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Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by 'reader' proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatin-reader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.
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Linhagem da Célula , Cromatina/genética , Proteínas de Ligação a DNA/metabolismo , Mutação com Ganho de Função , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Camundongos , Néfrons/metabolismo , Néfrons/patologia , Fatores de Transcrição/química , Fatores de Transcrição/genéticaRESUMO
OPINION STATEMENT: The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms.
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Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia , Sarcoma/terapia , Sarcoma/diagnóstico , Terapia Combinada/métodos , Estadiamento de Neoplasias , Gerenciamento Clínico , Gradação de Tumores , Resultado do Tratamento , HisterectomiaRESUMO
Background Digital breast tomosynthesis (DBT) has improved the accuracy of mammography, including resolving many breast asymmetries as overlapping breast tissue. The pathologic outcomes of persistent developing asymmetries visualized at DBT are not well established. Purpose To characterize the outcomes and the predictors of malignancy for developing asymmetries visualized at DBT without a sonographic correlate. Materials and Methods This retrospective study included all tomosynthesis-guided biopsies of developing asymmetries performed at a single institution from May 2017 through January 2020. A reader study including three breast imaging radiologists determined interrater agreement and inclusion into the study. Electronic medical records were used to extract patient characteristics, imaging characteristics, and pathologic diagnoses. The Wilcoxon rank sum test, Fisher exact test, and χ2 test were used to analyze correlations of patient and imaging characteristics with likelihood of malignancy. Results The reader study included 95 DBT examinations with moderate interrater reliability (Fleiss κ = 0.45). There was majority reader agreement in 85 of the 95 DBT examinations (89%) of 83 women (median age, 56 years; interquartile range, 47-69 years), and this finalized the study data set. At pathologic examination, most asymmetries (68 of 85, 80%) were benign, with common diagnoses being fibrocystic change (n = 20), stromal fibrosis (n = 10), and fat necrosis (n = 10). The overall malignancy rate was 20% (17 of 85 asymmetries; 95% CI: 12, 29); 15 of the 17 malignancies (88%) were invasive cancers. Malignancies were more common in women with a personal history of breast cancer (35% vs 10%, P = .02). Conclusion In 85 developing asymmetries visualized at digital breast tomosynthesis without a sonographic correlate, there was a 20% (95% CI: 12, 29) malignancy rate, which was higher than the rates of malignancy for a developing asymmetry detected at digital mammography. © RSNA, 2021 See also the editorial by Skaane in this issue.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Biópsia Guiada por Imagem , Mamografia/métodos , Idoso , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
Among 707 women who were recommended to undergo annual diagnostic mammography (DM) surveillance after lumpectomy for breast cancer, 94.9%, 90.4%, and 84.3% of women presented for DM at years 1, 2, and 3 after lumpectomy. A total of 18.8%, 11.0%, and 9.9% of women received additional views at years 1, 2, and 3, compared with the 10.1% institutional screening recall rate. The postlumpectomy year 3 cancer detection rate of 11.7 cancers per 1000 DM examinations was below DM benchmarks. These preliminary findings suggest that returning to screening mammography may be acceptable after 1 year of postlumpectomy DM follow-up.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Detecção Precoce de Câncer/métodos , Mamografia , Mastectomia Segmentar , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos RetrospectivosRESUMO
PURPOSE: This comparative survey of surgical practice patterns between 2010 and 2020 aims to elicit trends in practice patterns for transsphenoidal surgery and to identify areas for improvement. METHODS: Web-based surveys were sent to the International Society of Pituitary Surgeons via a membership listserv in 2010 and 2020. These 33-item surveys collected information on demographics, surgical approach, perceived advantages and disadvantages, and recommendations for improvements. Statistical analyses were conducted using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables. RESULTS: There were 51 respondents in 2010 and 82 respondents in 2020. The majority were full-time academic surgeons from the United States or Europe. Preference for a purely endoscopic technique increased from 43% in 2010 to 87% in 2020. Preference for routinely working with an otolaryngologist or second neurosurgeon increased from 35 to 51%. Most surgeons (74%) reported that they were more likely to achieve a greater extent of resection with the endoscope, though 51% noted increased operating time. The most commonly rated advantage (34%) of endoscopic TSS was fewer postoperative nasoseptal perforations; the most commonly (34%) rated disadvantage was more postoperative complications, including cerebrospinal fluid leak. Respondents were divided on whether microscopic TSS should continue to be taught in residency. Many (32%) advocated for improved endoscopic instrumentation and team training. CONCLUSION: Endoscopic TSS is now the clearly preferred method for surgery amongst a cohort of higher-volume academic neurosurgeons. This trend is likely to continue, and this provides guidelines for future training.
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Endoscopia/métodos , Microcirurgia/métodos , Endoscopia/normas , Feminino , Humanos , Masculino , Microcirurgia/normas , Neurocirurgiões/normas , Neurocirurgiões/estatística & dados numéricos , Hipófise/cirurgia , Neoplasias Hipofisárias/cirurgia , Inquéritos e QuestionáriosRESUMO
We characterized a case of neonatal conjunctivitis in New York, USA, caused by Neisseria meningitidis by using whole-genome sequencing. The case was a rare occurrence, and the isolate obtained belonged to an emerging clade (N. meningitidis US nongroupable urethritis) associated with an increase in cases of urethritis since 2015.
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Conjuntivite/epidemiologia , Conjuntivite/microbiologia , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Neisseria meningitidis , Conjuntivite/história , Feminino , Genoma Bacteriano , História do Século XXI , Humanos , Recém-Nascido , Masculino , Infecções Meningocócicas/história , New York/epidemiologia , Filogenia , Polimorfismo de Nucleotídeo Único , Uretrite/epidemiologia , Uretrite/microbiologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Research shows that adults with intellectual and developmental disabilities (IDD) increasingly outlive caregivers, who often struggle to plan for the future and have little support and knowledge surrounding long-term care planning. METHODS: The study team conducted interviews with parents and siblings of adults with IDD and performed qualitative coding using a modified grounded theory to explore domains of future planning and identify barriers and facilitators. RESULTS: Themes from the interviews revealed seven major domains of future planning that should be considered by caregivers of adults with IDD. These domains are housing, legal planning, identification of primary caregiver(s), financial planning, day-to-day care, medical management and transportation. Approaches to planning within each domain varied greatly. CONCLUSIONS: The study team dentified the domain of "identification of primary caregiver(s)" as potentially the most important step for caregivers when planning for the future, but also observed that the domains identified are significantly interrelated and should be considered together.
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Planejamento Antecipado de Cuidados , Cuidadores , Deficiências do Desenvolvimento/enfermagem , Deficiência Intelectual/enfermagem , Pais , Irmãos , Adolescente , Adulto , Idoso , Feminino , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
This study uses data from electronic health records to examine the rate of tubal sterilization requests in 3 periods before and after the US Supreme Court's 2022 Dobbs v Jackson Women's Health Organization decision, compared with the same periods in 2019 and 2021, at a single institution in Michigan.
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Aborto Induzido , Esterilização Tubária , Decisões da Suprema Corte , Feminino , Humanos , Gravidez , Aborto Induzido/legislação & jurisprudência , Aborto Legal/legislação & jurisprudência , Estados UnidosRESUMO
OBJECTIVE: The objective of this study was to estimate the economic consequences of expanding options for early pregnancy loss (EPL) treatment beyond expectant management and operating room surgical evacuation (usual care). STUDY DESIGN: We constructed a decision model using a hypothetical cohort of women undergoing EPL management within a 30 day horizon. Treatment options under the usual care arm include expectant management and surgical uterine evacuation in an operating room (OR). Treatment options under the expanded care arm included all evidence-based safe and effective treatment options for EPL: expectant management, misoprostol treatment, surgical uterine evacuation in an office setting, and surgical uterine evacuation in an OR. Probabilities of entering various treatment pathways were based on previously published observational studies. RESULTS: The cost per case was US $241.29 lower for women undergoing treatment in the expanded care model as compared with the usual care model (US $1033.29 per case vs US $1274.58 per case, expanded care and usual care, respectively). The model was the most sensitive to the failure rate of the expectant management arm, the cost of the OR surgical procedure, the proportion of women undergoing an OR surgical procedure under usual care, and the additional cost per patient associated with implementing and using the expanded care model. CONCLUSION: This study demonstrates that expanding women's treatment options for EPL beyond what is typically available can result in lower direct medical expenditures.
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Abortivos não Esteroides/economia , Aborto Espontâneo/economia , Procedimentos Cirúrgicos Ambulatórios/economia , Dilatação e Curetagem/economia , Misoprostol/economia , Abortivos não Esteroides/uso terapêutico , Aborto Espontâneo/terapia , Dilatação e Curetagem/métodos , Medicina Baseada em Evidências/economia , Feminino , Custos de Cuidados de Saúde , Humanos , Misoprostol/uso terapêutico , Modelos Econômicos , Salas Cirúrgicas/economia , Gravidez , Primeiro Trimestre da Gravidez , Conduta ExpectanteRESUMO
INTRODUCTION: Interprofessional experiences provide critical exposure to collaborative health care teams, yet medical students often lack this experience during clinical clerkships. We created a labor and delivery triage rotation exclusively staffed by certified nurse-midwives in the obstetrics and gynecology clerkship to address this gap. We sought to evaluate the clinical learning experiences of medical students rotating on this midwife-supervised collaborative team. METHODS: Between 2018 and 2020, we electronically sent all medical students an evaluation after each required clerkship. Our primary outcome was the quality of teaching score, as defined by level of agreement on a 5-point Likert scale with a statement regarding teaching quality. A secondary outcome evaluated scores from the National Board of Medical Examiners (NBME) Obstetrics and Gynecology subject examination taken by all students at the end of the rotation. Evaluations and assessments were compared between students rotating on labor and delivery triage and those who did not. Evaluation comments from students rotating on labor and delivery triage were collated to identify common themes. RESULTS: Of 374 students, 370 (98.9%) completed the end-of-clerkship course evaluation and 312 (83.4%) completed teaching evaluations. Sixty-seven students (17.9%) rotated in labor and delivery triage; of these, 52 (77.6%) completed both the course and triage rotation evaluations. There were no differences in the mean quality of teaching scores (3.9 ± 1.2 versus 3.8 ± 1.2, p = 0.54) or in NBME Obstetrics and Gynecology subject examination scores between students rotating in labor and delivery triage compared to all other rotations (79.9% ± 7.2% vs 80.2% ± 7.8%, P = 0.436). Comments from teaching evaluations highlighted student exposure to the midwifery philosophy of care model. DISCUSSION: This work demonstrates the feasibility and benefits of this midwife-led authentic interprofessional collaborative experience for medical students. This model can serve as an example of how to implement and evaluate interprofessional collaboration experiences in the clinical setting.
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Estágio Clínico , Comportamento Cooperativo , Ginecologia , Relações Interprofissionais , Tocologia , Enfermeiros Obstétricos , Obstetrícia , Estudantes de Medicina , Humanos , Estágio Clínico/métodos , Ginecologia/educação , Obstetrícia/educação , Enfermeiros Obstétricos/educação , Feminino , Tocologia/educação , Gravidez , Equipe de Assistência ao Paciente , Educação Interprofissional/métodos , TriagemRESUMO
Improvement in symptom severity and quality of life (QoL) are critical concerns for women with fibroids as they evaluate treatment options. This systematic review analyzed available evidence regarding minimally invasive approaches to fibroid treatment and compared validated QoL and fibroid-associated symptom scores before and after treatment. A comprehensive search was conducted using PubMed, Embase, Cochrane Library, and Scopus from January 1990 to July 2020. English-language publications were included if they evaluated associations between minimally invasive approaches to fibroid treatment and QoL or fibroid-associated symptoms, and they used validated questionnaires before and after treatment. QoL or fibroid-associated symptom scores were compared and summarized for each minimally invasive approach. Thirty-seven studies were ultimately included in this review: 26 evaluating individual approaches and 11 which were comparative studies of minimally invasive approaches and surgical interventions. Radiofrequency ablation (RFA) and ultrasound-guided sclerotherapy (USGS) significantly improved overall QoL. Uterine artery embolization (UAE) and ultrasound-guided high-intensity frequency ultrasound (US-HIFU) improved overall QoL to a similar extent as surgical interventions. Twenty-eight studies assessed fibroid-associated symptoms with the Uterine Fibroid Symptoms Quality of Life Questionnaire (UFS-QoL). UAE, magnetic resonance imaging-guided high-intensity frequency ultrasound (MR-HIFU), US-HIFU, RFA, and percutaneous microwave ablation (PMWA) significantly decreased Symptom Severity Score by a range of 21 to 39 points (out of 100) at 6 months. Minimally invasive approaches to treat fibroids were effective alternatives to surgical interventions for improving quality of life, fibroid-associated symptoms, and pain. Outcomes among minimally invasive approaches were similar, presenting patients with numerous options for fibroid treatment.
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Leiomioma , Neoplasias Uterinas , Humanos , Feminino , Qualidade de Vida , Neoplasias Uterinas/cirurgia , Resultado do Tratamento , Leiomioma/cirurgia , Leiomioma/patologia , UltrassonografiaRESUMO
OBJECTIVE: The endocannabinoid system is involved in pain perception and inflammation. Cannabis contains delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are cannabinoids that bind to endocannabinoid system receptors. A fatty acid amide called palmitoylethanolamide (PEA) enhances endogenous cannabinoids. Given that use of medical cannabis is increasing, we sought to characterize patterns of cannabis use for gynecologic pain and its effectiveness as an analgesic. DATA SOURCES: We searched PubMed, EMBASE, Scopus, Cochrane, and ClinicalTrials.gov using terms for "woman," "cannabis," and "pain" or "pelvic pain" or "endometriosis" or "bladder pain" or "cancer." The search was restricted to English-language articles published between January 1990 and April 2021 and excluded animal studies. METHODS OF STUDY SELECTION: The initial search yielded 5,189 articles with 3,822 unique citations. Studies were included if they evaluated nonpregnant adult women who used cannabinoids for gynecologic pain conditions (eg, chronic pelvic pain, vulvodynia, endometriosis, interstitial cystitis, malignancy). Study types included were randomized controlled trials (RCTs), cohort studies, and cross-sectional studies. Covidence systematic review software was used. TABULATION, INTEGRATION, AND RESULTS: Fifty-nine studies were considered for full review, and 16 met inclusion criteria. Prevalence of cannabis use ranged from 13% to 27%. Most women ingested or inhaled cannabis and used cannabis multiple times per week, with dosages of THC and CBD up to 70 mg and 2,000 mg, respectively. Sixty-one to 95.5% reported pain relief. All six prospective cohort studies and one RCT of PEA-combination medications reported significant pain relief, and the average decrease in pain after 3 months of treatment was 3.35±1.39 on the 10-point visual analog scale. However, one fatty acid amide enzyme inhibitor RCT did not show pain reduction. CONCLUSION: Survey data showed that most women reported that cannabis improved pain from numerous gynecologic conditions. Cohort studies and an RCT using PEA-combination medications reported pain reduction. However, interpretation of the studies is limited due to varying cannabis formulations, delivery methods, and dosages that preclude a definitive statement about cannabis for gynecologic pain relief. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021248057.
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Doenças dos Genitais Femininos/terapia , Maconha Medicinal/uso terapêutico , Manejo da Dor , Feminino , HumanosRESUMO
BACKGROUND: The COVID-19 pandemic disrupted medical care in the US, leading to a significant drop in utilization of some types of health services. We sought to quantify how the pandemic influenced obstetrics and gynecology care at two large health care organizations. MATERIALS AND METHODS: Comparing 2020 to 2019, we quantified changes to obstetrics and gynecology care at two large health care organizations in the United States, Allegheny Health Network (in western Pennsylvania) and Johns Hopkins University (in Maryland). The analysis considered the numbers of surgical encounters, in-person visits, and telemedicine visits. For each system, we quantified temporal changes in surgical volume, in-person and telemedicine visits, and financial impact related to professional fee revenues. We used segmented regression to evaluate longitudinal effects. RESULTS: At both institutions, the volume of care was similar in the first few months of 2020 compared to 2019 but dropped precipitously in March 2020. From April to June 2020, surgical volumes were 67% of the same period in 2019 at Allegheny Health and 48% of the same period in 2019 at Johns Hopkins. During that same interval, televisits accounted for approximately 21% of all ambulatory care at both institutions. Although surgical and ambulatory volumes recovered in the second half of 2020, annual surgical volumes in 2020 were significantly lower than 2019 at both institutions (p<0.05) and 2020 ambulatory volumes remained significantly lower at Johns Hopkins (p = .0006). Overall, revenues in 2020 were 91% of 2019 revenues for both institutions. CONCLUSIONS: Obstetrical and gynecologic ambulatory visits and gynecologic surgeries were sharply reduced during the COVID-19 pandemic. Although care volumes returned to 2019 levels in late 2020, we observed an overall reduction in the volume of care provided and a 9% reduction in professional revenue for both institutions.
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COVID-19 , Telemedicina , Assistência Ambulatorial , Instituições de Assistência Ambulatorial , COVID-19/epidemiologia , Feminino , Humanos , Pandemias , Gravidez , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Traumatic brain injury (TBI) can precipitate new-onset psychiatric symptoms or worsen existing psychiatric conditions. To elucidate specific mechanisms for this interaction, neuroimaging is often used to study both psychiatric conditions and TBI. This systematic review aims to synthesize the existing literature of neuroimaging findings among patients with anxiety after TBI. METHODS: We conducted a Preferred Reporting Items for Systematic Review and Meta-Analyses-compliant literature search via PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases before May, 2019. We included studies that clearly defined TBI, measured syndromal anxiety as a primary outcome, and statistically analyzed the relationship between neuroimaging findings and anxiety symptoms. RESULTS: A total of 5982 articles were retrieved from the systematic search, of which 65 studied anxiety and 13 met eligibility criteria. These studies were published between 2004 and 2017, collectively analyzing 764 participants comprised of 470 patients with TBI and 294 non-TBI controls. Imaging modalities used included magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, electroencephalogram, magnetic resonance spectrometry, and magnetoencephalography. Eight of 13 studies presented at least one significant finding and together reflect a complex set of changes that lead to anxiety in the setting of TBI. The left cingulate gyrus in particular was found to be significant in 2 studies using different imaging modalities. Two studies also revealed perturbances in functional connectivity within the default mode network. CONCLUSIONS: This is the first systemic review of neuroimaging changes associated with anxiety after TBI, which implicated multiple brain structures and circuits, such as the default mode network. Future research with consistent, rigorous measurements of TBI and syndromal anxiety, as well as attention to control groups, previous TBIs, and time interval between TBI and neuroimaging, are warranted. By understanding neuroimaging correlates of psychiatric symptoms, this work could inform future post-TBI screening and surveillance, preventative efforts, and early interventions to improve neuropsychiatric outcomes.
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Lesões Encefálicas Traumáticas , Imagem de Tensor de Difusão , Ansiedade/diagnóstico por imagem , Ansiedade/etiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Neuroimagem/métodosRESUMO
â¢A subset of patients with uterine carcinosarcoma will have ER/PR positive disease.â¢Hormone receptor expression may serve as a therapeutic target in high-grade endometrial tumors.â¢Hormonal therapy and SBRT may have benefit in the management of recurrent uterine carcinosarcoma.
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PURPOSE: Pleomorphic adenoma is a benign salivary tumor that may recur multifocally. In case series, the benefit of radiation therapy (RT) for recurrent pleomorphic adenoma remains unclear. We hypothesized that the combination of surgery and adjuvant RT reduces risk of subsequent recurrence compared with surgery alone for recurrent pleomorphic adenoma. METHODS AND MATERIALS: Patients who received diagnoses of recurrent pleomorphic adenoma between 1980 and 2016 were identified using an institutional pathology database. Medical records were retrospectively reviewed to determine clinical, operative, pathologic, and imaging characteristics. Kaplan-Meier methods were used to estimate local control after surgery, stratified by completeness of resection and receipt of adjuvant RT. The association of variables with risk of subsequent local recurrence was analyzed using Cox proportional hazards model, and variance estimates were calculated to account for multiple recurrences in the same patient. Toxicities were prospectively recorded in a departmental database. RESULTS: A total of 49 patients presented with at least 1 recurrence, of which 28 were managed with surgery alone, and 21 were treated with surgery and RT. The median follow-up time after the initial recurrence was 48 months (range, 6-531 months). There were 35 subsequent recurrences; 34 after surgery alone and only 1 after surgery with RT. On multivariate analysis, adjuvant RT was associated with decreased risk of recurrence (hazard ratio, 0.09; 95% confidence interval, 0.02-0.41, P = .002), whereas increasing number of prior recurrences was associated with increased risk (hazard ratio, 1.23; 95% confidence interval, 1.13-1.35, P < .001). Common toxicities of RT included dermatitis, xerostomia, and mucositis. CONCLUSIONS: For patients with recurrent pleomorphic adenoma, the addition of adjuvant RT after surgery is associated with a significant decrease in risk of subsequent tumor recurrence.
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BACKGROUND/AIMS: While it is well established that acupuncture relieves somatic pain, its therapeutic effect on visceral pain such as irritable bowel syndrome (IBS) is unclear. We evaluated the effect of acupuncture in treating visceral hyperalgesia in an animal model. METHODS: Sprague-Dawley rats (n = 8 per group) with prior neonatal maternal separation stress were randomly allocated to receive 3-day treatment of either electroacupuncture (EA) or sham acupuncture at acupoint ST-36. Another group of rats without prior maternal separation was included as non-handled controls. Colorectal distension was performed on the day after acupuncture treatment. The 3 groups were compared for pain threshold as determined by abdominal withdrawal reflex and visceromotor response as measured by electromyogram. Colon, spinal cord, and brainstem were sampled for topographic distribution and quantitative assessment of serotonin and Fos expression by immunohistochemistry. RESULTS: Rats in EA group had significantly higher pain threshold compared to those in sham acpuncture group (25.0 +/- 5.7 mmHg vs 18.7 +/- 5.2 mmHg, p = 0.01) and it was comparable with that of non-handled treatment naïve controls (29.4 +/- 9.3 mmHg, p = 0.28). They also had lower visceromotor response as measured by electromyogram compared to those received sham acupuncture at all colorectal distension pressures. EA significantly suppressed Fos expression in doral raphe nuclei of brainstem, superficial dorsal horn of spinal cord and colonic epithelium but suppressed 5-HT expression only in brainstem and spinal cord. CONCLUSIONS: Electro acupuncture attenuates visceral hyperlagesia through down-regulation of central serotonergic activities in the brain-gut axis.