RÉSUMÉ
Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase. Three CDK4/6i are approved for the first-line treatment of patients with advanced/metastatic hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) BC in combination with endocrine therapy (ET). Though this has improved the clinical outcomes for survival of BC patients, there is no established standard next-line treatment to tackle drug resistance. Recent studies suggest that CDK4/6i can modulate other distinct effects in both BC and breast stromal compartments, which may provide new insights into aspects of their clinical activity. This review describes the biochemistry of the CDK4/6-Rb-E2F pathway in HR+ BC, then discusses how CDK4/6i can trigger other effects in BC/breast stromal compartments, and finally outlines the mechanisms of CDK4/6i resistance that have emerged in recent preclinical studies and clinical cohorts, emphasizing the impact of these findings on novel therapeutic opportunities in BC.
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Tumeurs du sein , Kinase-4 cycline-dépendante , Kinase-6 cycline-dépendante , Résistance aux médicaments antinéoplasiques , Inhibiteurs de protéines kinases , Humains , Kinase-4 cycline-dépendante/antagonistes et inhibiteurs , Kinase-4 cycline-dépendante/métabolisme , Kinase-6 cycline-dépendante/antagonistes et inhibiteurs , Kinase-6 cycline-dépendante/métabolisme , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Femelle , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/usage thérapeutique , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Animaux , Cycle cellulaire/effets des médicaments et des substances chimiques , Récepteurs des oestrogènes/métabolismeRÉSUMÉ
BACKGROUND: Gastro-esophageal reflux (GORD) following sleeve gastrectomy (SG) is a central challenge, and precise indications for revisional surgery or the physiology have not been precisely defined. We aimed to determine whether OAGB performed for reflux post-SG (1) accelerates gastric emptying half-time, (2) reduces the frequency and severity of reflux events, and (3) improves reflux symptoms. METHODS: We undertook a prospective trial (ACTRN12616001089426). There were 22 participants who underwent measurement before and after revisional surgery with 29 optimal SG (patients with optimal outcome from their primary surgery) as controls. All participants underwent a protocolized nuclear scintigraphy, 24-h pH monitoring, and gastroscopy and completed objective questionnaires. RESULTS: Trial patients were 90.9% female, age 44.4 years. Conversion from SG to OAGB was at a median of 45.2 ± 19.6 months. Scintigraphy showed an increased rate of gastric emptying post-OAGB 34 (IQR 14) vs 24 (IQR 10.3) min, p-value 0.008, with decreased number of reflux events post-prandially (39 (IQR 13) vs 26 (IQR 7), p-value 0.001). This data correlated with the pH analysis; total acid events substantially reduced post-OAGB 58.5 (IQR 88) vs 12 (IQR 9.4) events, p-value 0.017. Endoscopic findings indicated a reduction in incidence of bile stasis 72.7% vs 40.9% post-OAGB, p-value < 0.00010. Post-OAGB, patients experienced less frequent regurgitation (12 ± 4.1 vs. 5.5 ± 3, p-value 0.012) and reflux (37.1 ± 15.7 vs. 16.8 ± 12.6, p-value 0.003). CONCLUSIONS: We found OAGB is an effective treatment for reflux associated with delayed gastric emptying post-SG. The likely mechanisms is by, an increase in the rate of gastric clearance and reduced reflux events and overall esophageal acid exposure. This suggests that some forms of post-SG reflux are driven by slower emptying of the residual stomach and are amenable to treatment with drainage above the incisura.
Sujet(s)
Gastrectomie , Dérivation gastrique , Vidange gastrique , Reflux gastro-oesophagien , Obésité morbide , Humains , Femelle , Reflux gastro-oesophagien/étiologie , Études prospectives , Adulte , Vidange gastrique/physiologie , Mâle , Dérivation gastrique/méthodes , Obésité morbide/chirurgie , Obésité morbide/physiopathologie , Résultat thérapeutique , Gastrectomie/méthodes , Réintervention/statistiques et données numériques , Adulte d'âge moyen , Gastroparésie/étiologie , Gastroparésie/physiopathologie , pHmétrie oesophagienneRÉSUMÉ
Performance testing of gamma cameras and single photon computed tomography/computed tomography (SPECT/CT) systems is not subject to regulatory requirements across states and territories in Australia. Internationally recognised testing standards from organisations such as the National Electrical Manufacturers Association (NEMA) describe methodologies for recommended tests. However, variations exist in suggested quality control (QC) schedules from professional bodies such as the Australia and New Zealand Society of Nuclear Medicine (ANZSNM). In this study, a survey was conducted to benchmark current QC programs across a selected sample of eight standalone and networked Australian public hospitals. Vendor-specific flood-field uniformity (intrinsic or extrinsic/system) verification without photomultiplier (PMT) tuning and CT QC were performed at all sites. Weekly and monthly PMT tuning followed by intrinsic flood-field verifications were performed at most sites. At least half of the sites performed monthly centre of rotation (COR) offset verifications. SPECT/CT alignment calibrations and verifications were undertaken by service engineers at all sites, and periodic verifications were performed by local staff at varying frequencies. Variations were observed for other periodic QC tests such as spatial resolution and planar sensitivity. Similarly, variations were observed for tests specific to whole-body systems and SPECT systems. Most sites checked daily and periodic QC results against pass/fail criteria set by vendors. Additional analyses of the QC results, including trend analysis and periodic reviews, were not common practice. The lack of regulatory requirements is likely to have led to variations in QC tests that are generally either harder to perform or are more labour intensive.
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BACKGROUND: Osteoarticular infections are uncommon and required a multimodal approach for diagnosis. Imaging forms an important component of this multimodal approach. OBJECTIVES: In this narrative review, we describe the different imaging modalities, features of osteoarticular infections present on these imaging approaches and recommendations for which imaging modality should be considered in different types of osteoarticular infections. SOURCES: This narrative review was based on literature review from PubMed and was limited to bacterial infections in adult patients. CONTENT: Imaging modalities include modalities that provide information on the anatomy or radionuclide imaging that provides information about the metabolic activity of the area of interest. Anatomical imaging includes plain radiographs (X-ray), computed tomography, and magnetic resonance imaging. Radionuclide approaches include three-phase bone scintigraphy, gallium scans, white blood cell scintigraphy, and 18F-fluorodeoxy-glucose positron emission tomography. The optimal radiological modality for diagnosis is influenced by multiple factors, including infection location, presence of metalware, timing of infection from any preceding surgery or fracture, antibiotic use, and patient comorbidities. Local availability of scanning modality, tracer supply, technical expertise, and patient access also influences choice. IMPLICATIONS: A collaborative approach with imaging, pathology and clinical input in a multidisciplinary setting is paramount for the diagnosis of osteoarticular infections. Increasing research and improvements in technology will further improve the utility and accuracy of imaging approaches for imaging in osteoarticular infections.
Sujet(s)
Ostéomyélite , Tomographie par émission de positons , Adulte , Humains , Scintigraphie , Tomographie par émission de positons/méthodes , Radiopharmaceutiques , Tomodensitométrie , Imagerie par résonance magnétique , Ostéomyélite/imagerie diagnostiqueRÉSUMÉ
BACKGROUND: Poor weight loss and weight regain are principal challenges following laparoscopic sleeve gastrectomy (LSG). There is a lack of standardised assessments and diagnostic tests to stratify the status post-LSG and determine whether anatomical or physiological problem exists. We aimed to compare nuclear scintigraphy gastric emptying with CT volumetric analysis of sleeve anatomy and determine the impact of anatomy on physiological function and its correlation with weight loss. MATERIALS AND METHODS: Patients greater than 12 months post-LSG were categorised into optimal weight loss (OWL) (n = 29) and poor weight loss groups (PWL) (n = 50). All patients underwent a protocolised nuclear scintigraphy and three-dimensional multi-detector computed tomography (3D-MDCT) gastric volumetry imaging. RESULTS: Post-operative % total weight loss in OWL was 26.2 ± 10.5% vs. 14.2 ± 10.7% in the PWL group (p value < 0.0001). The PWL group had significantly more delayed gastric emptying half-time than OWL (34.1 ± 18.8 vs. 19.5 ± 4.7, p value < 0.0001). Gastric emptying half-time showed statistically significant correlations with weight loss parameters (BMI; r = 0.215, p value 0.048, %EWL; r = - 0.336, p value 0.002 and %TWL; r = - 0.379, p value < 0.001). The median gastric volume on 3D-MDCT did not differ between the OWL (246 (IQR 50) ml) and PWL group (262 (IQR 129.5) ml), p value 0.515. Nuclear scintigraphy gastric emptying half-time was the most highly discriminant measure. A threshold of 21.2 min distinguished OWL from PWL patients with 86.4% sensitivity and 68.4% specificity. CONCLUSION: Nuclear scintigraphy is a potentially highly accurate tool in the functional assessment of sleeve gastrectomy physiology. It appears to perform better as a diagnostic test than volumetric assessment. Gastric volume did not correlate with weight loss outcomes. We have established diagnostic criteria of greater than 21 min to assess sleeve failure, which is linked to suboptimal weight loss outcomes.
Sujet(s)
Laparoscopie , Obésité morbide , Humains , Vidange gastrique , Obésité morbide/chirurgie , Laparoscopie/méthodes , Gastrectomie/méthodes , Perte de poids/physiologie , Tomodensitométrie , Scintigraphie , Tomographie , Résultat thérapeutique , Études rétrospectivesRÉSUMÉ
BACKGROUND: Daily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care generally consists of in-clinic monitoring every 3 months that includes PrEP dispensing, counseling, and screening for HIV and sexually transmitted infections (STIs). However, the optimal frequency for monitoring remains undetermined. Attending a clinic every 3 months for monitoring may be a barrier for PrEP. Online-mediated PrEP care and reduced frequency of monitoring may lower this barrier. OBJECTIVE: The primary objective of this study is to establish the noninferiority of online PrEP care (vs in-clinic care) and monitoring every 6 months (vs every 3 months). The secondary objectives are to (1) examine differences between PrEP care modalities regarding incidences of STIs, HIV infection, and hepatitis C virus infection; retention in PrEP care; intracellular tenofovir-diphosphate concentration; and satisfaction, usability, and acceptability of PrEP care modalities; and (2) evaluate associations of these study outcomes with sociodemographic, behavioral, and psychological characteristics. METHODS: This study is a 2×2 factorial, 4-arm, open-label, multi-center, randomized, controlled, noninferiority trial. The 4 arms are (1) in-clinic monitoring every 3 months, (2) in-clinic monitoring every 6 months, (3) online monitoring every 3 months, and (4) online monitoring every 6 months. The primary outcome is a condomless anal sex act with a casual partner not covered or insufficiently covered by PrEP (ie, "unprotected act") as a proxy for HIV infection risk. Eligible individuals are MSM, and transgender and gender diverse people aged ≥18 years who are eligible for PrEP care at 1 of 4 participating sexual health centers in the Netherlands. The required sample size is 442 participants, and the planned observation time is 24 months. All study participants will receive access to a smartphone app, which contains a diary. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. Participants will complete questionnaires at baseline and 6, 12, 18, and 24 months. Dried blood spots will be collected at 6 and 12 months for assessment of intracellular tenofovir-diphosphate concentration. Incidence rates of unprotected acts will be compared between the online and in-clinic arms, and between the 6-month and 3-month arms. Noninferiority will be concluded if the upper limit of the 2-sided 97.5% CI of the incidence rate ratio is <1.8. RESULTS: The results of the main analysis are expected in 2024. CONCLUSIONS: This trial will demonstrate whether online PrEP care and monitoring every 6 months is noninferior to standard PrEP care in terms of PrEP adherence. If noninferiority is established, these modalities may lower barriers for initiating and continuing PrEP use and potentially reduce the systemic burden for PrEP providers. TRIAL REGISTRATION: ClinicalTrials.gov NCT05093036; https://tinyurl.com/28b8ndvj. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51023.
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The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.
Sujet(s)
Tumeurs , Phosphatidylinositol 3-kinases , Humains , Protéines proto-oncogènes c-akt , Transduction du signal , Sérine-thréonine kinases TOR , Tumeurs/traitement médicamenteux , Tumeurs/génétiqueRÉSUMÉ
PURPOSE: There are significant alterations in gastro-intestinal function, food tolerance, and symptoms following sleeve gastrectomy (SG). These substantially change over the first year, but it is unclear what the underlying physiological basis for these changes is. We examined changes in oesophageal transit and gastric emptying and how these correlate with changes in gastro-intestinal symptoms and food tolerance. MATERIAL AND METHODS: Post-SG patients undertook protocolised nuclear scintigraphy imaging along with a clinical questionnaire at 6 weeks, 6 months, and 12 months. RESULTS: Thirteen patients were studied: mean age (44.8 ± 8.5 years), 76.9% females, pre-operative BMI (46.9 ± 6.7 kg/m2). Post-operative %TWL was 11.9 ± 5.1% (6 weeks) and 32.2 ± 10.1% (12 months), p-value < 0.0001. There was a substantial increase of meal within the proximal stomach; 22.3% (IQR 12%) (6 weeks) vs. 34.2% (IQR 19.7%) (12 months), p = 0.038. Hyper-accelerated transit into the small bowel decreased from 6 weeks 49.6% (IQR 10.8%) to 42.7% (IQR 20.5%) 12 months, p = 0.022. Gastric emptying half-time increased from 6 weeks 19 (IQR 8.5) to 12 months 27 (IQR 11.5) min, p = 0.027. The incidence of deglutitive reflux of semi-solids decreased over time; 46.2% (6 weeks) vs. 18.2% (12 months), p-value < 0.0001. Reflux score of 10.6 ± 7.6 at 6 weeks vs. 3.5 ± 4.4 at 12 months, (p = 0.049) and regurgitation score of 9.9 ± 3.3 at 6 weeks vs. 6.5 ± 1.7, p = 0.021 significantly reduced. CONCLUSIONS: These data demonstrate that there is an increase in the capacity of the proximal gastric sleeve to accommodate substrate over the first year. Gastric emptying remains rapid but reduce over time, correlating with improved food tolerance and reduced reflux symptoms. This is likely the physiological basis for the changes in symptoms and food tolerance observed early post-SG.
Sujet(s)
Reflux gastro-oesophagien , Obésité morbide , Femelle , Humains , Adulte , Adulte d'âge moyen , Mâle , Vidange gastrique/physiologie , Obésité morbide/chirurgie , Reflux gastro-oesophagien/étiologie , Gastrectomie/méthodesRÉSUMÉ
BACKGROUND: Recommendations for surveillance imaging for resected melanoma vary considerably. This study examined the utility of imaging in patients with a high-risk primary melanoma undergoing a protocolized imaging schedule. METHODS: This retrospective study involved data collection regarding imaging, recurrence, and outcome characteristics for patients referred to the Victorian Melanoma Service from January 2016-April 2020 and managed for resected stage IIC or III melanoma. Patients with a T4b tumor who did not undergo a sentinel lymph node biopsy were included (T4bNX). Recurrences were "clinically detected" if they were primarily detected by patient symptoms or physical examination, or 'imaging-detected' if the patient was asymptomatic. Cox regression models including time-varying co-variates were used to assess the impact of imaging-detected versus clinically-detected recurrence on overall survival. RESULTS: Over a median follow-up time of 2.7 years, 199 patients underwent surveillance imaging (T4bNX:22, IIC:33, IIIA:22, IIIB:60, IIIC:61, IIID:1), and 44% (n = 88) experienced disease recurrence. Imaging detected over half (53%) of all recurrences. In adjusted analyses, mortality risk was reduced after an imaging-detected compared to clinically-detected recurrence at any given time from the start of surveillance (hazard ratio 0.25, 95% confidence interval 0.10-0.66, p = .005). CONCLUSION: Our study indicates that routine imaging in the early follow-up period of resected T4bNX, stage IIC and III melanoma plays an important role in the detection of asymptomatic recurrences. Imaging-detected recurrence may be associated with a survival benefit and studies with more prolonged follow-up are required to confirm these findings.
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Mélanome , Tumeurs cutanées , Humains , Tumeurs cutanées/imagerie diagnostique , Tumeurs cutanées/chirurgie , Études rétrospectives , Récidive tumorale locale/imagerie diagnostique , Récidive tumorale locale/chirurgie , Mélanome/imagerie diagnostique , Mélanome/chirurgie , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Stadification tumoraleRÉSUMÉ
BACKGROUND: Intermediate to long-term weight regain is a major challenge following sleeve gastrectomy (SG). Physiological changes that mediate the extent of weight loss remain unclear. We aimed to determine if there were specific esophago-gastric transit and emptying alterations associated with weight regain. MATERIAL AND METHODS: Participants greater than 12 months post-SG were categorized into optimal (n = 29) and poor weight loss (PWL) (n = 72). All patients underwent a liquid contrast barium swallow demonstrating normal post-surgical anatomy and a protocolized nuclear scintigraphy designed specifically to characterize gastric emptying following SG. RESULTS: The %total weight loss in the optimal group was 26.2 ± 10.5 vs. 14.3 ± 8.8% in the PWL group (p = 0.001). Scintigraphy showed PWL had relatively increased gastric emptying half-time (GE 1/2t) 35 (IQR 23) min vs 19 (IQR 5.5) min (p = 0.001). The multivariate regressions delineated GE 1/2t as the best diagnostic measure for PWL (OR 1.16; CI 1.04-1.29, p-value 0.021). The probability of PWL increased by 16% for every 1-min increase above 21 min of GE 1/2t. A threshold of 21 min was found to have 88% sensitivity and 69% specificity predicting poor weight loss. CONCLUSION: Gastric emptying half-times greater than 21 min appear to reliably correlate with poor weight loss following SG. Additionally, further elevations above 21 min in emptying half-time increase the risk of poor weight loss. We have shown nuclear scintigraphy represents a simple and accurate diagnostic tool in patients who experience poor weight loss after SG, provided substantially altered reporting references in interpreting nuclear scintigraphy are applied.
Sujet(s)
Dérivation gastrique , Gastroparésie , Obésité morbide , Humains , Obésité morbide/chirurgie , Gastroparésie/imagerie diagnostique , Gastroparésie/étiologie , Gastrectomie , Perte de poids/physiologie , Prise de poids , Vidange gastriqueRÉSUMÉ
Esophageal cancer (EC), an aggressive and poorly understood disease, is one of the top causes of cancer-related fatalities. GLOBOCAN 2020 reports that there are 544,076 deaths and 604,100 new cases expected worldwide. Even though there are various advancements in treatment procedures, this cancer has been reported as one of the most difficult cancers to cure, and to increase patient survival; treatment targets still need to be established. Nuclear receptors (NRs) are a type of transcription factor, which has a key role in several biological processes such as reproduction, development, cellular differentiation, stress response, immunity, metabolism, lipids, and drugs, and are essential regulators of several diseases, including cancer. Numerous studies have demonstrated the importance of NRs in tumor immunology and proved the well-known roles of multiple NRs in modulating proliferation, differentiation, and apoptosis. There are surplus of studies conducted on NRs and their implications in EC, but only a few studies have demonstrated the diagnostic and prognostic potential of NRs. Therefore, there is still a paucity of the role of NRs and different ways to target them in EC cells to stop them from spreading malignancy. This review emphasizes the significance of NRs in EC by discussing their diverse agonists as well as antagonists and their response to tumor progression. Additionally, we emphasize NRs' potential to serve as a novel therapeutic target and their capacity to treat and prevent EC.
Sujet(s)
Tumeurs de l'oesophage , Récepteurs cytoplasmiques et nucléaires , Différenciation cellulaire , Humains , Lipides , Facteurs de transcriptionRÉSUMÉ
Lung cancer, the second most commonly diagnosed cancer, is the major cause of fatalities worldwide for both men and women, with an estimated 2.2 million new incidences and 1.8 million deaths, according to GLOBOCAN 2020. Although various risk factors for lung cancer pathogenesis have been reported, controlling smoking alone has a significant value as a preventive measure. In spite of decades of extensive research, mechanistic cues and targets need to be profoundly explored to develop potential diagnostics, treatments, and reliable therapies for this disease. Nuclear receptors (NRs) function as transcription factors that control diverse biological processes such as cell growth, differentiation, development, and metabolism. The aberrant expression of NRs has been involved in a variety of disorders, including cancer. Deregulation of distinct NRs in lung cancer has been associated with numerous events, including mutations, epigenetic modifications, and different signaling cascades. Substantial efforts have been made to develop several small molecules as agonists or antagonists directed to target specific NRs for inhibiting tumor cell growth, migration, and invasion and inducing apoptosis in lung cancer, which makes NRs promising candidates for reliable lung cancer therapeutics. The current work focuses on the importance of various NRs in the development and progression of lung cancer and highlights the different small molecules (e.g., agonist or antagonist) that influence NR expression, with the goal of establishing them as viable therapeutics to combat lung cancer.
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In August 2021, a man who has sex with men was diagnosed with HIV-1 infection despite using event-driven pre-exposure prophylaxis for over 2 years with self-reported excellent adherence. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. Background RAM prevalence was two of 164 (1.2%) new HIV diagnoses in Amsterdam (2017-19). We reiterate the need for frequent HIV testing among PrEP users and additional testing in case of symptoms.
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Agents antiVIH , Infections à VIH , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Prophylaxie pré-exposition , Minorités sexuelles , Agents antiVIH/usage thérapeutique , Emtricitabine/usage thérapeutique , Infections à VIH/diagnostic , Infections à VIH/traitement médicamenteux , Infections à VIH/prévention et contrôle , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , Homosexualité masculine , Humains , Mâle , Adhésion au traitement médicamenteux , Pays-Bas/épidémiologie , Autorapport , Ténofovir/usage thérapeutiqueRÉSUMÉ
Acute graft-versus-host disease of the gastrointestinal tract (acute GIT-GVHD) often complicates allogeneic hemopoietic stem cell transplantation (AHSCT). 18F-FDG PET/CT is known to detect active inflammation and may be a useful noninvasive test for acute GIT-GVHD. The objective of this study was to evaluate the diagnostic utility of 18F-FDG PET/CT to noninvasively assess patients with clinically suspected acute GIT-GVHD. Fifty-one AHSCT patients with clinically suspected acute GIT-GVHD prospectively underwent 18F-FDG PET/CT scanning followed by upper and lower GIT endoscopy within 7 d. Endoscopic biopsies of 4 upper GIT and 4 colonic segments were obtained for histology to compare with corresponding quantitative segmental 18F-FDG PET/CT SUVmax Receiver-operating-characteristic curve (ROC) analysis was performed to determine predictive capacity of 18F-FDG PET/CT SUVmax for acute GIT-GVHD. A separate qualitative visual 18F-FDG PET/CT analysis was also performed for comparison. Results: Twenty-three of 51 (45.1%) patients had biopsy-confirmed acute GIT-GVHD, with 19 of 23 (82.6%) having upper GIT and 22 of 22 (100%) colonic involvement. One of 23 patients did not undergo a colonoscopy. GVHD involved the entire colon contiguously in 21 of 22 patients. For quantitative analysis, histology from 4 upper GIT and 4 colonic segments were compared with 18F-FDG PET/CT SUVmax Colonic segments positive for GVHD had a higher SUVmax (4.1 [95% CI, 3.6-4.5]) than did normal colonic segments (2.3 [1.9-2.7], P = 0.006). No difference was demonstrated in upper GIT segments. Quantitative 18F-FDG PET/CT yielded a 69% sensitivity, 57% specificity, 73% negative predictive value, and 59% positive predictive value for the detection of GVHD compared with 70%, 76%, 76%, and 68%, respectively, for qualitative analysis. Conclusion: 18F-FDG PET is a useful noninvasive diagnostic test for acute GIT-GVHD, which when present always involves the colon and usually in its entirety, suggesting colonic biopsy obtained by sigmoidoscopy is adequate for histologic confirmation when acute GIT-GVHD is suspected. Of note, 18F-FDG PET cannot distinguish acute GIT-GVHD from non-GVHD inflammatory changes in the colon.
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Maladie du greffon contre l'hôte , Transplantation de cellules souches hématopoïétiques , Humains , Maladie du greffon contre l'hôte/imagerie diagnostique , Fluorodésoxyglucose F18 , Tomographie par émission de positons couplée à la tomodensitométrie/effets indésirables , Transplantation de cellules souches hématopoïétiques/effets indésirables , Tube digestif/anatomopathologie , Endoscopie gastrointestinale/effets indésirables , Études rétrospectivesRÉSUMÉ
BACKGROUND: The yield of baseline imaging in patients presenting with higher risk primary tumours, at least American Joint Committee on Cancer 8th edition stage IIC or III melanoma, is unclear. METHODS: This retrospective study included patients referred to the Victorian Melanoma Service from January 2017 to April 2020, diagnosed with at least stage IIC or stage III melanoma. Patients with a T4b tumour and no sentinel lymph node biopsy were included as 'T4bNX'. RESULTS: One hundred and sixty-four patients (median age 65 years) with baseline imaging (T4bNX: 19, IIC: 30, IIIA: 21, IIIB: 43, IIIC: 50, IIID: 1) were included. The majority were male (73%), and those with T4bNX melanoma tended to be older (median age 79 years). Distant metastases were detected in 21% (4/19) of T4bNX, 3% (1/30) of stage IIC, 0% (0/21) of stage IIIA, and 6% (6/94) of stages IIIB-D melanoma patients. All stage III patients with distant metastases had palpable lymphadenopathy a presentation. Two patients had brain metastases, both of whom had T4bNX melanoma and synchronous extra-cranial metastases. CONCLUSIONS: Compared to stage IIC, baseline imaging detects higher rates of extra-cranial distant disease in stages IIIB-D and T4bNX melanoma. Intracranial imaging has greater yield in patients with distant extra-cranial disease.
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Mélanome , Tumeurs cutanées , Sujet âgé , Femelle , Humains , Mâle , Mélanome/anatomopathologie , Stadification tumorale , Études rétrospectives , Biopsie de noeud lymphatique sentinelle , Tumeurs cutanées/anatomopathologieRÉSUMÉ
18 F-FDG PET/CT scanning is routinely performed to stage and evaluate the treatment response in many malignancies. Immunotherapy is a rapidly growing treatment option for many cancers, and both clinicians and imaging specialists need to be familiar with 18 F-FDG PET/CT imaging characteristics unique to patients on this type of treatment. In particular, many immune-related adverse events (irAEs) can be detected on 18 F-FDG PET/CT and early accurate identification is critical to reduce treatment related morbidity and incorrect interpretation of malignant disease status. This pictorial essay reviews frequently encountered irAEs in clinical practice and their appearances on 18 F-FDG PET/CT along with a brief discussion on pseudoprogression and hyperprogression.
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Fluorodésoxyglucose F18 , Tumeurs , Humains , Immunothérapie/effets indésirables , Tumeurs/imagerie diagnostique , Tumeurs/thérapie , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Tomographie par émission de positonsRÉSUMÉ
Cucurbitacins constitute a group of cucumber-derived dietary lipids, highly oxidized tetracyclic triterpenoids, with potential medical uses. These compounds are known to interact with a variety of recognized cellular targets to impede the growth of cancer cells. Accumulating evidence has suggested that inhibition of tumor cell growth via induction of apoptosis, cell-cycle arrest, anti-metastasis and anti-angiogenesis are major promising chemo-preventive actions of cucurbitacins. Cucurbitacins may be a potential choice for investigations of synergism with other drugs to reverse cancer cells' treatment resistance. The detailed molecular mechanisms underlying these effects include interactions between cucurbitacins and numerous cellular targets (Bcl-2/Bax, caspases, STAT3, cyclins, NF-κB, COX-2, MMP-9, VEGF/R, etc.) as well as control of a variety of intracellular signal transduction pathways. The current study is focused on the efforts undertaken to find possible molecular targets for cucurbitacins in suppressing diverse malignant processes. The review is distinctive since it presents all potential molecular targets of cucurbitacins in cancer on one common podium.
Sujet(s)
Antinéoplasiques , Tumeurs , Triterpènes , Humains , Cucurbitacines/pharmacologie , Cucurbitacines/usage thérapeutique , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Triterpènes/pharmacologie , Triterpènes/usage thérapeutique , Tumeurs/traitement médicamenteux , Tumeurs/prévention et contrôle , Tumeurs/anatomopathologie , Transduction du signal , ApoptoseRÉSUMÉ
OBJECTIVE: To evaluate the mechanisms associated with reflux events after sleeve gastrectomy (SG). SUMMARY BACKGROUND DATA: Gastro-esophageal reflux (GERD) post-SG is a critical issue due to symptom severity, impact on quality of life, requirement for reoperation, and potential for Barrett esophagus. The pathophysiology is incompletely delineated. METHODS: Post-SG patients, stratified into asymptomatic and symptomatic, underwent protocolized nuclear scintigraphy (n = 83), 24-hour esophageal pH monitoring, and stationary manometry (n = 143) to characterize reflux patterns. Ten patients underwent fasting and postprandial concurrent manometry and pH for detailed analysis of reflux events. RESULTS: Baseline demographics between cohorts were similar: Age 47.2 ± 11.6 versus 44.1 ± 11.3 years ( P = 0.121); females 73.2% versus 90.8% ( P = 0.005); excess weight loss 53.8 ± 28.1% versus 57.4 ± 25.5% ( P = 0.422), follow-up duration 12.3 versus 7.4 months ( P = 0.503). Nuclear scintigraphy delineated bolus-induced deglutitive reflux events (29.6% vs 62.5%, P = 0.005) and postprandial reflux events [4 (IQR2) versus 4 (IQR 3) events, P = 0.356]. Total acid exposure was significantly elevated in the symptomatic population (7.7% vs 3.6%, P < 0.001), especially fasting acid exposure (6.0% vs 1.3%, P < 0.001). pH/manometry analysis demonstrated acute elevations of the gastro-esophageal pressure gradient (>10 mm Hg) underpinned most reflux events. Swallow-induced intragastric hyper-pressur-ization was associated with individual reflux events in most patients (90% in fasting state and 40% postprandial). CONCLUSIONS: We found reflux to be strongly associated with SG and identified 3 unique categories. Bolus-induced deglutitive and postprandial reflux occurred in most patients. Elevated fasting esophageal acid exposure mediated symptoms. Frequent, significant elevation in the gastro-esophageal pressure gradient was the mechanism of reflux and seemed to relate to the noncompliant proximal stomach.
Sujet(s)
Reflux gastro-oesophagien , Qualité de vie , Adulte , pHmétrie oesophagienne , Femelle , Gastrectomie/effets indésirables , Humains , Manométrie , Adulte d'âge moyenRÉSUMÉ
Youth with a migration background are underserved by sexual healthcare. Insight in their experiences is essential to develop tailored services and counter disparities. We explored how youth with a migration background access sexual health information, experience public sexual healthcare, and navigate sexual health in their particular sociocultural contexts. We carried out nine semi-structured interviews and one group interview with twelve young people (18-24) with a migration background in Amsterdam, the Netherlands. Respondents were heterosexually oriented and of various sociocultural backgrounds. Data were analysed using thematic content analysis. Three themes emerged: 'Access to sexual health information', 'Access to primary sexual health care', and 'Strategies for sexual self-care'. Youth sought out information online or from peers, however, conversations mostly focussed on pleasure while risk was often not discussed. Youth valued anonymity when accessing sexual healthcare, and used several strategies, such as staying silent or adhering to values such as 'self-respect', to navigate sexual health within their everyday gendered environments. While these strategies manifested as sources of empowerment, they also resulted in potential vulnerabilities. To counter sexual health disparities among youth with a migration background, public sexual health services should provide culturally safe care and foster participatory collaborations with local stakeholders.
Sujet(s)
Santé sexuelle , Maladies sexuellement transmissibles , Adolescent , Accessibilité des services de santé , Humains , Pays-Bas , Comportement sexuelRÉSUMÉ
BACKGROUND: The clinical utility of fatty meal stimulated cholescintigraphy particularly using a standardized formulation in patients with suspected functional gallbladder disorder has not been extensively studied. We present our seven-year clinical experience using an Ensure plus protocol. METHODS: A retrospective study was performed on patients undergoing stimulated cholescintigraphy using Ensure Plus for evaluation of suspected functional gallbladder disorder. A gallbladder ejection fraction (GBEF) of <33% was considered abnormal. RESULTS: Of the 173 patients evaluated, 57 (33%) had an abnormal GBEF, 112 (65%) had a normal GBEF and 4 (2%) had no gallbladder visualization. Of the 57 patients with an abnormal GBEF, symptom improvement occurred in 30/31 (97%) who underwent cholecystectomy and in 17/26 (65%) who were managed conservatively (p = 0.003). Of the 112 patients with a normal GBEF, symptom improvement occurred in 8/10 (80%) who underwent cholecystectomy and 74/102 (73%) who were managed conservatively (p = 1.000). In the subgroup of 102 patients with a normal GBEF managed conservatively, those without symptomatic improvement had lower GBEFs compared to those with symptomatic improvement (median GBEF 46% versus 57%, p = 0.019). CONCLUSION: Our retrospective results support a clinical role for stimulated cholescintigraphy using Ensure Plus in the evaluation of patients with suspected functional gallbladder disorder. While an abnormal GBEF predicts good surgical outcome, our results suggest that using an absolute GBEF cut off value of <33% may not apply to all patients and hence GBEF results should only be used as an adjunct in the surgical decision-making process.