vivo in T24 tumour-bearing nude mice receiving electroporation-assisted administration of anti-AR small interfering RNA. It was found that low AR expression decreased proliferation and migration of bladder cancer cells. In vivo experiments showed that silencing AR expression significantly suppressed AR-positive bladder tumour growth with decreased cell proliferation. Low AR level of T24 bladder cancer cells treated with dehydrotestosterone (DHT) decreased expression of E-cadherin, β-catenin and N-cadherin expression, indicating a strong sensitivity to the EMT and In cells with low AR content, TGF-β induced down-regulation of E-cadherin and β-catenin. It is concluded that suppression of AR expression decreased the production of TGF-β, inhibiting EMT and bladder cancer cell growth in vitro and in vivo, implying that its use might be a potential therapeutic target for the treatment of bladder cancer.

To observe the effects of supplemental dietary d-α-tocopherol in relation to dietary energy on growth and immune status in dairy calves, 32 newborn Holstein bull calves were assigned to 1 of 4 treatments for 5 wk in a 2 × 2 factorial, randomized complete block, split-plot design. Calves received moderate growth (MG) or low growth (LG) all-milk dietary treatments, formulated to support daily gains of 0.5 or 0.25 kg/d, respectively, per the dietary energy recommendation for milk-fed calves according to the National Research Council's Nutrient Requirements of Dairy Cattle. Calves in both groups were either injected i.m. with Vital E-A+D (injectable solution of vitamins E, A, and D) on d 1 and supplemented with Emcelle Tocopherol (micellized vitamin E) via milk daily (MG-S and LG-S), or were not supplemented (MG-C and LG-C) during the study period. Total weight gain of MG calves was greater than that of LG calves and tended to be greater in MG-S calves than in MG-C calves. Calves receiving vitamin supplementation demonstrated greater concentrations of plasma α-tocopherol, retinol, and 25-(OH)-vitamin D than did control calves, whereas MG calves demonstrated a lower concentration of plasma α-tocopherol than did LG calves. The apparent increased utilization of α-tocopherol by MG calves was accompanied by a rise in serum haptoglobin, a positive acute-phase protein and indicator of inflammation, especially in MG-C calves. Serum amyloid A, also a positive acute-phase protein, was not different among groups, but was elevated from baseline in all groups during wk 1 through 3. Plasma IgG1 concentrations were higher in MG-S and LG-S calves than in their nonsupplemented dietary counterparts, whereas plasma IgG2, IgA, and IgM concentrations were not different among groups. In summary, dietary supplementation of d-α-tocopherol improved plasma α-tocopherol status and tended to increase growth in calves fed for 0.5 kg of average daily gain. Vitamin supplementation ameliorated the rise of serum haptoglobin associated with acute inflammation in MG calves, and may have improved passive transfer of maternal antibody. These results indicate a role for α-tocopherol in prevention of proinflammatory state associated with greater dietary energy and onset of infectious disease.

1 Although it well established that corticotropin-releasing factor (CRF) injected i.v. can cause hypotension and vasodilatation, there is no in vitro evidence that CRF acts as a vasodilator. We have therefore tested the hypothesis that the hypotensive effect of i.v. CRF is due to a direct vasodilator action by carrying out experiments in vitro on rat resistance arteries (i.d. 150–300 μm). 2 Initial in vivo experiments confirmed that CRF (1.5 nmol kg−1) injected i.v. caused hypotension in rats, this being partially antagonized by the CRF analogue CRF9–41. 3 For the in vitro experiments, vessels were taken from the mesenteric, cerebral and femoral vascular beds, and mounted as ring preparations in an isometric myograph. The vessels were pre-contracted with one of 3 agonists (prostaglandin F2α, arginine vasopressin or noradrenaline) or with a high-potassium solution (K+). 4 With maximal concentrations of the agonists, CRF caused relaxation of mesenteric and cerebral vessels with 10 nm, and near complete relaxation with 100 nm. Femoral vessels preconstricted with agonists and all vessels preconstricted with K+ were less affected by CRF. In the mesenteric vessels, with sub-maximal levels of pre-constriction, CRF caused substantial relaxation at 1 nm and could cause complete relaxation at 10 nm. 5 The relaxant effect of CRF on contractions of mesenteric vessels was antagonized by 100 nm CRF9–41. Neither tetraethyl ammonium (30 mm) nor glibenclamide (3 μm) antagonized the relaxant effect of CRF. 6 The relaxant effect of CRF on mesenteric small arteries was found to be unaffected by removal of the endothelium. 7 The results indicate that CRF causes an endothelial-independent vasodilatation of rat resistance arteries under in vitro conditions at concentrations which are consistent with this being an important cause of the hypotension observed with i.v. injection of CRF.

Background: Proctitis following prostate cancer radiation therapy is a primary determinant of quality of life (QOL). While previous studies have assessed acute rectal morbidity at 1 month after stereotactic body radiotherapy (SBRT), little data exist on the prevalence and severity of rectal morbidity within the first week following treatment. This study reports the acute bowel morbidity one week following prostate SBRT. Materials and methods: Between May 2013 and August 2014, 103 patients with clinically localized prostate cancer were treated with 35 to 36.25 Gy in five fractions using robotic SBRT delivered on a prospective clinical trial. Bowel toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv.4). Bowel QOL was assessed using EPIC-26 questionnaire bowel domain at baseline, one week, one month, and three months. Time-dependent changes in bowel symptoms were statistically compared using the Wilcoxon signed-rank test. Clinically significant change was assessed by the minimally important difference (MID) in EPIC score. This was defined as a change of one-half standard deviation (SD) from the baseline score. Results: One hundred and three patients with a minimum of three months of follow-up were analyzed. The cumulative incidence of acute grade 2 GI toxicity was 23%. There were no acute ≥ grade 3 bowel toxicities. EPIC bowel summary scores maximally declined at 1 week after SBRT (-13.9, p

Background The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism. Methods Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires. Results All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment. Conclusions Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.

We describe the first histopathologic analysis of prostatic tissue following hypofractionated robotic radiation therapy. A 66 year-old man presented with stage II, low risk adenocarcinoma of the prostate and underwent elective conformal hypofractionated radiation therapy. His pretreatment evaluation revealed T1c adenocarcinoma, Gleason's grade 3 + 3 = 6 and a prostate specific antigen (PSA) level of 4.87 ng/ml. Hypofractionated radiation therapy (37.5 Gy in five daily fractions of 7.5 Gy) was completed on an Internal Review Board approved protocol. One year later, he developed progressive urinary retention. Transurethral prostatic resection was performed to alleviate obstructive symptoms. Bilobar hypertrophy was observed without evidence of stricture. Histolopathologic analyses of resected prostate tissues revealed changes consistent with radiation treatment, including cellular changes, inflammation, glandular atrophy and hyperplasia. There was no evidence of residual cancer, fibrosis or necrosis. The patient's postoperative course was uneventful with post-treatment PSA of 0.5 ng/ml and residual grade 1 stress incontinence.

Introduction With conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma. Methods Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife® image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide. Results During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients. Conclusion We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.

Nitric oxide (NO), produced in lung vascular endothelium and airway epithelium, has an important role in regulating smooth muscle cell growth and tone. Chronic lung disease, a frequent complication of premature birth, is characterized by excess abundance, tone, and reactivity of smooth muscle in the pulmonary circulation and conducting airways, leading to increased lung vascular and airway resistance. Whether these structural and functional changes are associated with diminished pulmonary expression of endothelial nitric oxide synthase (eNOS) protein is unknown. Both quantitative immunoblot analysis and semiquantitative immunohistochemistry showed that there was less eNOS protein in the endothelium of small intrapulmonary arteries and epithelium of small airways of preterm lambs that were mechanically ventilated for 3 wk compared with control lambs born at term. No significant differences were detected for other proteins (inducible NOS, α-smooth muscle actin, and pancytokeratin). Lung vascular and respiratory tract resistances were greater in the chronically ventilated preterm lambs compared with control term lambs. These results support the notion that decreased eNOS in the pulmonary circulation and respiratory tract of preterm lambs may contribute to the pathophysiology of chronic lung disease.

Purpose: CyberKnife offers the potential benefits of non‐isocentric, non‐coplanar treatment delivery. However, its planning is a laborious manual, trial‐and‐error process. This study is to investigate whether an overlap volume histogram (OVH)‐driven planning approach can produce clinically acceptable plans for treatment of localized prostate cancer. Methods: It is assumed that given consistent target coverage, patients with a relevant target‐organ spatial relationship should have similar organ sparing. The OVH is used to characterize the 3‐D spatial relationship between an organ and a target. A database containing the OVH and DVH of prior plans is built to serve as an external reference. During the initial planning, the OVH is used to search through the database to find a prior patient group whose target‐organ relationship is related to that of a new patient. The planning objectives for the new patient are then estimated from the group and input into the CyberKnife TPS for optimization. To demonstrate the effectiveness of the method, the plans of 12 prostate patients (prescription: 36.25Gy in 5 fractions) are generated by the OVH approach and compared to the corresponding clinical plans using the in‐house dosimetric guidelines. Results: Physicians confirm that OVH plans are clinically acceptable. OVH plans: on average, Vcc(37Gy) and V(18.12Gy) to the bladder decrease 1cc and 6% (p

165 Background: When treating patients with prostate cancer, hypofractionation with SBRT takes advantage of radiobiologically favorable factors as compared to conventional fractionation. However, this may increase the risk of urinary toxicity, especially in patients with prior procedures for BPH. Herein, we report early urinary toxicity following SBRT in patients with a history of procedures for BPH. Methods: Thirty three patients treated with SBRT for localized prostate cancer from February 2009 to October 2011 at Georgetown University Hospital with history of a prior procedure for BPH were included in this retrospective analysis. Treatment was delivered using the CyberKnife with doses of 35 Gy-36.25 Gy in 5 fractions. Toxicities were scored using the CTCAE v.3. Cystoscopy findings were retrospectively reviewed. Patient-reported urinary symptoms were assessed using the American Urological Association Symptom Score (AUA). Results: The median age was 70 years (range, 64 - 84). The median follow-up time was 18.7 months (range 9.2 – 38.9). Grade 2 or 3 urinary toxicity occurred in 9 patients and there were no grade 4 or 5 toxicities. Hematuria occurred in 12 patients. The median time to onset of hematuria from SBRT was 6 months (range 1 – 30). Grade 1 hematuria occurred in 7 patients, grade 2 in 4 patients and 1 patient experienced grade 3. Cystoscopy was performed in 9 of these patients at a median time of 9 months (range 3-27). Eight had hyperemia or evidence of bleeding from the prostatic urethra and 5 of these patients also had evidence of bleeding from the bladder neck/wall. All patients except one, who died from other causes, are still being followed and hematuria has resolved in 9 of the 12 patients. The median baseline AUA symptom score of 7 increased to 11 at 1 month, however decreased to a median score of 6 at 3 months. The median AUA symptom score increased to 9 at 1 year. Conclusions: A history of prior transurethral resection of prostate may predispose patients to increased urinary toxicity and hematuria following prostate SBRT. Stricter urethra/bladder neck dosimetric criteria or alternative fractionation regimens may be required to decrease urinary toxicity in these patients.

e15134 Background: Clinical data suggest that fewer large fractions are radio-biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is the ideal delivery s...

Newly developed substance P (SP) analogs with altered N-terminal sequences which equalize the lipophilicity of the N-terminal and C-terminal elements and of their fusion product were examined using i.t. injection in mice. I.t. injection of either the full length analog or the C-terminal hexapeptide (CP) produced biting and scratching behavior similar to that elicited by SP. SPF was approximately 5-fold and CP 14-fold less potent than native SP. The N-terminal peptide (NP) was inactive by itself but inhibited CP-elicited behavior. Naloxone antagonized this action of NP and shifted the SPF dose-response curve 4-fold to the left. However, naloxone had no effect on the action of CP or on the action of any of the native neurokinins. The results are consistent with the hypothesis that N- and C-terminal analogs of SP can have opioid and SP-like actions, respectively, in the CNS of rodents. Furthermore, analogs of SP which include at least the terminal tetrapeptide retain neurokinin activity.

20735 Background: To explore the effects of Chinese herbal medicine LC07 infusion external treatment on chemotherapy-induced peripheral neuropathy. Methods: We tested LC07 infusion external treatme...