Pelvic MRI after induction chemotherapy and before long-course chemoradiation therapy for rectal cancer: What are the imaging findings?

OBJECTIVES: To determine the appearance of rectal cancer on MRI after oxaliplatin-based chemotherapy (ICT) and make a preliminary assessment of MRI's value in predicting response to total neoadjuvant treatment (TNT). METHODS: In this IRB-approved, HIPAA-compliant, retrospective study between 1 January 2010-20 October 2014, pre- and post-ICT tumour T2 volume, relative T2 signal intensity (rT2SI), node size, signal intensity and border characteristics were assessed in 63 patients (65 tumours) by three readers. The strength of association between the reference standard of histopathological percent tumour response and tumour volume change, rT2SI and lymph node characteristics was assessed with Spearman's correlation coefficient and Wilcoxon's rank sum test. Cox regression was used to assess association between DFS and radiological measures. RESULTS: Change in T2 volume was not associated with TNT response. Change in rT2SI showed correlation with TNT response for one reader only using selective regions of interest (ROIs) and borderline correlation with response using total volume ROI. There was a significant negative correlation between baseline and post-ICT node size and TNT response (r = -0.25, p = 0.05; r = -0.35, p = 0.005, readers 1 and 2, respectively). Both baseline and post-induction median node sizes were significantly smaller in complete responders (p = 0.03, 0.001; readers 1 and 2, respectively). Change in largest baseline node size and decrease in post-ICT node signal heterogeneity were associated with 100% tumour response (p = 0.04). Nodal sizes at baseline and post-ICT MRI correlated with DFS. CONCLUSION: In patients undergoing post-ICT MRI, tumour volume did not correlate with TNT response, but decreased lymph node sizes were significantly associated with complete response to TNT as well as DFS. Relative T2SI showed borderline correlation with TNT response. KEY POINTS: • MRI-based tumour volume after induction chemotherapy and before chemoradiotherapy did not correlate with overall tumour response at the end of all treatment. • Lymph node size after induction chemotherapy and before chemoradiotherapy was strongly associated with complete pathological response after all treatment. • Lymph node sizes at baseline and post-induction chemotherapy MRI correlated with disease-free survival.

Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.

Approximately 200 BRAF mutant alleles have been identified in human tumours. Activating BRAF mutants cause feedback inhibition of GTP-bound RAS, are RAS-independent and signal either as active monomers (class 1) or constitutively active dimers (class 2). Here we characterize a third class of BRAF mutants-those that have impaired kinase activity or are kinase-dead. These mutants are sensitive to ERK-mediated feedback and their activation of signalling is RAS-dependent. The mutants bind more tightly than wild-type BRAF to RAS-GTP, and their binding to and activation of wild-type CRAF is enhanced, leading to increased ERK signalling. The model suggests that dysregulation of signalling by these mutants in tumours requires coexistent mechanisms for maintaining RAS activation despite ERK-dependent feedback. Consistent with this hypothesis, melanomas with these class 3 BRAF mutations also harbour RAS mutations or NF1 deletions. By contrast, in lung and colorectal cancers with class 3 BRAF mutants, RAS is typically activated by receptor tyrosine kinase signalling. These tumours are sensitive to the inhibition of RAS activation by inhibitors of receptor tyrosine kinases. We have thus defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.

Innovations to support hydration care across health and social care.

It is known that the primary cause of dehydration in elderly care is caused by a person not regularly drinking enough. Dehydration is a much-publicised national concern, associated with poor outcomes of care and acute hospital admissions. However, in November last year, NHS England stated that the scale of dehydration is not known; in comparison, it confirmed at least three million people are at risk of malnutrition. The stark comparison in information occurs because there is no nationally recognised screening tool to identify who is at risk of dehydration. An innovative nursing role, focused on finding solutions to reduce the risk of dehydration in the care of older and vulnerable persons, has led to the development of a simple dehydration screening tool called 'ROC to drink' (ROC stands for 'reliance on a carer'), which focuses on the level of support needed to drink. An innovative tea cup has been designed to help raise standards for monitoring drinks and raise awareness about intake.

MRI for evaluation of treatment response in rectal cancer.

MRI plays an increasingly pivotal role in the clinical staging of rectal cancer in the baseline and post-treatment settings. An accurate evaluation of response to neoadjuvant treatment is crucial because of its major influence on patient management and quality of life. However, evaluation of treatment response is challenging for both imaging and clinical assessments owing to treatment-related inflammation and fibrosis. At one end of the spectrum are clinical yT4 rectal cancers, wherein precise post-treatment MRI evaluation of tumour spread is particularly important for avoiding unnecessary exenterative surgery. At the other extreme, for tumours with clinical near-complete response or clinical complete response to neoadjuvant treatment, less invasive treatment may be suitable instead of the standard surgical approach such as, for example, a "Watch and Wait" approach or perhaps local excision. Ideally, the goal of post-treatment MRI evaluation would be to identify these subgroups of patients so that they might be spared unnecessary surgical intervention. It is known that post-chemoradiation therapy restaging using conventional MR sequences is less accurate than baseline staging, particularly in confirming T0 disease, largely owing to the difficulty in distinguishing fibrosis, oedema and normal mucosa from small foci of residual tumour. However, there is a growing utilization of multiparametric MRI, which has superseded other types of evaluations and requires review and periodic re-evaluation. This commentary discusses the current status of multiparametric MRI in the post-treatment setting and the challenges facing imaging in general in the accurate determination of treatment response.

Zoomed echo-planar diffusion tensor imaging for MR tractography of the prostate gland neurovascular bundle without an endorectal coil: a feasibility study.

PURPOSE: The purpose of this study was to assess the feasibility of zoomed echo-planar imaging (EPI) diffusion tensor imaging (DTI) with 2-channel parallel transmission (pTx) for MR tractography of the periprostatic neurovascular bundle (NVB) without an endorectal coil, and to compare its performance to that of conventionally acquired DTI. METHODS: 8 healthy males (28.9 ± 4.6 years) underwent pelvic phased-array coil prostate MRI on a 3T system using both zoomed-EPI DTI (z-DTI) with 2-channel pTx and conventional single-shot spin-echo EPI DTI (c-DTI) acquisitions with 6 encoding directions and b-values of 0 and 1000 s/mm(2). Fractional anisotropy (FA) maps and tractography analysis incorporating 3D visualization of the NVB were performed from each acquisition. Fiber tract counts, estimated signal-to-noise ratio (eSNR), and image quality measures of the FA maps and NVB tractography were compared. Quantitative and image quality measures were compared using Wilcoxon signed rank tests. RESULTS: 3 of 8 subjects had no tracts detected with c-DTI acquisition, while all 8 had tracts detected with z-DTI. z-DTI acquisition yielded significantly more fiber tracts (c-DTI: 77 ± 116 tracts; z-DTI: 430 ± 228 tracts; p = 0.019) and higher eSNR (c-DTI: 2.9 ± 1.2; z-DTI: 13.17 ± 9.9; p = 0.014). Relative to c-DTI acquisitions, z-DTI FA maps showed significantly reduced artifact (p = 0.008) and reduced anatomic distortion of the prostate (p = 0.010), while z-DTI tractography showed significantly better overall visual quality (p = 0.011), tract symmetry (p = 0.010), tract coherence (p = 0.011), and subjective similarity to the actual NVB (p = 0.011). CONCLUSION: Zoomed-EPI DTI acquisition for tractography of the prostate gland NVB improves quantitative and qualitative measures of image and tract fiber quality, allowing tractography of the NVB at 3T without using an endorectal coil.

A Multidisciplinary Approach to Improving Appropriate Follow-Up Imaging of Ovarian Cysts: A Quality Improvement Initiative.

PURPOSE: Incidental ovarian cysts are frequently detected on imaging. Despite published follow-up consensus statements, there remains variability in radiologist follow-up recommendations and clinician practice patterns. The aim of this study was to evaluate if collaborative ovarian cyst management recommendations and a radiologist decision support tool can improve adherence to follow-up recommendations. METHODS: Gynecologic oncologists and abdominal radiologists convened to develop collaborative institutional recommendations for the management of incidental, asymptomatic simple ovarian cysts detected on ultrasound, CT, and MRI. The recommendations were developed by modifying the published consensus recommendations developed by the Society of Radiologists in Ultrasound on the basis of local practice patterns and the experience of the group members. A less formal process involved the circulation of the published consensus recommendations, followed by suggestions for revisions and subsequent consensus, in similar fashion to the ACR Incidental Findings Committee II. The recommendations were developed by building on the published work of experienced groups to provide the authors' medical community with a set of recommendations that could be endorsed by both the Department of Gynecology and the Department of Radiology to provide supportive guidance to the clinicians who manage incidental ovarian cysts. The recommendations were integrated into a radiologist decision support tool accessible from the dictation software. Nine months after tool launch, institutional review board approval was obtained, and radiology reports mentioning ovarian cysts in the prior 34 months were retrospectively reviewed. For cysts detected on ultrasound, adherence rates to Society of Radiologists in Ultrasound recommendations were calculated for examinations before tool launch and compared with adherence rates to the collaborative institutional recommendations after tool launch. Additionally, electronic medical records were reviewed to determine the follow-up chosen by the clinician. RESULTS: For cysts detected on ultrasound, radiologist adherence to recommendations improved from 50% (98 of 197) to 80% (111 of 139) (P < .05). Overmanagement decreased from 34% (67 of 197) to 10% (14 of 139) (P < .05). A recommendation was considered "overmanaged" if the radiologist recommended follow-up when it was not indicated or if the recommended follow-up time was at a shorter interval than indicated. Clinician adherence to radiologist recommendations showed statistically nonsignificant improvement from 49% (36 of 73) to 57% (27 of 47) (P = .5034). CONCLUSIONS: Management recommendations developed through collaboration with clinicians may help standardize follow-up of ovarian cysts and reduce overutilization.

Simultaneous Multislice Accelerated Free-Breathing Diffusion-Weighted Imaging of the Liver at 3T.

PURPOSE: To perform image quality comparison between accelerated multiband diffusion acquisition (mb2-DWI) and conventional diffusion acquisition (c-DWI) in patients undergoing clinically indicated liver MRI. METHODS: In this prospective study 22 consecutive patients undergoing clinically indicated liver MRI on a 3-T scanner equipped to perform multiband diffusion-weighed imaging (mb-DWI) were included. DWI was performed with single-shot spin-echo echo-planar technique with fat-suppression in free breathing with matching parameters when possible using c-DWI, mb-DWI, and multiband DWI with a twofold acceleration (mb2-DWI). These diffusion sequences were compared with respect to various parameters of image quality, lesion detectability, and liver ADC measurements. RESULTS: Accelerated mb2-DWI was 40.9% faster than c-DWI (88 vs. 149 s). Various image quality parameter scores were similar or higher on mb2-DWI when compared to c-DWI. The overall image quality score (averaged over the three readers) was significantly higher for mb-2 compared to c-DWI for b = 0 s/mm(2) (3.48 ± 0.52 vs. 3.21 ± 0.54; p = 0.001) and for b = 800 s/mm(2) (3.24 ± 0.76 vs. 3.06 ± 0.86; p = 0.010). Total of 25 hepatic lesions were visible on mb2-DWI and c-DWI, with identical lesion detectability. There was no significant difference in liver ADC between mb2-DWI and c-DWI (p = 0.12). Bland-Altman plot demonstrates lower mean liver ADC with mb2-DWI compared to c-DWI (by 0.043 × 10(-3) mm(2)/s or 3.7% of the average ADC). CONCLUSION: Multiband technique can be used to increase acquisition speed nearly twofold for free-breathing DWI of the liver with similar or improved overall image quality and similar lesion detectability compared to conventional DWI.

PET/MRI for the evaluation of patients with lymphoma: initial observations.

OBJECTIVE: The objective of our study was to assess the role of recently introduced hybrid PET/MRI in the evaluation of lymphoma patients using PET/CT as a reference standard. SUBJECTS AND METHODS: In this prospective study 28 consecutive lymphoma patients (18 men, 10 women; mean age, 53.6 years) undergoing clinically indicated PET/ CT were subsequently imaged with PET/MRI using residual FDG activity from the PET/ CT study. Blinded readers evaluated PET/CT (reference standard), PET/MRI, and diffusion-weighted imaging (DWI) studies separately; for each study, they assessed nodal and extranodal involvement. Each FDG-avid nodal station was marked and compared on DWI, PET/MRI, and PET/CT. Modified Ann Arbor staging was performed and compared between PET/MRI and PET/CT. The maximum standardized uptake value (SUVmax) on PET/MRI for FDG-avid nodal lesions was compared with the SUVmax on PET/CT. The apparent diffusion coefficient (ADC) for FDG-avid nodal lesions was compared to SUVmax on PET/MRI. RESULTS: Fifty-one FDG-avid nodal groups were identified on PET/CT in 13 patients. PET/MRI identified 51 of these nodal groups with a sensitivity of 100%. DWI identified 32 nodal groups for a sensitivity of 62.7%. PET/MRI staging and PET/CT staging were concordant in 96.4% of patients. For the one patient with discordant staging results, disease was correctly upstaged to stage IV on the basis of the PET/MRI finding of bone marrow involvement, which was missed on PET/CT. DWI staging was concordant with PET/CT staging in 64.3% of the patients. The increased staging accuracy of PET/MRI relative to DWI was significant (p=0.004). SUVmax measured on PET/MRI and PET/CT showed excellent statistically significant correlation (r=0.98, p<0.001). There was a poor negative correlation between ADC and SUVmax (r=-0.036, p=0.847). CONCLUSION: PET/MRI can be used to assess disease burden in lymphoma with sensitivity similar to PET/CT and can be a viable alternative for lymphoma staging and follow-up.

Transition zone prostate cancer: revisiting the role of multiparametric MRI at 3 T.

OBJECTIVE. The purpose of this study was to retrospectively evaluate the impact of multiparametric prostate MRI, including diffusion-weighted imaging (DWI) performed using different b values as well as dynamic contrast-enhanced MRI (DCE-MRI) on the accuracy, sensitivity, and specificity for transition zone (TZ) tumor detection and localization. MATERIALS AND METHODS. We included 106 prostate cancer patients (mean age [± SD], 62 ± 7 years) who underwent 3-T MRI with a pelvic phased-array coil before radical prostatectomy. Three radiologists independently reviewed cases to record the likelihood of tumor in each of six TZ regions. Scores were initially assigned using T2-weighted imaging alone, reassigned after integration of DWI at b = 1000 s/mm(2) and corresponding apparent diffusion coefficient (ADC) maps, reassigned again after integration of DWI at b = 2000 s/mm(2), and reassigned a final time after integration of DCE-MRI. Generalized estimating equations based on binary logistic regression were used to compare sessions for TZ tumor detection, using prostatectomy findings as reference standard. RESULTS. Of the TZ sextants, 9.7% (62/636) contained tumor. All readers had higher sensitivity for T2-weighted imaging integrated with DWI at b = 1000 s/mm(2) and ADC compared with T2-weighted imaging alone (reader 1, 54.8% vs 33.9%; reader 2, 53.2% vs 22.6%; and reader 3, 50.0% vs 19.4% [p ≤ 0.002]); two readers had further increased sensitivity also incorporating b = 2000 s/mm(2) (reader 1, 74.2% and reader 2, 62.9%; p ≤ 0.011), and one reader had further increased sensitivity also incorporating both b = 2000 s/mm(2) and DCE-MRI (reader 3, 61.3%, p = 0.013). DCE-MRI otherwise did not improve sensitivity (p ≥ 0.054). Other measures were similar across the four sessions (reader 1, specificity 97.4-98.3% and accuracy 91.2-95.9%; reader 2, specificity 95.8-98.4% and accuracy 91.0-92.6%; reader 3, specificity 90.9-96.7% and accuracy 88.1-89.2%). CONCLUSION. DWI assists TZ tumor detection through higher sensitivity, particularly when using a very high b value; DCE-MRI lacks further additional benefit.

New OPTN/UNOS classification system for nodules in cirrhotic livers detected with MR imaging: effect on hepatocellular carcinoma detection and transplantation allocation.

PURPOSE: To assess the effect of the new Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) policy on hepatocellular carcinoma (HCC) detection and liver transplant allocation in patients with cirrhosis undergoing dynamic contrast material-enhanced liver magnetic resonance (MR) imaging. MATERIALS AND METHODS: In this HIPAA-compliant institutional review board-approved retrospective study with waiver of informed consent, 247 patients (196 men, 51 women; mean age, 60 years ± 11 [standard deviation]) with liver cirrhosis who underwent evaluation for HCC with MR imaging were identified via database search. Three radiologists independently reviewed images and identified number and size of HCC based on criteria within either the prior or revised policy. Based on these interpretations, priority for liver transplantation for each patient was determined with prior and revised transplantation allocation criteria. HCC detection was compared between sessions by using McNemar tests, and interreader agreement for detection of at least one HCC was assessed by using κ coefficients. RESULTS: All three readers detected significantly more 1-2-cm HCCs with the revised policy (readers detected 22, eight, and 20 1-2-cm HCCs) versus the prior policy (no reader detected 1-2-cm HCCs) (P ≤ .031). All readers detected significantly fewer 2-5-cm HCCs with the revised policy (readers detected eight, 13, and 14 2-5-cm HCCs) versus the prior policy (readers detected 24, 21, and 24 2-5-cm HCCs) (P ≤ .027). For all readers, fewer patients met criteria for increased transplantation priority with the revised versus the prior policy (number of patients who received increased priority for the three readers were 4.9% [12 of 247] vs 9.3% [23 of 247]; 5.7% [14 of 247] vs 8.1% [20 of 247]; and 6.9% [17 of 247] vs 8.9% [22 of 247]). Interreader agreement was substantial for the prior policy (κ = 0.607) and almost perfect for the revised policy (κ = 0.813). CONCLUSION: Among cirrhotic patients who underwent evaluation for HCC with MR imaging, the revised OPTN/UNOS policy led to increased detection of 1-2-cm HCCs, decreased detection of 2-5-cm HCCs, and fewer patients who met criteria for increased transplant priority.

Imaging patterns of intraductal papillary mucinous neoplasms of the pancreas: an illustrated discussion of the International Consensus Guidelines for the Management of IPMN.

Intraductal papillary mucinous neoplasms (IPMN) are being diagnosed with increasing frequency, necessitating an algorithm to help stratify patients into low- and high-risk groups, for follow-up versus more invasive evaluation. New evidence concerning their natural history and overall risk of malignancy has emerged since the 2006 International Association of Pancreatology consensus guidelines, prompting an update in 2012, that distinguishes radiologic 'worrisome features' from 'high-risk stigmata'. The aim of this article is to illustrate, with case examples, the variable imaging patterns of IPMN and how their radiologic features, such as cyst size and mural nodules, are interpreted in the context of the new 2012 guidelines. The 2012 and 2006 guidelines will be compared and discussed with reference to additional studies that have since been published. Despite these guidelines, lingering uncertainty remains about the natural history of IPMN, a source of unease to both radiologists and referring clinicians alike, mandating further refinement of clinical and radiologic parameters predictive of malignancy. Emerging data regarding the risk of extrapancreatic malignancy, as well as synchronous or metachronous pancreatic ductal adenocarcinoma remote in location from a branch duct IPMN are also reviewed. With the expanding research and evolving understanding of this clinicopathologic entity across the globe, radiologists will continue to play an important role in the management of patients with IPMN.

Differentiation of Malignant Omental Caking from Benign Omental Thickening using MRI.

PURPOSE: To determine multi-parametric MRI features that can help differentiate malignant omental caking from benign omental thickening in the setting of portal hypertension. METHODS: We identified 19 patients with an abnormal omentum on MRI and an available reference standard: 11 patients with portal hypertension and benign omental thickening (9 male, 2 female, mean age 58 ± 6 years) and 8 patients with metastatic omental caking (4 male, 4 female, mean age 61 ± 13 years). Criteria for benign omental thickening were no evidence of malignancy for at least 24 months of follow-up (n = 7), negative ascites cytology (n = 2), or absence of malignancy on pathologic analysis of liver explant (n = 2). Criteria for omental malignancy were positive omental biopsy (n = 6) or ascites cytology (n = 2). Two radiologists (R1 and R2) evaluated characteristics of the thickened omentum on MRI. RESULTS: Findings occurring with significantly higher frequency in malignant omental caking were hyperintensity on high b-value diffusion-weighted imaging (DWI) (R1 88% vs. 0%, R2 88% vs. 0%), hyperenhancement (R1 75% vs. 0%, R2 75% vs. 0%), and convex outer omental contour (R1 88% vs. 0%, R2 75% vs. 9%) (all p ≤ 0.001); discrete omental nodules were significantly more frequent in malignant omental thickening for R1 (63% vs. 0%, p = 0.005). Features not significantly different between groups included decreased ADC, T2 hyperintensity, vessels coursing through the omentum, moderate/large volume ascites, splenomegaly, and mesenteric edema (all p ≥ 0.058). CONCLUSION: Abnormal signal on DWI, hyperenhancement, and convex outer contour are helpful MRI features to differentiate malignant from benign omental thickening.

Determinants of HIV-1 drug resistance in treatment-naïve patients and its clinical implications in an antiretroviral treatment program in Cameroon.

INTRODUCTION: Facing the rapid scale-up of antiretroviral treatment (ART) programs in resource-limited settings, monitoring of treatment outcome is essential in order to timely detect and tackle drawbacks [1]. METHODS: In a prospective cohort study, 300 consecutive patients starting first-line ART were enrolled between 2009 and2010 in a large HIV treatment centre in rural Cameroon. Patients were followed up for 12 months. Virologic failure was defined as a VL >1000 cop/mL at month 12. Besides CD4 and viral load (VL) analysis, HIV-1 drug resistance testing was performed in patients with VL>1000 copies (c)/mL plasma. In those patients and controls, minority HIV-1 drug resistance mutations at baseline, and plasma drug levels were analyzed in order to identify the risk factors for virologic failure. RESULTS: Most enrolled patients (71%) were female. At baseline median CD4 cell count was 162/µL (IQR 59-259), median log10 VL was 5.4 (IQR 5.0-5.8) c/mL, and one-third of patients had World Health Organisation (WHO) stage 3 or 4; 30 patients died during follow-up. Among all patients who completed follow-up 38/238 had virologic failure. These patients were younger, had lower CD4 cell counts and more often had WHO stage 3 or 4 at baseline compared to patients with VL<1000c/mL. Sixty-three percent of failing patients (24/38) had at least one mutation associated with high-level drug resistance. The M184V mutation was the most frequently detected nucleoside reverse transcriptase inhibitor (NRTI) mutation (n=18) followed by TAMs (n=5) and multi-NRTI resistance mutations (n=4). The most commonly observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance mutations were K103N (n=10), Y181C (n=7), and G190A (n=6). Drug resistance mutations at baseline were detected in 12/65 (18%) patients, in 6 patients with and 6 patients without virological failure (p=0.77). Subtherapeutic NNRTI levels (OR 6.67, 95% CI 1.98-22.43, p<0.002) and poorer adherence (OR 1.54, 95% CI 1.00-2.39, p=0.05) were each associated with higher risk of virologic failure in the matched pair analysis. Unavailability of ART at the treatment centre was the single most common cause (37%) for incomplete adherence in these patients. CONCLUSIONS: Virologic failure after one year of first-line ART in rural Cameroon was not associated with transmitted drug resistance, but with reduced drug plasma levels and incomplete adherence. Strategies to assure adherence and uninterrupted drug supply are important factors for therapy success.

MRI phenotype in renal cancer: is it clinically relevant?

Renal cell carcinoma (RCC) is most commonly diagnosed as an incidental finding on cross-sectional imaging and represents a significant clinical challenge. Although most patients have a surgically curable lesion at the time of diagnosis, the variability in the biologic behavior of the different histologic subtypes and tumor grade of RCC, together with the increasing array of management options, creates uncertainty for the optimal clinical approach to individual patients. State-of-the-art magnetic resonance imaging (MRI) provides a comprehensive assessment of renal lesions that includes multiple forms of tissue contrast as well as functional parameters, which in turn provides information that helps to address this dilemma. In this article, we review this evolving and increasingly comprehensive role of MRI in the detection, characterization, perioperative evaluation, and assessment of the treatment response of renal neoplasms. We emphasize the ability of the imaging "phenotype" of renal masses on MRI to help predict the histologic subtype, grade, and clinical behavior of RCC.

Quantification of Thiopurine/UVA-Induced Singlet Oxygen Production.

Thiopurines were examined for their ability to produce singlet oxygen ((1)O(2)) with UVA light. The target compounds were three thiopurine prodrugs, azathioprine (Aza), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), and their S-methylated derivatives of 6-methylmercaptopurine (me6-MP) and 6-methylthioguanine (me6-TG). Our results showed that these thiopurines were efficient (1)O(2) sensitizers under UVA irradiation but rapidly lost their photoactivities for (1)O(2) production over time by a self-sensitized photooxidation of sulfur atoms in the presence of oxygen and UVA light. The initial quantum yields of (1)O(2) production were determined to be in the range of 0.30-0.6 in aqueous solutions. Substitution of a hydrogen atom with a nitroimidazole or methyl group at S decreased the efficacy of photosensitized (1)O(2) production as found for Aza, me6-MP and me6-TG. (1)O(2)-induced formation of 8-oxo-7,8-dihydro-2'-dexyguanosine (8-oxodGuo) was assessed by incubation of 6-methylthiopurine/UVA-treated calf thymus DNA with human repair enzyme 8-oxodGuo DNA glycosylase (hOGG1), followed by apurinic (AP) site determination. Because more 8-oxodGuo was formed in Tris D(2)O than in Tris H(2)O, (1)O(2) is implicated as a key species in the reaction. These findings provided quantitative information on the photosensitization efficacy of thiopurines and to some extent revealed the correlations between photoactivity and phototoxicity.

Dehydration: why is it still a problem?

Reports from organisations such as the Care Quality Commission have identified many hospital patients, particularly older people, are suffering from dehydration. A range of national initiatives have emphasised the importance of hydration and nutrition, and offered guidance to help address shortcomings, yet the problems persist. This article examines the interplay of factors that affect the assessment and identification of dehydration, and its prevention. It also offers strategies to help nurses to ensure patients receive adequate hydration.