Activated B Cells and Plasma Cells Are Resistant to Radiation Therapy.

PURPOSE: B cells play a key role in outcomes of cancer patients and responses to checkpoint blockade immunotherapies. However, the effect of radiation therapy on B cell populations is poorly understood. Here we characterize the effects of radiation on the development, survival, and phenotype of physiological B-cell subsets. METHODS AND MATERIALS: Naïve and immunized tumor bearing and nontumor bearing mice were treated with large-field or focal stereotactic radiation and distinct B-cell subsets of varying developmental stages were analyzed by flow cytometry and real-time reverse transcription polymerase chain reaction. RESULTS: We first report that focal stereotactic radiation is highly superior to large-field radiation at inducing tumor infiltration of B cells, CD8+ T cells, and macrophages. We observed that radiation affects B cell development in the bone marrow, increasing frequencies of early pro-B cells and late pro-B cells while inducing upregulation of programmed cell death protein 1. We then demonstrate that class switched B cells and plasma cells are highly resistant to radiation therapy compared with naïve B cells and upregulate activation markers programmed cell death 1 ligand 2 and major histocompatibility complex class II) after radiation. Mechanistically, radiation upregulates Xbp1 and Bcl6 in plasma cells, conferring radioresistance. Furthermore, using an immunization approach, we demonstrate that radiation enhances activation-induced cytidine deaminase mediated class switching and somatic hypermutation in primed B cells. CONCLUSIONS: These data demonstrate that stereotactic radiation is superior to large-field radiation at inducing infiltration of immune cells into tumors and that plasma cells and class switched B cells are highly resistant to radiation therapy. These results represent the most comprehensive analysis of the effects of radiation on B cells to date and identify novel mechanisms by which radiation modulates immune cells within the tumor microenvironment.

Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2).

PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade ≥3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. RESULTS: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P=.012). The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (n=48), those treated with IG-IMRT (n=35) had a significantly lower incidence of grade ≥3 neutropenia (8.6% vs 27.1%; 2-sided χ2P=.035) and nonsignificantly lower incidence of grade ≥3 leukopenia (25.7% vs 41.7%; P=.13) and any grade ≥3 hematologic toxicity (31.4% vs 43.8%; P=.25). CONCLUSIONS: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia.

Prevalence of mental disorders at admission to the penal justice system in emerging countries: a study from Chile.

BACKGROUND: Previous mental health surveys conducted in prisons within emerging countries recruited samples of all prisoners at any single point in time. However, this sampling strategy results in an overrepresentation of long-term prisoners as compared with those studies recruiting from all admissions over time. This study aimed to assess mental disorders in consecutively admitted prisoners soon after admission, in order to address service needs of people with short-term imprisonments and people at early stages of imprisonment. METHOD: Disorders were assessed in a sample of 229 male and 198 female prisoners, consecutively committed to the penal justice system in Santiago de Chile, using the structured Mini-Neuropsychiatric interview. Prevalence rates were calculated as per cent values. Ninety-five per cent confidence intervals were calculated for the proportions. RESULTS: Illicit drug and/or alcohol use disorders in the year prior to admission were present in 173 (76%) male and 64 (32%) female prisoners. The substances most frequently causing addiction were cocaine-based products in 108 (47%) male and 42 (21%) female prisoners. Current major depression was present in 124 (54%) male and 86 (43%) female prisoners, and current non-affective psychotic disorders in 18 (8%) male and in 10 (5%) female prisoners. High suicidal risk was present in 64 (28%) male prisoners and in 29 (15%) female prisoners. CONCLUSION: When consecutive prisoners are assessed at admission, rates of mental health and substance use disorders were higher than in previous studies in emerging countries that had sampled from all existing prisoners at a time. Affective disorders and suicide risk appear more prevalent than in admission studies conducted in Western high-income countries. Previous research may have systematically underestimated the extent of mental health problems in prisoners, which poses a major public health challenge in emerging countries.

[Rectal cancer surgery in Germany - a 10-year-analysis based on the data of the "Institute of Quality Assurance in Operative Medicine" at the Otto-von-Guericke University Magdeburg]. / Rektumkarzinomchirurgie in Deutschland - eine 10-Jahres-Übersicht auf der Grundlage der Daten des AN-Instituts für Qualitätssicherung in der operativen Medizin gGmbH an der Otto-von-Guericke-Universität Magdeburg.

BACKGROUND: The treatment of rectal cancer has undergone pronounced changes during the last two decades. There has been a significant improvement in local tumour control due to consequent use of neo-adjuvant therapy and total mesorectal excision in cases of distal rectal cancer. The presented analysis examines the realisation of the multimodal therapy for rectal cancer under the conditions of routine patient-centred care over a period of ten years. METHOD: The data acquired in the prospective multicentre observational study "Quality Assurance - Rectal Cancer" from the years 2000 to 2010 were analysed. N = 33,724 patients were documented. The resection rate was 95.2 %. The rate of curative resection was 84.2 %. RESULTS: No change was detected in perioperative total morbidity and lethality during the course of the study. The percentage of patients with neo-adjuvant treatment and curative resection rose from 5.6 % (2000) to 40.5 % (2012). The rate of performed TME in distal rectal cancer rose from 75.2 % (2000) to 95.3 % (2012). For patients who underwent curative resection in the years 2000/2001 the 5-year local recurrence rate was 11.7 %, while it was found to be 4.6 % for patients who were thus treated in the years 2005/2006 (p < 0.001). There was no improvement of total survival. CONCLUSION: While an increase in the use of neo-adjuvant treatment for rectal cancer and the establishment of TME in routine patient-centred care have led to a significant improvement in local tumour control with a constant total morbidity and lethality, there is no detectable influence on the patients' total survival.

[People with mental disorders in East and West Germany: indicators of institutionalized care since reunification]. / Psychisch Kranke in Ost- und Westdeutschland : Indikatoren der Institutionalisierung seit der politischen Wende.

OBJECTIVES: The aim of this study is to compare the historic development of indicators of institutionalized care for the mentally ill in East and West Germany since the political change of 1989. METHODS: Data on numbers of psychiatric beds, prison populations, the occupancy in forensic psychiatric institutions, in rehabilitation services, in supported housing units and involuntary admission rates are presented in historic time lines. Changes were calculated as a percentage. RESULTS: After 1989 general psychiatric bed numbers decreased by 61% and the prison population by 77% in East Germany both from initially higher to then lower rates than in West Germany. Since 1993 there has been an approximation of the numbers in East and West Germany. In both parts of Germany the forensic psychiatric bed numbers, supported housing and rehabilitation capacities have increased. Involuntary admission rates into general psychiatry are on the increase in both parts of Germany. They continue to be 3.3 times higher in West Germany than in East Germany. CONCLUSION: The harmonization of capacities in mental health care institutions between both parts of Germany was realized within a few years after reunification. Continuous differences remain regarding the involuntary admission rates.

Socio-economic status and emotional distress of female Turkish immigrants and native German women living in Berlin.

BACKGROUND: Many immigrants face more economic strains and hardship than non-immigrants. Income inequality and an increasing social gap between immigrants and non-immigrants in Europe warrant further studies on the impact of socioeconomic factors on health in immigrant groups. The purpose of this study was to examine the association of socioeconomic status (SES) and emotional distress in women of Turkish descent and in women of German descent. METHODS AND SUBJECTS: A total of 405 women of German or Turkish descent residing in Berlin were interviewed. Emotional distress was assessed by the General Health Questionnaire-28 (GHQ-28), and SES was examined by level of education, employment status, and income. The associations of emotional distress and SES were estimated in multivariate linear regression analyses. RESULTS: Unemployment was associated with increased levels of emotional distress in all women, with the highest level of distress in the group of unemployed Turkish women. The overall SES level was related to a greater level of emotional distress in Turkish women, but not in German women (-3.2, 95%CI -5.9 - -.5; p=.020 vs. -.8, 95%CI -2.7 - 1.2; p=.431). Further stratified analyses by relationship status revealed that the association of SES and emotional distress only remained significant among single women. CONCLUSION: The impact of socioeconomic hardship appears to be complicated by social roles and expectations related to these. Further in-depth study of the complex nature of the interaction of social roles and socioeconomic position in female Turkish immigrants in Germany is needed to better understand differing risk patterns for emotional distress.

Target localization and toxicity in dose-escalated prostate radiotherapy with image-guided approach using daily planar kilovoltage imaging.

Dose escalation with intensity-modulated radiation therapy (IMRT) for carcinoma of the prostate has augmented the need for accurate prostate localization prior to dose delivery. Daily planar kilovoltage (kV) imaging is a low-dose image-guidance technique that is prevalent among radiation oncologists. However, clinical outcomes evaluating the benefit of daily kV imaging are lacking. The purpose of this study was to report our clinical experience, including prostate motion and gastrointestinal (GI) and genitourinary (GU) toxicities, using this modality. A retrospective analysis of 100 patients treated consecutively between December 2005 and March 2008 with definitive external beam IMRT for T1c-T4 disease were included in this analysis. Prescription doses ranged from 74-78 Gy (median, 76) in 2 Gy fractions and were delivered following daily prostate localization using on-board kV imaging (OBI) to localize gold seed fiducial markers within the prostate. Acute and late toxicities were graded as per the NCI CTCAEv3.0. The median follow-up was 22 months. The magnitude and direction of prostate displacement and daily shifts in three axes are reported. Of note, 9.1% and 12.9% of prostate displacements were ≥ 5 mm in the anterior-posterior and superior-inferior directions, respectively. Acute grade 2 GI and GU events occurred in 11% and 39% of patients, respectively, however no grade 3 or higher acute GI or GU events were observed. Regarding late toxicity, 2% and 17% of patients developed grade 2 toxicities, and similarly no grade 3 or higher events had occurred by last follow-up. Thus, kV imaging detected a substantial amount of inter-fractional displacement and may help reduce toxicity profiles, especially high grade events, by improving the accuracy of dose delivery.

Depression in middle-aged and older first generation migrants in Europe: results from the Survey of Health, Ageing and Retirement in Europe (SHARE).

OBJECTIVE: To determine the prevalence of depression in migrants aged 50 years or older in comparison to residents without a history of migration in 11 European countries. METHODS AND SUBJECTS: The Survey of Health, Ageing and Retirement in Europe (SHARE), a cross-national, multidisciplinary, household-based panel survey using nationally representative probability samples (n=28,517) of 11 European countries of the non-institutionalized population aged 50 years and older. Depression was measured using the EURO-D scale, and odds ratios (OR) were estimated for migration status. Effects of sociodemographic variables, somatic comorbidities, functional impairment, cognitive function, geographic region, and time lived in current country of residence were assessed in multivariate logistic regression analysis. RESULTS: Adjusting for confounds, the OR for depression in migrants was 1.42 (95% CI, 1.28-1.59). The influence of migration status on the prevalence of depression was significantly greater in Northern (OR, 1.85; 95% CI, 1.39-2.46) and Western Europe (OR, 1.38; 95% CI, 1.22-1.57), compared to Southern Europe (OR, 1.16; 95% CI, 0.79-1.70) (p<0.05 for the interaction). CONCLUSION: We found a higher prevalence of depression in first-generation migrants aged 50 years or older, together with relevant geographical variation. This difference was not due to other known predictors of depression in older age.

Development and evaluation of an avian influenza, neuraminidase subtype 1, indirect enzyme-linked immunosorbent assay for poultry using the differentiation of infected from vaccinated animals control strategy.

An indirect enzyme-linked immunosorbent assay (ELISA) was developed using baculovirus, purified, recombinant N1 protein from A/chicken/Indonesia/PA7/2003 (H5N1) virus. The N1-ELISA showed high selectivity for detection of N1 antibodies, with no cross-reactivity with other neuraminidase subtypes, and broad reactivity with sera to N1 subtype isolates from North American and Eurasian lineages. Sensitivity of the N1-ELISA to detect N1 antibodies in turkey sera, collected 3 wk after H1N1 vaccination, was comparable to detection of avian influenza antibodies by the commercial, indirect ELISAs ProFLOK AIV Plus ELISA Kit (Synbiotics, Kansas City, MO) and Avian Influenza Virus Antibody Test Kit (IDEXX, Westbrook, ME). However, 6 wk after vaccination, the Synbiotics ELISA kit performed better than the N1-ELISA and the IDEXX ELISA kit. An evaluation was made of the ability of the N1-ELISA to discriminate vaccinated chickens from subsequently challenged chickens. Two experiments were conducted, chickens were vaccinated with inactivated H5N2 and H5N9 viruses and challenged with highly pathogenic H5N1 virus, and chickens were vaccinated with recombinant poxvirus vaccine encoding H7 and challenged with highly pathogenic H7N1 virus. Serum samples were collected at 14 days postchallenge and tested by hemagglutination inhibition (HI), quantitative neuraminidase inhibition (NI), and N1-ELISA. At 2 days postchallenge, oropharyngeal swabs were collected for virus isolation (VI) to confirm infection. The N1-ELISA was in fair agreement with VI and HI results. Although the N1-ELISA showed a lower sensitivity than the NI assay, it was demonstrated that detection of N1 antibodies by ELISA was an effective and rapid assay to identify exposure to the challenge virus in vaccinated chickens. Therefore, N1-ELISA can facilitate a vaccination strategy with differentiation of infected from vaccinated animals using a neuraminidase heterologous approach.

Uzbekistan: psychiatry in transition.

The center of a national medical identity in Uzbekistan is Abu Ali Ibn Sina born in 980 AD representing Islamic medicine and scientific universalism. Psychiatric institutions were founded under Russian influence starting in the late 19th century. Today, the great challenge in psychiatry is the development of a post-Soviet identity integrating Russian and Islamic traditions.

An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: To investigate the frequency and potential prognostic or predictive value of HER-2 amplification or overexpression in advanced and recurrent endometrial cancers. METHODS: Immunohistochemical staining (IHC; DAKO Herceptest) and fluorescence in situ hybridization (FISH; Vysis Inc. PathVysion DNA Probe Kit) were performed on specimens collected on a randomized Gynecologic Oncology Group (GOG) protocol testing the addition of paclitaxel to doxorubicin/cisplatin. RESULTS: HER-2 overexpression (either 2+ (moderate) or 3+ (strong) immunostaining) and HER-2 gene amplification (a ratio of HER-2 copies to chromosome 17 (CEP17) copies > or = 2) were detected in 44% (104 of 234; 58 were 2+ and 46 were 3+) and 12% (21 of 182) of specimens, respectively. There was a significant increased frequency of overexpression in serous tumors vs. all others (23 of 38, 61% vs. 81 of 196, 41%, respectively, P=0.03). HER-2 amplification also appeared to be more common in serous tumors, but results were not significant (6 of 28, 21% vs. 15 of 141, 11%, P=0.12). There was a significant association between grade and HER-2 amplification among nonserous tumors, with grades 1, 2, and 3 cancers demonstrating 3%, 2%, and 21% amplification, respectively (P=0.003). Neither overexpression nor amplification predicted overall survival (OS) after adjusting for treatment and performance status. CONCLUSIONS: HER-2 amplification was more common in high grade tumors with a trend to being more common in serous tumors. There was no clear evidence for a survival difference or a difference in benefit from the addition of paclitaxel for women with HER-2 amplified or overexpressed tumors; however, power to detect clinically meaningful differences was low.

Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study.

Reduced availability of brainstem serotonin transporters (5-HTT) has been observed in vivo in obsessive-compulsive disorder (OCD). However, results vary and may be influenced by competition with endogenous serotonin. Using positron emission tomography (PET) and [11C]DASB, a specific 5-HTT ligand that showed no competition with serotonin for 5-HTT binding in vitro, we tested the hypothesis that 5-HTT availability is reduced in OCD patients and correlated with OCD severity. METHODS. 5-HTT availability in the thalamus and the midbrain was measured in nine drug-free OCD patients and compared with 19 healthy controls, matched for the individual combination of 5-HTT genotype, gender and smoking status. OCD severity was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS). RESULTS. 5-HTT availability was significantly reduced in the thalamus and midbrain of OCD patients. Age and 5-HTT in the thalamus explained 83% of OCD severity in patients that were drug-free for at least 1 year. CONCLUSION. This PET study confirms a central role of the serotonergic system, particularly the thalamus in the pathogenesis of obsessive compulsive disorder.

Stress susceptibility predicts the severity of immune depression and the failure to combat bacterial infections in chronically stressed mice.

Chronic psychological stress has been suggested to play a role in disorders in which the immune system unexpectedly fails to respond in a protective manner. Chronic combined acoustic and restraint stress compromises the anti-bacterial defense mechanisms of female BALB/c mice. The immunodeficiency is characterized by an apoptotic loss of lymphocytes, reduced ex vivo-inducibility of TNF but increased inducibility of IL10, reduced T-cell proliferation, and impaired phagocyte functions. Stressed mice develop depression-like behavior that was monitored by a stress severity score (SSS). Besides a strain (BALB/c>CBA) and gender (male>female) dependent susceptibility to chronic stress, inbred mice have an individual coping ability. Importantly, the individual SSS strongly correlates with Escherichia coli dissemination after infection as well as with IL10-inducibility and circulating corticosterone levels of each animal.

Paclitaxel, carboplatin, and concomitant radiotherapy for resected patients with high risk head and neck cancer.

Many resected patients with locally advanced head and neck cancer are found on pathological assessment to have high-risk features for recurrence. We thus performed a feasibility trial of post-operative radiotherapy with paclitaxel and carboplatin in high-risk carcinoma of the head and neck. All patients were planned for 6 cycles of weekly paclitaxel (40 mg/m2) and carboplatin (AUC=1) and concomitant radiotherapy, 60 Gy in 6 weeks. The most common side effect was grade 3 and 4 mucositis in 5/6 patients and g-tube placement in 4/6 patients. Five out of 6 patients remain alive without evidence of disease at a mean time of 19 months since completion of therapy. Our pilot study treated 6 postoperative patients. Since 4 of 6 enrolled patients were unable to complete the treatment as prescribed, we conclude that this regimen is not feasible. With an 83% grade 3 or 4 mucositis rate and 67% of patients enrolled requiring feeding tube placement, this regimen is not tolerable.

Spontaneous emission lifetime of a single trapped Ca(+) ion in a high finesse cavity.

We investigate the spontaneous emission lifetime of a single trapped (40)Ca+ ion placed at different positions in the vacuum standing wave inside a high finesse cavity which is stabilized to the atomic transition. The lifetime is measured by quantum state detection after pi-pulse excitation. The result for the natural lifetime of the D(5/2) metastable state of 1161(22) ms agrees, within 1 standard deviation, with the most precise published value. We observe a reduction of the spontaneous emission lifetime of approximately 15% in the node of the vacuum field.

A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors.

OBJECTIVE: To investigate longitudinal cognitive functioning in patients with brain tumor treated with modern highly conformal fractionated partial brain radiation therapy (RT). METHODS: Seventeen (of 22 initial consecutive patients) adults with primarily low-grade brain neoplasms who underwent either biopsy or tumor resection were tested at pre-RT baseline and at 3, 6, 12, and 24 months after baseline. Participants were classified as RT-treated nonprogressors (n = 12) or progressors (n = 3) based on serial follow-up structural imaging. Two patients received surgery only and served as controls to help minimize surgical, practice, test form, or other potential non-RT effects. Serial neuropsychological assessments were conducted using alternate forms of the Selective Reminding Test, 10/36 Spatial Recall Test, and Symbol Digit Modality Test (oral, written) as well as the Shipley Scale (baseline only), Wechsler Adult Intelligence Scale-Revised Digit Span, Trail Making Test, and the Symptom Checklist-90-Revised Global Severity Index scale. RESULTS: There was evidence of subtle attention and memory improvement in RT-treated nonprogressors throughout the 2-year period, with no evidence of cognitive decline. In contrast, patients with disease progression evidenced more substantial decline in memory and attention. CONCLUSIONS: Partial brain fractionated RT was not associated with adverse neuropsychological effects through the first 2 years following therapy.

[Specific behaviour therapy day clinic]. / Die spezifische Verhaltenstherapie-Tagesklinik.

Psychiatric day care has a long tradition. However, psychotherapeutic day care institutions specialising in particular disorders or certain therapeutic approaches are still the exception. A day care unit for behaviour therapy was established at the Clinic for Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf in 1998 as part of a complex inpatient, day care, and outpatient behaviour therapy unit. The immediate and high acceptance by patients and their doctors indicates a strong need of such a treatment setting. We present how this day care unit works and how it differs from the traditional psychiatric day care.

Coupling a single atomic quantum bit to a high finesse optical cavity.

The quadrupole S(1/2)-D(5/2) optical transition of a single trapped Ca+ ion, well suited for encoding a quantum bit of information, is coherently coupled to the standing wave field of a high finesse cavity. The coupling is verified by observing the ion's response to both spatial and temporal variations of the intracavity field. We also achieve deterministic coupling of the cavity mode to the ion's vibrational state by selectively exciting vibrational state-changing transitions and by controlling the position of the ion in the standing wave field with nanometer precision.

A method to assess biochemical activity of liver cells during clinical application of extracorporeal hybrid liver support.

Biochemical activity of a hybrid liver support system based on porcine liver cells was investigated in patients suffering from acute liver failure, coma stage III-IV Patient plasma was drawn systemically and after circulation through the bioreactor at four hour intervals. A method is used that takes into account the rate of plasma flow and the differences in plasma concentration systemically and after circulation through the liver support system to determine the net release or uptake of metabolites such as ammonia, urea and glucose. Urea release (mean 2.28+/-0.37 micromol/h/g cells) and ammonia uptake (mean 0.17+/-0.11 micromol/h/g cells) was seen during treatment, an active role of the system in glucose metabolism was observed. All patients were bridged successfully to liver transplantation.

Outcome and management of pathological stage I endometrial carcinoma patients with involvement of the lower uterine segment.

OBJECTIVE: The objective was to evaluate the clinicopathologic characteristics and outcome of pathologic stage I endometrial carcinoma patients with lower uterine segment (LUS) involvement. METHODS: We retrospectively reviewed the characteristics and outcomes of pathologic stage I endometrial carcinoma patients treated with primary surgery at our institution between 1988 and 1998. The significance of LUS involvement was examined with univariate and multivariate analyses. Median patient follow-up was 37.3 months. RESULTS: Of the 98 cases reviewed, 41 (42%) had LUS involvement. No differences were seen in the clinicopathologic features, extent of surgical staging, or adjuvant therapies between patients with and without LUS involvement. Univariate analysis revealed that grade, lymphovascular invasion (LVI), myometrial invasion (MI), and histology were correlated with recurrence. While the 5-year actuarial disease-free survival was worse in women with LUS involvement (80.3 vs 94.0%) compared to those without, this difference did not reach statistical significance (P = 0.14). Moreover, after controlling for pathologic features in a multivariate model, LUS involvement was not correlated with patient outcome (P = 0.98; hazard rate 0.97; 95% confidence interval 0.24, 4.0). LUS was also not correlated with pelvic recurrence. Of 25 low-risk patients (superficial MI and grade 1-2 disease) with LUS involvement, none recurred in the pelvis following surgery alone. In contrast, pelvic recurrence was common (5/12 or 41.6%) in high-risk patients (deep MI and/or grade 3 tumors) following surgery alone regardless of LUS involvement. CONCLUSION: LUS involvement is common in pathologic stage I endometrial carcinoma but is not correlated with a worse outcome. Moreover, in the absence of adverse pathologic features, LUS involvement is not associated with an increased risk of pelvic recurrence and should not be used as an indication for adjuvant radiation therapy.