Mitochondrial quinone redox states as a marker of mitochondrial metabolism.

Mitochondrial and thus cellular energetics are highly regulated both thermodynamically and kinetically. Cellular energetics is of prime importance in the regulation of cellular functions since it provides ATP for their accomplishment. However, cellular energetics is not only about ATP production but also about the ability to re-oxidize reduced coenzymes at a proper rate, such that the cellular redox potential remains at a level compatible with enzymatic reactions. However, this parameter is not only difficult to assess due to its dual compartmentation (mitochondrial and cytosolic) but also because it is well known that most NADH in the cells is bound to the enzymes. In this paper, we investigated the potential relevance of mitochondrial quinones redox state as a marker of mitochondrial metabolism and more particularly mitochondrial redox state. We were able to show that Q2 is an appropriate redox mediator to assess the mitochondrial quinone redox states. On isolated mitochondria, the mitochondrial quinone redox states depend on the mitochondrial substrate and the mitochondrial energetic state (phosphorylating or not phosphorylating). Last but not least, we show that the quinones redox state response allows to better understand the Krebs cycle functioning and respiratory substrates oxidation. Taken together, our results suggest that the quinones redox state is an excellent marker of mitochondrial metabolism.

What women want: A mixed-methods study of women's health priorities, preferences, and experiences in care in three Rwandan rural districts.

OBJECTIVE: To explore Rwandan women's experiences, priorities, and preferences in accessing health care for non-pregnancy-related conditions and inform development of healthcare services related to these conditions among women of reproductive age at district hospitals and health centers in Rwanda. METHODS: We used a mixed-methods, exploratory sequential design. Semi-structured qualitative interviews were conducted with Rwandan women and coded thematically. A cross-sectional quantitative survey based on the qualitative data was administered to women attending health centers. RESULTS: Seventeen interviews and 150 surveys were conducted. Women identified conditions including back pain, gynecologic cancers, and abnormal vaginal bleeding as concerns. They generally reported positive experiences while accessing health care and knowledge of accessing health care. Barriers to care were identified, including transportation costs and inability to miss work. Women expressed a desire for more control over their care and the importance of maintaining their dignity while accessing health care. CONCLUSION: These findings provide useful insights to inform development of non-pregnancy-related healthcare services for women in Rwanda according to their priorities and preferences. The reported end-user health concerns, barriers to care, and diminished control over their care point to a need to evolve health systems around user-tailored needs and design interventions optimizing access whilst promoting dignified care.

[Outpatient laparoscopic hysterectomy in France: A monocentric randomized trial]. / Hystérectomie cœlioscopique ambulatoire en France : étude randomisée unicentrique.

OBJECTIVE: To demonstrate the feasibility of outpatient laparoscopic hysterectomy using the assessment of post-operative quality of life. METHODS: A prospective randomized single-center trial was performed in France between 2013 and 2016. A total of 42 patients needed laparoscopic hysterectomy was included. Postoperative quality of life was assessed using the standardized Euroquol questionnaire. Patients filled the score before the operation and then on the 3rd and 30th postoperative day. Secondary outcomes were assessment of postoperative pain, overall quality of life, analgesic use, and anxiety. The patients were randomized into two groups, group A with a conventional hospital stay of 2 to 3 days and group B with a short stay and a discharge the day after the intervention. RESULTS: Twenty-one patients were randomized to group A as well as group B. We did not find any significant differences between the two groups in our study either on our primary outcome or in the seconds ones. On day 3, the average of Euroquol score was 0.68 for group A against 0.50 for group B (P=0.05). Likewise, the scores for postoperative pain were similar with 70.6 in group A and 61.8 in group B (P=0.21). The trend was the same for quality of life score or anxiety. CONCLUSION: Our study shows the possibility and the safety of outpatient laparoscopic hysterectomy.

Culturally sensitive palliative care in humanitarian action: Lessons from a critical interpretive synthesis of culture in palliative care literature.

OBJECTIVE: There is growing recognition of the importance of increasing preparedness for and the provision of palliative care in humanitarian crises. The primary objective of this review is to interpret the existing literature on culture and palliative care to query the recommendation that humanitarian healthcare providers, teams, and organizations integrate palliative care into their practice in ways that are attentive to and respectful of cultural differences. METHODS: A critical interpretive synthesis was applied to a systematic literature review guided by the PRISMA framework. Analysis was based on directed data extraction and was team based, to ensure rigor and consistency. RESULTS: In total, 112 articles covering 51 countries and 9 major worldviews met inclusion criteria. This literature describes culture as it influences perspectives on death and dying, expectations of palliative care, and challenges to providing culturally sensitive care. A key pattern highlighted in articles with respect to the culture and palliative care literature is that culture is invoked in this literature as a sort of catch-all for non-white, non-Christian, indigenous practices, and preferences for palliative care. It is important that humanitarian healthcare providers and organizations aiming to enact their commitment of respect for all persons through attention to potential culturally specific approaches to pain management, suffering, and dying in specific crisis settings do so without reproducing Othering and reductionistic understandings of what culturally sensitive care in humanitarian crises settings involves. SIGNIFICANCE OF RESULTS: This paper clarifies and unpacks the diverse influences of culture in palliative care with the goal of supporting the preparedness and capacity of humanitarian healthcare providers to provide palliative care. In doing so, it aids in thinking through what constitutes culturally sensitive practice when it comes to palliative care needs in humanitarian crises. Providing such care is particularly challenging but also tremendously important given that healthcare providers from diverse cultures are brought together under high stress conditions.

Eye Tracking for Deep Learning Segmentation Using Convolutional Neural Networks.

Deep learning with convolutional neural networks (CNNs) has experienced tremendous growth in multiple healthcare applications and has been shown to have high accuracy in semantic segmentation of medical (e.g., radiology and pathology) images. However, a key barrier in the required training of CNNs is obtaining large-scale and precisely annotated imaging data. We sought to address the lack of annotated data with eye tracking technology. As a proof of principle, our hypothesis was that segmentation masks generated with the help of eye tracking (ET) would be very similar to those rendered by hand annotation (HA). Additionally, our goal was to show that a CNN trained on ET masks would be equivalent to one trained on HA masks, the latter being the current standard approach. Step 1: Screen captures of 19 publicly available radiologic images of assorted structures within various modalities were analyzed. ET and HA masks for all regions of interest (ROIs) were generated from these image datasets. Step 2: Utilizing a similar approach, ET and HA masks for 356 publicly available T1-weighted postcontrast meningioma images were generated. Three hundred six of these image + mask pairs were used to train a CNN with U-net-based architecture. The remaining 50 images were used as the independent test set. Step 1: ET and HA masks for the nonneurological images had an average Dice similarity coefficient (DSC) of 0.86 between each other. Step 2: Meningioma ET and HA masks had an average DSC of 0.85 between each other. After separate training using both approaches, the ET approach performed virtually identically to HA on the test set of 50 images. The former had an area under the curve (AUC) of 0.88, while the latter had AUC of 0.87. ET and HA predictions had trimmed mean DSCs compared to the original HA maps of 0.73 and 0.74, respectively. These trimmed DSCs between ET and HA were found to be statistically equivalent with a p value of 0.015. We have demonstrated that ET can create segmentation masks suitable for deep learning semantic segmentation. Future work will integrate ET to produce masks in a faster, more natural manner that distracts less from typical radiology clinical workflow.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

A Multiparametric Model for Mapping Cellularity in Glioblastoma Using Radiographically Localized Biopsies.

BACKGROUND AND PURPOSE: The complex MR imaging appearance of glioblastoma is a function of underlying histopathologic heterogeneity. A better understanding of these correlations, particularly the influence of infiltrating glioma cells and vasogenic edema on T2 and diffusivity signal in nonenhancing areas, has important implications in the management of these patients. With localized biopsies, the objective of this study was to generate a model capable of predicting cellularity at each voxel within an entire tumor volume as a function of signal intensity, thus providing a means of quantifying tumor infiltration into surrounding brain tissue. MATERIALS AND METHODS: Ninety-one localized biopsies were obtained from 36 patients with glioblastoma. Signal intensities corresponding to these samples were derived from T1-postcontrast subtraction, T2-FLAIR, and ADC sequences by using an automated coregistration algorithm. Cell density was calculated for each specimen by using an automated cell-counting algorithm. Signal intensity was plotted against cell density for each MR image. RESULTS: T2-FLAIR (r = -0.61) and ADC (r = -0.63) sequences were inversely correlated with cell density. T1-postcontrast (r = 0.69) subtraction was directly correlated with cell density. Combining these relationships yielded a multiparametric model with improved correlation (r = 0.74), suggesting that each sequence offers different and complementary information. CONCLUSIONS: Using localized biopsies, we have generated a model that illustrates a quantitative and significant relationship between MR signal and cell density. Projecting this relationship over the entire tumor volume allows mapping of the intratumoral heterogeneity in both the contrast-enhancing tumor core and nonenhancing margins of glioblastoma and may be used to guide extended surgical resection, localized biopsies, and radiation field mapping.

Comparative Effects of CT Imaging Measurement on RECIST End Points and Tumor Growth Kinetics Modeling.

Quantitative assessments of tumor burden and modeling of longitudinal growth could improve phase II oncology trials. To identify obstacles to wider use of quantitative measures we obtained recorded linear tumor measurements from three published lung cancer trials. Model-based parameters of tumor burden change were estimated and compared with similarly sized samples from separate trials. Time-to-tumor growth (TTG) was computed from measurements recorded on case report forms and a second radiologist blinded to the form data. Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival (PFS) measures were perfectly concordant between the original forms data and the blinded radiologist re-evaluation (intraclass correlation coefficient = 1), but these routine interrater differences in the identification and measurement of target lesions were associated with an average 18-week delay (range, -20 to 55 weeks) in TTG (intraclass correlation coefficient = 0.32). To exploit computational metrics for improving statistical power in small clinical trials will require increased precision of tumor burden assessments.

Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. METHODS: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). RESULTS: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. CONCLUSIONS: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

[New in hysteroscopy: hysteroscopic morcellators]. / Nouvelle technique en hystéroscopie : les morcellateurs hystéroscopiques.

A new technology recently appeared for the treatment of endo-uterine pathologies: hysteroscopic morcellators. It seemed to us useful to review this new technology. The morcellator we mostly experiment is the Myosure®, in 14 patients, with a median age of 40.5 years (28-58). The time of procedure went from 5 to 75 min with a median time at 26 min. The median of the total fluid deficit was 300 mL (0-1500 mL). A conversion in traditional resectoscopy happened in 4 cases (29%). This results are not so good as in literature. This is probably bound to one the learning curve but also the type of pathology. For the operative time, all the studies agree that hysteroscopic morcellation is faster than hysteroscopic resection. The quantity of fluid used is also lesser, as the deficit of fluid when the morcellator is used. The percentage of success to remove the pathology is high, close to 100% for the polyps and 92% for the submucous myomas. The indications are the polyps and the submucous myomas type 0 or 1. The morcellation of remnant trophoblastic tissues is also described and seems effective. Others indications, as the removal of uterine septum or cure of uterine synechias, are criticisable. In conclusion, hysteroscopic morcellators are probably a great progress for the cure of the endo-uterine pathologies. They cannot yet concurrence the hysterosopic resectoscopes for the treatment of big submucous myoma or those with a large intramyometrial involvement.

Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis.

Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator-related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator-related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25-30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of 'occult' mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow-up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.

Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.

Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011-2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials.

Semiautomated volumetric measurement on postcontrast MR imaging for analysis of recurrent and residual disease in glioblastoma multiforme.

BACKGROUND AND PURPOSE: A limitation in postoperative monitoring of patients with glioblastoma is the lack of objective measures to quantify residual and recurrent disease. Automated computer-assisted volumetric analysis of contrast-enhancing tissue represents a potential tool to aid the radiologist in following these patients. In this study, we hypothesize that computer-assisted volumetry will show increased precision and speed over conventional 1D and 2D techniques in assessing residual and/or recurrent tumor. MATERIALS AND METHODS: This retrospective study included patients with native glioblastomas with MR imaging performed at 24-48 hours following resection and 2-4 months postoperatively. 1D and 2D measurements were performed by 2 neuroradiologists with Certificates of Added Qualification. Volumetry was performed by using manual segmentation and computer-assisted volumetry, which combines region-based active contours and a level set approach. Tumor response was assessed by using established 1D, 2D, and volumetric standards. Manual and computer-assisted volumetry segmentation times were compared. Interobserver correlation was determined among 1D, 2D, and volumetric techniques. RESULTS: Twenty-nine patients were analyzed. Discrepancy in disease status between 1D and 2D compared with computer-assisted volumetry was 10.3% (3/29) and 17.2% (5/29), respectively. The mean time for segmentation between manual and computer-assisted volumetry techniques was 9.7 minutes and <1 minute, respectively (P < .01). Interobserver correlation was highest for volumetric measurements (0.995; 95% CI, 0.990-0.997) compared with 1D (0.826; 95% CI, 0.695-0.904) and 2D (0.905; 95% CI, 0.828-0.948) measurements. CONCLUSIONS: Computer-assisted volumetry provides a reproducible and faster volumetric assessment of enhancing tumor burden, which has implications for monitoring disease progression and quantification of tumor burden in treatment trials.

Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy.

BACKGROUND: Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients. METHODS: EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model. RESULTS: Increasing IL8(T1) level associated with lower response probability at covariance analysis (P=0.010). Both IL8(T0) (P=0.019) and IL8(T1) (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8(T1) best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8(T1) level<80 pg ml(-1) portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level ≥ 80. CONCLUSION: IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability.

Prognostic aspects of DCE-MRI in recurrent rectal cancer.

OBJECTIVE: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. METHODS: A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. RESULTS: Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. CONCLUSION: K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.

Contrast-enhanced ultrasound monitoring of perfusion changes in hepatic neuroendocrine metastases after systemic versus selective arterial 177Lu/90Y-DOTATOC and 213Bi-DOTATOC radiopeptide therapy.

AIM: Radiopeptide therapy with beta emitter labeled (177)Lu/(90)Y- DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) and more recently also alpha emitting (213)Bi-DOTATOC are promising new treatments for neuroendocrine tumors. No early predictors for treatment response have been recognized and tumor-shrinkage after radiation therapy appears slowly. In some solid tumors a decline in tumor perfusion was found predictive of final treatment response but the gold standard multiphase computed tomography (CT) has a high radiation burden. Therefore we evaluated the ability of contrast-enhanced ultrasound (CEUS) to evaluate tumor perfusion as a response criteria. MATERIALS AND METHODS: 14 patients with hepatic neuroendocrine tumor (NET) metastases were enrolled in the retrospective study. Eleven patients were treated with beta-emitting (177)Lu/(90)Y-DOTATOC, either intravenous (i.v.) (n = 5) or intra-arterial (i.a.) (n = 6) and three patients received alpha-emitting (213)Bi-DOTATOC (i.a.). CEUS and contrast-enhanced CT (CE-CT) were performed before and 3 months after treatment. RESULTS: CE-CT and CEUS presented comparable results in the baseline study and in the assessment of perfusion changes due to the different treatment regimes. A therapy related decrease in tumor perfusion is an early predictor of longterm morphologic response. CONCLUSION: CEUS is available and radiation free technique which showed comparable results for perfusion and diameter of liver metastases compared to CE-CT. Intensity reduction in an arterial phase CEUS can be seen as a positive sign indicating long term tumor response to treatment. Therefore CEUS may be considered as an imaging modality for monitoring early treatment after focal alpha and beta targeted therapy.

Impact of peptide receptor radionuclide therapy on the 68Ga-DOTATOC-PET/CT uptake in normal tissue.

AIM: Positron-emission tomography/computed tomography (PET/CT) with [68Ga]DOTA0-Phe1-Tyr3-octreotide (68Ga-DOTA-TOC) became a standard for somatostatin receptor imaging. We investigated the potential changes of normal tissue uptake in patients with neuroendocrine tumor undergoing peptide receptor radionuclide therapy (PRRT). METHODS: Sixteen patients underwent [68Ga]-DOTA-TOC-PET/CT prior and after 4-6 cycles of PRRT (mean administered activity: 13.8 GBq 90Y+ 9.6 177Lu). The maximum standardized uptake values (SUVmax) of pituitary, thyroid, spleen, liver parenchyma, pancreas, kidneys and adrenals were determined, respectively. RESULTS: SUVmax values prior and after PRRT were in pituitary (5, 56±2,91/ 4,47±2,53), thyroid (2.05±1.11/ 2.49±2.47), spleen (24.95±14.20/20.06±8.53), liver (7.13±3.96/6.62±2.63), pancreas (6.96±1.99/6.83±2.00), kidneys (13.0±3.85/11.31±3.31) and adrenals (9.65± 4.20/7.10±2.86). A comparison of pre- and post treatment values revealed no significant differences (P>0.05) in any of these organs. CONCLUSION: The uptake of [68Ga] DOTA-TOC in normal tissue is not significantly affected by PRRT. This is relevant with regards to therapeutic monitoring were tumor-to-non-tumor ratio seems to be the most robust biomarker.

Increased serum baseline tryptase levels and extensive skin involvement are predictors for the severity of mast cell activation episodes in children with mastocytosis.

BACKGROUND: Despite the good prognosis of pediatric mastocytosis, some patients suffer from severe mast cell (MC) mediator-associated symptoms. The aim of this study was to identify predictors for severe MC mediator release symptoms in children with mastocytosis in the skin (MIS). METHODS: Serum baseline total tryptase (sbT) levels in 111 children with MIS - 80 maculopapular cutaneous mastocytosis/plaque mastocytosis, 22 nodular mastocytosis, and nine diffuse cutaneous mastocytosis - were investigated as a predictive biomarker for the occurrence of MC mediator-related signs and symptoms within the first 18 months after disease onset. RESULTS: Twelve children (11%) who showed extensive cutaneous disease involving >90% of body surface area (BSA) suffered from severe symptoms requiring hospitalization, with (n = 5) or without (n = 6) management in the intensive care unit (ICU) owing to life-threatening complications. The median sbT was significantly (P < 0.001) higher in patients with extensive cutaneous disease vs those with <90% of BSA involved (45.5 vs 5.2 µg/l, respectively), as well as in children with grade 4 (severe mastocytosis-related symptoms requiring emergency therapy and hospitalization) vs those with grade <4 (46.2 vs 5.2 µg/l, respectively). Receiver operating characteristics curve analyses showed that the optimal cutoff s for sbT to predict the need for daily antimediator therapy, hospitalization, and the management in an ICU were 6.6, 15.5, and 30.8 µg/l, respectively (sensitivity and specificity of 77% and 79%, 100% and 95%, and 100% and 96%, respectively). CONCLUSIONS: Increased sbT in association with extensive cutaneous involvement identifies patients at risk for severe MC activation events in pediatric mastocytosis.

Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer.

OBJECTIVE: To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. METHODS: In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K(trans), k(ep), v(e), AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P ≤ 0.05 was considered significant. RESULTS: Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K(trans) (mean 0.5 min(-1) vs. 0.2 min(-1), P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. CONCLUSION: After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. KEY POINTS: Dynamic contrast enhanced (DCE) MRI provides perfusion characteristics of tumours. These objective quantitative measures may be more helpful than subjective imaging alone Some parameters differed markedly between completely responding and incompletely responding rectal cancers. Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers.