Deep PSA response and extended time-to-nadir as robust predictors of survival in Asian patients with de novo metastatic hormone-sensitive prostate cancer receiving upfront intensified treatment.

INTRODUCTION: In de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real-world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes. METHODS: A prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6-months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders. FINDINGS: A total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression-free survival (HR = 0.56; 95%CI = 0.34-0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26-0.97; p = 0.036), and cancer-specific survival (HR = 0.43; 95%CI = 0.19-0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis. CONCLUSION: Our analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real-world setting, providing valuable information for patient counselling and potentially guiding future trial design.

Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer.

BACKGROUND: Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. METHODS: Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). RESULTS: Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53-0.93], p = .014), pneumonia (adjusted SHR 0.76 [0.59-0.99], p = .040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39-0.79], p = .001), but not urinary tract infection (adjusted SHR 0.91 [0.62-1.35], p = .643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. CONCLUSIONS: Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess.

Monopolar versus bipolar transurethral resection of bladder Tumour: post-hoc analysis of a prospective trial.

INTRODUCTION: Previously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention. METHODS: This is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: From the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433-1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511-2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219-2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564-2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS. CONCLUSION: Despite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.

Adjuvant treatment for renal cell carcinoma: current status and future.

PURPOSE OF REVIEW: Renal cell carcinoma (RCC) is resistant to chemotherapy. Adjuvant interferon and tyrosine kinase inhibitors were ineffective. Immune checkpoint inhibitors (ICIs), however, have shed new hope in this setting. In the current review, updated evidence of adjuvant therapy in RCC is summarized. RECENT FINDINGS: KEYNOTE-564 demonstrated survival benefits of adjuvant Pembrolizumab in RCC. EAU guidelines now recommend adjuvant pembrolizumab to ccRCC patients at an increased risk of recurrence, as defined in the study. At a median follow-up of 24 months, the disease-free survival (DFS) was significantly longer for the Pembrolizumab group than placebo group [DFS 77.3 vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval (95% CI), 0.53-0.87; P = 0.002]. From its updated analysis, at median follow up of 57.2 months, overall survival (OS) benefit of Pembrolizumab was demonstrated (hazard ratio for death, 0.62; 95% CI, 0.44-0.87; P = 0.005). A number of other adjuvant ICI trials have though been negative. SUMMARY: Pembrolizumab is currently the only adjuvant therapy for RCC showing survival benefits, amid a number of negative trials on adjuvant immunotherapy. Currently, there is no role for adjuvant tyrosine-kinase inhibitors and radiotherapy for RCC. Meanwhile, a multidisciplinary approach and shared decision-making should be adopted.

OsUVR8b, rather than OsUVR8a, plays a predominant role in rice UVR8-mediated UV-B response.

UV RESISTANCE LOCUS 8 (UVR8) has been identified in Arabidopsis thaliana as the receptor mediating responses to UV-B radiation. However, UVR8-mediated UV-B signaling pathways in rice, which possesses two proteins (UVR8a and UVR8b) with high identities to AtUVR8, remain largely unknown. Here, UVR8a/b were found to be predominantly expressed in rice leaves and leaf sheaths, while the levels of UVR8b transcript and UVR8b protein were both higher than those of UVR8a. Compared to wild-type (WT) plants, uvr8b and uvr8a uvr8b rice mutants exposed to UV-B showed reduced UV-B-induced growth inhibition and upregulation of CHS and HY5 transcripts alongside UV-B acclimation. However, uvr8a mutant was similar to WT plants and exhibited changes comparable with WT. Overexpressing OsUVR8a/b enhanced UV-B-induced growth inhibition and acclimation to UV-B. UV-B was able to enhance the interaction between E3 ubiquitin ligase OsCOP1 and OsUVR8a/b, whereas the interaction of the homologous protein of Arabidopsis REPRESSOR OF UV-B PHOTOMORPHOGENESIS2 (AtRUP2) in rice with OsUVR8a/b was independent of UV-B. Additionally, OsUVR8a/b proteins were also found in the nucleus and cytoplasm even in the absence of UV-B. The abundance of OsUVR8 monomer showed an invisible change in the leaves of rice seedlings transferred from white light to that supplemented with UV-B, even though UV-B was able to weaken the interactions between OsUVR8a and OsUVR8b homo and heterodimers. Therefore, both OsUVR8a and OsUVR8b, which have different localization and response patterns compared with AtUVR8, function in the response of rice to UV-B radiation, whereas OsUVR8b plays a predominant role in this process.

Harnessing imaging tools to guide immunotherapy trials: summary from the National Cancer Institute Cancer Imaging Steering Committee workshop.

As the immuno-oncology field continues the rapid growth witnessed over the past decade, optimising patient outcomes requires an evolution in the current response-assessment guidelines for phase 2 and 3 immunotherapy clinical trials and clinical care. Additionally, investigational tools-including image analysis of standard-of-care scans (such as CT, magnetic resonance, and PET) with analytics, such as radiomics, functional magnetic resonance agents, and novel molecular-imaging PET agents-offer promising advancements for assessment of immunotherapy. To document current challenges and opportunities and identify next steps in immunotherapy diagnostic imaging, the National Cancer Institute Clinical Imaging Steering Committee convened a meeting with diverse representation among imaging experts and oncologists to generate a comprehensive review of the state of the field.

Safety and efficacy of nivolumab plus ipilimumab in patients with advanced renal cell carcinoma with brain metastases: CheckMate 920.

BACKGROUND: Nivolumab plus ipilimumab (NIVO + IPI) has demonstrated long-term efficacy and safety in patients with previously untreated, advanced renal cell carcinoma (aRCC). Although most phase 3 clinical trials exclude patients with brain metastases, the ongoing, multicohort phase 3b/4 CheckMate 920 trial (ClincalTrials.gov identifier NCT02982954) evaluated the safety and efficacy of NIVO + IPI in a cohort that included patients with aRCC and brain metastases, as reported here. METHODS: Patients with previously untreated aRCC and asymptomatic brain metastases received NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks × 4 followed by NIVO 480 mg every 4 weeks. The primary end point was the incidence of grade ≥3 immune-mediated adverse events (imAEs) within 100 days of the last dose of study drug. Key secondary end points were progression-free survival and the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1 (both determined by the investigator). Exploratory end points included overall survival, among others. RESULTS: After a minimum follow-up of 24.5 months (N = 28), no grade 5 imAEs occurred. The most common grade 3 and 4 imAEs were diarrhea/colitis (n = 2; 7%) and hypophysitis, rash, hepatitis, and diabetes mellitus (n = 1 each; 4%). The objective response rate was 32% (95% CI, 14.9%-53.5%) with a median duration of response of 24.0 months; 4 of 8 responders remained without reported progression. Seven patients (25%) had intracranial progression. The median progression-free survival was 9.0 months (95% CI, 2.9-12.0 months), and the median overall survival was not reached (95% CI, 14.1 months to not estimable). CONCLUSIONS: In patients who had previously untreated aRCC and brain metastases-a population with a high unmet medical need that often is underrepresented in clinical trials-the approved regimen of NIVO + IPI followed by NIVO showed encouraging antitumor activity and no new safety signals.

The rice germin-like protein OsGLP1 participates in acclimation to UV-B radiation.

Exposure to ultraviolet B radiation (UV-B) stress can have serious effects on the growth and development of plants. Germin-like proteins (GLPs) may be involved in different abiotic and biotic stress responses in different plants, but little is known about the role of GLPs in UV-B stress response and acclimation in plants. In the present study, knockout of GLP 8-14 (OsGLP1) using the CRISPR/Cas9 system resulted in mutant rice (Oryza sativa L.) plants (herein called glp1) that exhibited UV-B-dependent formation of lesion mimic in leaves. Moreover, glp1 grown under solar radiation (including UV-B) showed decreased plant height and increased leaf angle, but we observed no significant differences in phenotypes between wild-type (WT) plants and glp1 grown under artificial light lacking UV-B. Fv/Fm, Y (II) and the expression of many genes, based on RNA-seq analysis, related to photosynthesis were also only reduced in glp1, but not in WT, after transfer from a growth cabinet illuminated with artificial white light lacking UV-B to growth under natural sunlight. The genes-associated with flavonoid metabolism as well as UV resistance locus 8 (OsUVR8), phytochrome interacting factor-like 15-like (OsPIF3), pyridoxal 5'-phosphate synthase subunit PDX1.2 (OsPDX1.2), deoxyribodipyrimidine photolyase (OsPHR), and deoxyribodipyrimidine photolyase family protein-like (OsPHRL) exhibited lower expression levels, while higher expression levels of mitogen-activated protein kinase 5-like (OsMPK3), mitogen-activated protein kinase 13-like (OsMPK13), and transcription factor MYB4-like (OsMYB4) were observed in glp1 than in WT after transfer from a growth cabinet illuminated with artificial white light to growth under natural sunlight. Therefore, mutations in OsGLP1 resulted in rice plants more sensitive to UV-B and reduced expression of some genes for UV-B protection, suggesting that OsGLP1 is involved in acclimation to UV-B radiation.

eLearning and transurethral prostate surgery: virtual tools for a real training.

PURPOSE OF REVIEW: In the recent two decades, technological breakthrough has tremendously expanded the scope of transurethral prostate surgery. New gadgets and energy devices keep emerging to tackle benign prostatic obstruction, which was dealt with mainly by transurethral resection of prostate in the old days. Although this trend appears fascinating, it also means that urologists need quality training to attain surgical safety in performing these new surgeries. E-learning and simulation training may play an important role in modern urology training. RECENT FINDINGS: In this review, we would describe, using up-to-date evidence, the key components of simulation training, the types of simulators currently in use and their respective advantages and limitations. SUMMARY: Modern simulation technology enables surgical training in a realistic, reproducible and risk-free environment. Simulation training has been proven to improve both performers' confidence and objective scores in various transurethral prostate surgeries. Its use should therefore be advocated.

Five-year effectiveness of bariatric surgery on disease remission, weight loss, and changes of metabolic parameters in obese patients with type 2 diabetes: A population-based propensity score-matched cohort study.

AIMS: To compare disease remission rates, weight loss, and changes of metabolic parameters of patients after bariatric surgery with nonsurgical patients. METHODS: Based on the 2006-2017 Hospital Authority database, a population-based retrospective cohort of obese type 2 diabetes mellitus (T2DM) patients with and without bariatric surgery were identified. Surgical patients were matched with nonsurgical patients on 1-to-5 propensity score. Remission rates of diabetes, hypertension, and dyslipidaemia were reported annually up to 60 months. Changes in weight loss measurements (Body Mass Index [BMI], percentage of total weight loss [%TWL], percentage of excess weight loss [%EWL], and percentage of rebound in excess weight loss [%REWL]) and metabolic parameters (haemoglobin A1c [HbA1c ], systolic blood pressure [SBP], diastolic blood pressure [DBP], and low-density lipoprotein cholesterol [LDL-C]) were measured for both groups. RESULTS: Four hundred one surgical patients (310 restrictive surgeries; 91 bypass surgeries) and 1894 nonsurgical patients were included. Surgical patients had higher remission rates in diabetes and dyslipidaemia and better glycaemic control at 12 to 60 months (all Ps < .01). SBP and DBP were significantly lower for surgical group up to 12 months and similar between two groups after 12 months. Surgical patients had significantly lower BMI during follow-up period. %TWL and %EWL were higher in the surgery group (15.7% vs 3.7%; 48.8% vs 12.0%) at 60 months (P < .001); differences in %REWL between two groups were insignificant. The effectiveness of restrictive and bypass surgeries was similar at 60 months, although restrictive surgeries were slightly more effective in T2DM remission. CONCLUSIONS: Bariatric surgery was effective in weight loss, remission of diabetes, and dyslipidaemia in 5-year post-surgery.

Direct-to-Consumer Hospital Advertising and Domestic Medical Travel in the United States.

EXECUTIVE SUMMARY: Expanding hospitals' geographic market area has been proposed as a means to increase competition and reduce healthcare costs. However, most patients in the United States receive care locally and are unlikely to seek out distant hospitals, effectively limiting competition to local markets. We hypothesize that mass media advertising can help overcome patients' reluctance to travel for elective medical care. We examined hospitals' advertising in distant markets to determine whether their expenditures predict the number of patients who travel to those hospitals.We obtained data on 2015 advertising expenditures by 273 U.S. academic medical centers from a market research firm. Regression models examined associations between hospitals' advertising expenditures and patient volume metrics: inpatients, encounters, and charges originating from distant markets where the medical centers advertised. Results showed that hospitals' advertising expenditures in distant markets were associated with higher numbers of inpatient admissions, patient visits, and charges from those markets. Compared to the distant markets where they advertised, the hometown markets of these hospitals are smaller with lower per capita income, suggesting hospitals are seeking incremental patient volume from more lucrative markets.Findings suggest that advertising may familiarize patients with distant facilities, encouraging domestic medical travel and enabling broader geographic competition among hospitals.

The Radiolabeling of a Gly-Sar Dipeptide Derivative with Flourine-18 and Its Use as a Potential Peptide Transporter PET Imaging Agent.

: We have developed a novel fluorine-18 radiotracer, dipeptide 1, radiolabeled in two steps from mesylate 3. The initial radiolabeling is achieved in a short reaction time (10 min) and purified through solid-phase extraction (SPE) with modest radiochemical yields (rcy = 10 ± 2%, n = 5) in excellent radiochemical purity (rcp > 99%, n = 5). The de-protection of the tert-butyloxycarbonyl (Boc) and trityl group was achieved with mild heating under acidic conditions to provide 18F-tagged dipeptide 1. Preliminary analysis of 18F-dipeptide 1 was performed to confirm uptake by peptide transporters (PepTs) in human pancreatic carcinoma cell lines Panc1, BxPC3, and ASpc1, which are reported to express the peptide transporter 1 (PepT1) . Furthermore, we confirmed in vivo uptake of 18F-dipeptide tracer 1 using microPET/CT in mice harboring subcutaneous flank Panc1, BxPC3, and Aspc1 tumors. In conclusion, we have established the radiolabeling of dipeptide 1 with fluoride-18, and demonstrated its potential as an imaging agent which may have clinical applications for the diagnosis of pancreatic carcinomas.

Diagnostic Performance of 4D CT and Sestamibi SPECT/CT in Localizing Parathyroid Adenomas in Primary Hyperparathyroidism.

Background There currently is no consensus on the optimal localization procedure and imaging protocol for parathyroid adenoma. Parathyroid four-dimensional (4D) CT has emerged as a promising method for preoperative localization. Purpose To evaluate the diagnostic performance of parathyroid 4D CT and technetium 99m-sestamibi (hereafter, referred to as sestamibi) SPECT/CT in preoperative localization in patients with primary hyperparathyroidism. Materials and Methods This was a single-institution retrospective study of patients with primary hyperparathyroidism who underwent a combined imaging protocol of sestamibi SPECT/CT and 4D CT (noncontrast, contrast agent-enhanced, arterial, and delayed venous phases) acquired in a single setting from February 2013 to May 2016, with subsequent parathyroidectomy within 6 months. Reference standard for correct localization was on the basis of location denoted on operative reports, with pathologic confirmation of parathyroid adenoma or hyperplasia. By using a four-quadrant analysis, sensitivity, specificity, and area under the curve (AUC) for localization of the hyperfunctioning parathyroid gland or glands at sestamibi SPECT/CT and 4D CT were compared, per modality and in combination. Results Four hundred patients (319 women, 81 men; mean age, 61 years ± 14 [standard deviation]) were evaluated. Similar diagnostic performance was found in both combined 4D CT with sestamibi SPECT/CT and 4D CT alone (area under the curve [AUC], 0.88 [95% CI: 0.86, 0.90] and 0.87 [95% CI: 0.85, 0.90], respectively; P = .82). Both modalities outperformed sestamibi SPECT/CT (AUC, 0.78; 95% CI: 0.76, 0.81; P < .001). Four-dimensional CT showed higher sensitivity than did sestamibi SPECT/CT (sensitivity, 79.3% [414 of 522] vs 58.0% [303 of 522], respectively; P < .001). In a subset analysis, 4D CT had higher sensitivity than sestamibi SPECT/CT in patients with single-gland disease (sensitivity, 92.5% [297 of 321] vs 75.1% [241 of 321], respectively; P < .001) and with multigland disease (sensitivity, 58.2% [117 of 201] vs 30.8% [62 of 201], respectively; P < .001). Conclusion Four-dimensional CT provided superior preoperative localization compared with sestamibi SPECT/CT in patients with single and multigland disease. The combination of the two modalities did not improve diagnostic performance compared with four-dimensional CT alone. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sinha and Oates in this issue.

Effects of Oxytocin Administration on Cue-Induced Craving in Co-occurring Alcohol Use Disorder and PTSD: A Within-Participant Randomized Clinical Trial.

BACKGROUND: Individuals with alcohol use disorder (AUD) are much more likely to meet criteria for posttraumatic stress disorder (PTSD) than the general population. Compared to AUD alone, those with comorbid AUD-PTSD experience worse outcomes. Prior literature suggests that oxytocin, a hypothalamic neuropeptide, may be effective in the treatment of both AUD and PTSD when administered intranasally, although specific mechanisms remain elusive. METHODS: Forty-seven male patients with comorbid AUD-PTSD were administered intranasal oxytocin in a randomized, double-blind, dose-ranging (20 IU, 40 IU, and matched placebo), within-participant design with study visits at least 1 week apart. A cue-induced craving paradigm was conducted using each participant's preferred alcoholic beverage versus a neutral water cue. Self-reported alcohol craving and heart rate (HR) were recorded and analyzed using linear mixed-effect models. RESULTS: While alcohol cues significantly induced self-reported craving and increased HR compared to neutral water cues, neither dosage of oxytocin compared to placebo reduced self-reported cue-induced alcohol craving nor cue-induced changes in HR in patients with PTSD-AUD. CONCLUSIONS: These preliminary findings suggest that oxytocin does not affect cue-induced craving. Our results contribute to an ever-growing field of research investigating the effects of intranasal oxytocin on the symptoms of substance use disorders and will help further refine methodology and streamline future inquiries in this area.

Overexpression of OsIAAGLU reveals a role for IAA-glucose conjugation in modulating rice plant architecture.

KEY MESSAGE: OsIAAGLU could catalyze the reaction of IAA with glucose to generate IAA-glucose. Overexpression of OsIAAGLU in rice resulted in altered rice shoot architecture and root gravitropism. The distribution and levels of indole-3-acetic acid (IAA) within plant tissues are well known to play vital roles in plant growth and development. An important mechanism of regulating free IAA levels in monocots is formation of IAA ester conjugates. In this study, a cytosol-localized protein encoded by the rice gene of indole-3-acetic acid glucosyltransferase (OsIAAGLU) was found to catalyze the reaction of free IAA with glucose to generate IAA-glucose. Expression of OsIAAGLU could be induced by IAA and NAA. The number of tillers and leaf angle was significantly increased with a concomitant decrease in plant height and panicle length in the transgenic rice lines overexpressing OsIAAGLU compared to the wild-type (WT) plants. Phenotypes of iaaglu mutants constructed using the CRISPR/Cas9 system had no obvious differences with WT plants. Furthermore, overexpression of OsIAAGLU resulted in reduced sensitivity to IAA/NAA and altered gravitropic response of the roots in the transgenic plants. Free IAA contents in the leaves, root tips, and lamina joint of OsIAAGLU-overexpressing transgenic lines were lower than those of WT plants. These results support that OsIAAGLU could play a regulatory role in IAA homeostasis and rice architecture.

Predictors of Response and Survival in Locally Advanced Adenocarcinoma of the Pancreas Following Neoadjuvant GTX with or Without Radiation Therapy.

LESSONS LEARNED: There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer.Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement. BACKGROUND: In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (≥2 mm margins), and survival. METHODS: All patients had baseline magnetic resonance imaging (MRI) and/or computed tomography (CT) scans and endoscopic ultrasound. A baseline positron emission tomography-computed tomography (PET-CT) was performed in 39 patients. The scans were reviewed by two radiologists.GTX (gemcitabine 750 mg/m2 and docetaxel 30 mg/m2 on days 4 and 11 with capecitabine 1,500 mg/m2 days 1-14) was administered on a 3-week schedule for 6 cycles to patients with both arterial and venous-only involvement. Patients in the arterial arm received GX/RT before surgery, and those in the venous arm received GX/RT after R1 resection. Standard-dose RT was delivered by intensity-modulated radiation therapy (IMRT) or conformal fields to 5040 cGy along with capecitabine for 5 days and gemcitabine on day 5 of weeks 1, 2, 4, and 5 of RT, starting with the first full week of RT.A cancer antigen test 19-9 (CA 19-9) was obtained at baseline and days 4 and 11 of each cycle. The rate of change in CA 19-9 was calculated using the formula: (Log10 CA 19-9 time 0) - (Log10 CA 19-9 at 9 weeks)/9 weeks. This was derived based on the observation that the fall in CA 19-9 following effective chemotherapy is a second-order function. RESULTS: Of the 34 patients with arterial involvement and 11 with extensive venous involvement who met the eligibility criteria and began GTX, only 5 patients in the arterial arm did not undergo subsequent resection. The remaining 40 patients were included in this analysis of presenting parameters with respect to R0 resection, disease-free survival (DFS), and overall survival (OS). R0 resection was achieved in 28 of 40 patients (70%), and R1 resection in the remaining 12 (30%). The OS after R0 resection was a median 37 months (95% confidence interval [CI]: 29.3-44.7) compared with 29 months (95% CI: 28.5-41.5) for those with R1 resection.Excluding four postoperative deaths, median DFS for the 25 (71%) with R0 resection was 31 months (95% CI: 11.3-51.1), and the median DFS for R1 resection was only 14 months (95% CI: 11.1-17). Eleven of the twenty-eight (39%) patients achieving R0 resection have not relapsed (median = 45 months, range = 25-71 months). CONCLUSION: R0 resection, the goal of neoadjuvant treatment, can be achieved in 70% of patients presenting with locally advanced pancreatic cancer. The median DFS was 31 months (95% CI: 11. 3-51.1). No relationship was found with tumor size, degree of vascular involvement, carcinoembryonic antigen test (CEA), CA 19-9, degree of tumor regression on scan, fall in CA 19-9, or SUV on PET scan and subsequent survival.

Phytotoxicity testing of diesel-contaminated water using Petunia grandiflora Juss. Mix F1 and Marigold-Nemo Mix (Tagetes patula L.).

Tagetes patula (marigold) and Petunia grandiflora (petunia) have been shown to exhibit potential in phytoremediation of environmental pollutants including heavy metals and textile dyes. To investigate their phytoremediation potential of diesel, it was necessary to evaluate diesel phytotoxicity of these two ornamental plants. Marigold and petunia seeds were incubated, for 10 and 15 days, respectively, in deionised water contaminated with 0 to 4%, v/v, diesel in Petri dishes in a growth room with continuous lighting at 25 °C. It was found that as far as seed germination was concerned, petunia was less sensitive than marigold to 4% diesel in water. In contrast, petunia exhibited poorer seedling root growth than marigold in the presence of diesel contamination. This finding of differential sensitivity of these two ornamental plants to diesel-contaminated water during germination and seedling growth has not been reported before. Therefore, the implications of phytotoxicity evaluation and comparison between different species or genotypes of plants at both seed germination and postgermination seedling growth should both be taken into consideration in screening tolerant plants for phytoremediation.

Targeted Metabolomics Approach To Detect the Misuse of Steroidal Aromatase Inhibitors in Equine Sports by Biomarker Profiling.

The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast elimination times render the direct detection approach ineffective as the detection window is short. A targeted metabolomics approach is a plausible alternative to the conventional direct detection approach for controlling the misuse of AAS in sports. Because the administration of AAS of the same class may trigger similar physiological responses or effects in the body, it may be possible to detect such administrations by monitoring changes in the endogenous steroidal expression profile. This study attempts to evaluate the viability of using the targeted metabolomics approach to detect the administration of steroidal aromatase inhibitors, namely androst-4-ene-3,6,17-trione (6-OXO) and androsta-1,4,6-triene-3,17-dione (ATD), in horses. Total (free and conjugated) urinary concentrations of 31 endogenous steroids were determined by gas chromatography-tandem mass spectrometry for a group of 2 resting and 2 in-training thoroughbred geldings treated with either 6-OXO or ATD. Similar data were also obtained from a control (untreated) group of in-training thoroughbred geldings (n = 28). Statistical processing and chemometric procedures using principle component analysis and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) have highlighted 7 potential biomarkers that could be used to differentiate urine samples obtained from the control and the treated groups. On the basis of this targeted metabolomic approach, the administration of 6-OXO and ATD could be detected for much longer relative to that of the conventional direct detection approach.