The influence of inhibitors of apoptosis proteins (IAPs) on chronic rhinosinusitis with nasal polyps.

BACKGROUND: Inhibitors of apoptosis proteins (IAPs) modulate the inflammatory process, and may facilitate the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to observe if IAPs were differently expressed between patients with CRSwNP and controls, and to correlate the expression of IAPs with some inflammatory markers, as with the response to nasal corticosteroids in patients with CRSwNP. METHODOLOGY: We obtained nasal biopsies from patients with CRSwNP (n=27) and controls (n=16). qRT-PCR measured the expression of IAPs and caspases, while Luminex assay measured the concentration of cytokines. Unpaired parametric tests and Principal Component Analysis (PCA) were used for statistical analysis. RESULTS: We observed lower expression of IAP genes (XIAP, BIRC2/IAP1, and BIRC3/IAP2) in CRSwNP patients compared to controls, and we identified that patients with bad response to corticosteroids presented lower levels of BIRC2/IAP1, XIAP, BCL2, CASP9, and IL-17, and higher levels of CASP7 and TGF-B. CONCLUSIONS: IAPs expression was downregulated in CRSwNP, and was associated with poorer response to nasal corticosteroids. The present findings suggest the importance of IAPs as a link between environment and the host inflammatory responses, and this pathway could be explored as a potential new target therapy for patients with CRSwNP.

Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

An objective tool to measure the effect of botulinum toxin in blepharospasm and hemifacial spasm.

BACKGROUND AND PURPOSE: It is challenging to assess patients with blepharospasm (BSP) and hemifacial spasm (HFS) as these patients exhibit a wide range of amplitudes of eyelid movements. In order to quantify these movements, a mathematical algorithm, i.e. Fast Fourier Transform, can be employed to convert the signal from the time domain to the frequency domain. The result of this quantification represents the energy generated during the eyelid movements. In order to objectively assess the therapeutic effects of botulinum toxin (BoNT) in these patients, we evaluated the energy generated by the upper eyelid during spontaneous eyelid movements before and after treatment. METHODS: A total of 39 patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinum toxin A injections. A high-speed camera and micro light-emitting diodes were used to register the spontaneous eyelid movements. The result of the quantification obtained using Fast Fourier Transform permitted assessment of the activity associated with the eyelid movements. RESULTS: We studied 78 eyelids. The total energy generated during spontaneous eyelid movements was significantly reduced after treatment in the patients with BSP (P = 0.0018) and on the affected side in the patients with HFS (P = 0.0058). CONCLUSIONS: The assessment of the energy generated by the upper eyelid during spontaneous eyelid movements enabled us to measure the therapeutic effects of BoNT in patients with these conditions. The use of this system could enable customized and fine adjustments to BoNT doses based on each patient's needs.

Three-dimensional analysis of jaw kinematic alterations in patients with chronic TMD - disc displacement with reduction.

The study investigated whether chronic TMD patients with disc displacement with reduction (DDR), performing non-assisted maximum jaw movements, presented any changes in their mandibular kinematics with respect to an age-matched control group. Moreover, it was examined whether jaw kinematics and a valid clinic measure of oro-facial functional status have significant associations. Maximum mouth opening, mandible protrusion and bilateral laterotrusions were performed by 20 patients (18 women, 2 men; age, 18-34 years) and 20 healthy controls (17 women, 3 men; age, 20-31 years). The three-dimensional coordinates of their mandibular interincisor and condylar reference points were recorded by means of an optoelectronic motion analyser and were used to quantitatively assess their range of motion, velocity, symmetry and synchrony. Three functional indices (opening-closing, mandibular rototranslation, laterotrusion - right and left - and protrusion) were devised to summarise subject's overall performance, and their correlation with the outcome of a clinical protocol, the oro-facial myofunctional evaluation with scores (OMES), was investigated. TMD patients were able to reach maximum excursions of jaw movements comparable to healthy subjects' performances. However, their opening and closing mandibular movements were characterised by remarkable asynchrony of condylar translation. They had also reduced jaw closing velocity and asymmetric laterotrusions. The functional indices proved to well summarise the global condition of jaw kinematics, highlighting the presence of alterations in TMD-DDR patients, and were linearly correlated with the oro-facial functional status. The jaw kinematic alterations seem to reflect both oro-facial motor behaviour adaptation and a DDR-related articular impairment.

Screening of basidiomycetes in submerged cultivation based on antioxidant activity.

Submerged cultivation of medicinal basidiomycetes is a reproducible and efficient method of producing mycelia and metabolites. The antioxidant activity indicates its medicinal properties and is an important tool for basidiomycete screening. In this study, we analyzed the production of mycelial biomass and exopolysaccharides and the antioxidant activity of basidiomycete strains in submerged cultivation. Twenty-five strains were used for submerged cultivation in extract malt medium, and the production of mycelial biomass and exopolysaccharides was evaluated. Antioxidant activity was determined using the 1,1-diphenyl-2-picrylhydrazyl method. Among the 25 evaluated strains, Lentinus crinitus produced the highest biomass, reaching 1190 ± 52 mg·L(-1)day(-1); Agaricus subrufescens strains had the highest exopolysaccharide production from 18.96 ± 0.15 to 20.97 ± 2.10 mg L(-1)·day(-1). Additionally, A. subrufescens showed the highest total antioxidant activity, reinforcing the therapeutic potential of this basidiomycete. No significant correlation was found between mycelial biomass or exopolysaccharide production and antioxidant activity; however, the results depended on each species and the strains of the same species. We found large variations in the production of mycelial biomass and exopolysaccharides and in antioxidant activity among different species and among strains of the same species. Thus, evaluating the total antioxidant activity is an important tool for identifying strains with biotechnological potential.

Association of glutathione S-transferase Ω 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-ß), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water.

Human exposure to arsenicals is associated with inflammatory-related diseases including different kinds of cancer as well as non-cancerous diseases like neuro-degenerative diseases, atherosclerosis, hypertension, and diabetes. Interindividual susceptibility has been mainly addressed by evaluating the role of genetic polymorphism in metabolic enzymes in inorganic arsenic (iAs) metabolism. Glutathione S-transferase omega 1-1 (GSTO1-1), which had been associated with iAs metabolism, is also known to participate in inflammatory and apoptotic cellular responses. The polymorphism A140D of GSTO1-1 has been not only associated with distinct urinary profile of arsenic metabolites in populations chronically exposed to iAs in drinking water, but also with higher risk of childhood leukemia and lung disease in non-exposed populations, suggesting that GSTO1-1 involvement in other physiologic processes different from toxics metabolism could be more relevant than is thought. We evaluated the association of the presence of A140D and E208K polymorphisms of GSTO1-1 gene with the expression of genes codifying for proteins involved in the inflammatory and apoptotic response in a human population chronically exposed to iAs through drinking water. A140D polymorphism was associated with higher expression of genes codifying for IL-8 and Apaf-1 mainly in heterozygous individuals, while E208K was associated with higher expression of IL-8 and TGF- gene, in both cases, the association was independently of iAs exposure level; however, the exposure to iAs increased slightly but significantly the influence of A140D and E208K polymorphisms on such genes expression. These results suggest an important role of GSTO1-1 in the inflammatory response and the apoptotic process and indicate that A140D and E208K polymorphisms could increase the risk of developing inflammatory and apoptosis-related diseases in As-exposed populations.

[Towards an early differential diagnosis in autism spectrum disorders and fragile X syndrome. A systematic review]. / Hacia un diagnóstico diferencial temprano en el trastorno del espectro autista y el síndrome de X frágil. Una revisión sistemática.

INTRODUCTION: Nearly 60% of those diagnosed with fragile X syndrome show comorbidity with autism. Thus, there are similarities and differences between both conditions that lead to very different clinical manifestations. However, an early differential diagnosis may help professionals to detect deficits and enhance strengths to apply the best suitable intervention. The purpose of this scoping review was to provide a comprehensive overview of the relation and the differences between autism and fragile X syndrome to orientate diagnosis and intervention. MATERIALS AND METHODS: The research for articles was carried out in PsycInfo, Medline, SCOPUS and Web of Science, including scientific articles published from 2010 to 2020 and children aged 0-6 years. The scoping review followed the PRISMA-ScR criteria. RESULTS: 22 studies were selected. Results were reviewed in terms of structural and morphological changes and cognitive, communicative, social-emotional and sensory-motor skills. CONCLUSIONS: Different growing cerebral patterns are observed in both conditions. Besides, there are early signs from the different developmental areas studied that show comorbidity or allow early differentiation. However, attentional function or repetitive mannerisms, among others, need further research.

TITLE: Hacia un diagnóstico diferencial temprano en el trastorno del espectro autista y el síndrome de X frágil. Una revisión sistemática.Introducción. Aproximadamente el 60% de las personas con síndrome de X frágil también reciben un diagnóstico de trastorno del espectro autista. Entre estos trastornos existen tantas semejanzas como diferencias, que provocan cuadros clínicos distintos, por lo que es importante el diagnóstico diferencial temprano, de cara a conocer los déficits y fortalezas de cada niño y ajustar el tipo de intervención lo mejor posible. El presente estudio tiene como objetivo realizar una aproximación al conocimiento de la relación y las diferencias de ambas condiciones, y contribuir al diagnóstico diferencial y la posterior intervención. Materiales y métodos. Siguiendo el protocolo PRISMA-ScR, se realizaron búsquedas en las bases de datos de PsycInfo, Medline, SCOPUS y Web of Science, incluyendo los artículos científicos empíricos centrados en la etapa de los 0 a los 6 años desde 2010 a 2020. Resultados. Se seleccionaron 22 estudios en los que se trata el desarrollo inicial de estos dos trastornos y su confluencia. Los resultados se reagruparon en función de cambios morfológico-estructurales, y de las áreas cognitivas, comunicativas, socioemocionales y sensoriomotoras. Conclusiones. A nivel morfológico-estructural, parecen existir ciertos patrones de crecimiento cerebral diferenciadores entre estos trastornos. Asimismo, existen ciertas señales de alarma en las distintas áreas del desarrollo que son indicativas de comorbilidad o permiten la discriminación entre patologías, y existe cierto debate en torno a algunas de ellas, como el nivel atencional o los manierismos repetitivos.

Degradation of Methylparaben Using Optimal WO3 Nanostructures: Influence of the Annealing Conditions and Complexing Agent.

In this work, WO3 nanostructures were synthesized with different complexing agents (0.05 M H2O2 and 0.1 M citric acid) and annealing conditions (400 °C, 500 °C and 600 °C) to obtain optimal WO3 nanostructures to use them as a photoanode in the photoelectrochemical (PEC) degradation of an endocrine disruptor chemical. These nanostructures were studied morphologically by a field emission scanning electron microscope. X-ray photoelectron spectroscopy was performed to provide information of the electronic states of the nanostructures. The crystallinity of the samples was observed by a confocal Raman laser microscope and X-ray diffraction. Furthermore, photoelectrochemical measurements (photostability, photoelectrochemical impedance spectroscopy, Mott-Schottky and water-splitting test) were also performed using a solar simulator with AM 1.5 conditions at 100 mW·cm-2. Once the optimal nanostructure was obtained (citric acid 0.01 M at an annealing temperature of 600 °C), the PEC degradation of methylparaben (CO 10 ppm) was carried out. It was followed by ultra-high-performance liquid chromatography and mass spectrometry, which allowed to obtain the concentration of the contaminant during degradation and the identification of degradation intermediates. The optimized nanostructure was proved to be an efficient photocatalyst since the degradation of methylparaben was performed in less than 4 h and the kinetic coefficient of degradation was 0.02 min-1.

Biological effects of sodium fluoride varnishes used in remineralisation of enamel: An in vitro study.

AIM: During the last three decades, fluoride varnishes have been recognised as effective strategies for caries prevention in the young-child population and have contributed to a decrease in its prevalence worldwide. The present study aimed to assess in vitro the level of cytotoxicity and genotoxicity in human primary pulp fibroblasts (DPFs) of two NaF varnishes. MATERIALS AND METHODS: Four experimental assays were carried out (MTS, Mitotracker® system [mitochondrial function and morphology], Live/Dead®, and Comet) to assess the morphology, viability, and genotoxicity of two NaF varnishes (Duraphat® and Clinpro White®, both at two different concentrations). The essays were conducted on cultured pulp fibroblasts, grouped in four experimental and two control groups. Collected data were analysed by one-way ANOVA followed by the post hoc Bonferroni test. RESULTS: Some morphological changes of DPFs could be detected after the NaFVs stimulation. Most DPFs incubated in Duraphat (22.6 mg/L) maintained their morphological characteristics, except for a small decrease in cell size and shorter cytoplasmic projections (filopodia); DPFs treated with Clinpro White Varnish (22.6 mg/L) presented a morphology and size similar to the control group. DPFs exposed to Duraphat (113 mg/L) exhibited significant morphological alterations with considerable cell size increases and DPFs treated with Clinpro White Varnish (113 mg/L) showed a slight cell size increase without noticeable morphological anomalies. The Duraphat (22.6 mg/L) and Clinpro White Varnish (22.6 mg/L) groups promoted 31% and 35% cell proliferation, respectively, whereas DPFs proliferation with Duraphat (113 mg/L) decreased up to 59%, and cell proliferation with Clinpro White Varnish (113 mg/L) was similar to that of control. CONCLUSION: All tested varnishes induced changes in the fibroblastic mitochondria. In general, Duraphat was less biocompatible and caused a change in the number of mitochondria compared to Clinpro White Varnish.

Interstitial pneumonitis associated with sirolimus in liver transplantation: a case report.

Sirolimus is a powerful immunosuppressive drug initially used in kidney transplant patients but now increasingly employed in recipients of other types of solid organ transplants, such as liver, heart, lung, or pancreas. Sirolimus is indicated for rescue therapy and to reduce the toxic side effects of calcineurin inhibitors. However, its use has been associated with an uncommon but important pulmonary toxicity. Reports have described interstitial pneumonitis, bronchiolitis obliterans, organizing pneumonia, and alveolar proteinosis. We present the case of a liver transplant patient with interstitial pneumonitis associated with sirolimus.

Conservation genetics of the giant otter (Pteronura brasiliensis (Zimmerman, 1780)) (Carnivora, Mustelidae).

The giant otter (Pteronura brasiliensis) is an aquatic mammal of the Mustelidae family, endemic to South America. Its original distribution corresponds to the region from the Guyanas to Central-North Argentina, but it is extinct or on the verge of extinction in most of its historical range. Currently, the species is considered endangered by the World Conservation Union (IUCN). Based on its geographic distribution in the South American continent and on some morphological characters, two subspecies were suggested: P. brasiliensis brasiliensis, occurring in the Amazon and Orinoco River Basins, and P. brasiliensis paranensis, in the Paraná and Paraguai River Basins. However, there is no consensus on assuming this subspecies division and no detailed studies have been carried out to elucidate this question. This study aims to evaluate the genetic diversity and population structure of Pteronura brasiliensis along its range in Brazil to check the possibility of the existence of two distinct subspecies using also a reciprocal monophyly criterion. We analyzed the control region, and the Cytochrome b and Cytochrome c Oxidase subunit I genes of the mitochondrial DNA in several giant otter populations from the Amazon and Paraguai River Basins. Analyses have indicated some degree of geographic correlation and a high level of inter-population divergence, although the subspecies division is not highly supported. As we observed strong population structure, we cannot rule out the existence of further divisions shaping the species distribution. The results suggest that a more complex population structure occurs in P. brasiliensis, and the conservation practice should concentrate on preserving all remaining local populations.

Life History of Cochliomyia macellaria (Fabricius, 1775) (Diptera, Calliphoridae), a Blowfly of Medical and Forensic Importance.

The life history traits of blow fly Cochliomyia macellaria (Fabricius, 1775) was studied under semi-controlled laboratory conditions at 29.14°C temperature, 72.53% relative humidity, and 12-h photoperiod. The raw data were analyzed based on the age-stage, two-sex life table, considering the development rates among individuals of both sexes. Cochliomyia macellaria survival rate was 0.43 (♂) and 0.40 (♀), while life expectancy was 17.9 (♂) and 20.9 (♀) days, for adult males and females, respectively. The total fecundity was 681.15 eggs/female, with an average of 3.65 batches/female and 199 eggs/batch. The intrinsic rate of increase (r) was 0.327 days-1, the finite rate of population increase (λ) was 3.35 days-1, the mean generation time (T) was 17.15 days, and the net reproduction rate (R 0 ) was 272.46 offspring/individual. The population parameters found here corroborates that C. macellaria population act as a r selected species under laboratory conditions. Additionally, development data and accumulated degree days (ADD) for each stage of C. macellaria are provided and its implications for the forensic use are discussed.

Primary spinal cord tumors treated with surgery and postoperative irradiation.

Between 1954 and 1979, 37 patients with a primary spinal cord tumor received postoperative irradiation after laminectomy. There were 26 intramedullary and 11 tumors of the conus/cauda equina. The 26 intramedullary tumors were divided as follows: 14 astrocytomas, eight ependymomas, three unbiopsied tumors, and one diffuse histiocytic lymphoma. Of the cauda equina tumors, 10 were ependymomas and one was an astrocytoma. Patients were followed until death or for a minimum of 4 years. The 5- and 10-year actuarial survivals for the entire group were 70 and 58%, respectively. Anatomic location of the tumor was the most important predictor of both survival and neurologic function. Patients with tumors of the cauda equina had superior neurologic function and a significantly better survival than those with tumors at other sites. Recurrent tumor was the cause of death in 82% of the patients dead at the time of analysis. Of the patients alive at the conclusion of the study, 10 were completely normal or had only mild neurologic deficit; the remaining 10 patients were severely disabled. Increasing radiation dose correlated with an increase in tumor control and survival. Of those receiving less than 40 Gy, 77% died of recurrent tumor, while 83% of those who received greater than 40 Gy are alive 4.1 to 28.9 years after treatment.

Locally advanced (noninflammatory) carcinoma of the breast: results and comparison of various treatment modalities.

From 1968-1987 237 women with Stage III, noninflammatory breast cancer were treated with various modalities. Ninety-three (39%) had Stage IIIA tumors, and 144 (61%) had Stage IIIB, noninflammatory tumors (AJC, 1983 staging). Median follow-up was 5.4 years (range 2 to 22 years). No patients were lost to follow-up. Thirty-five patients (15%) were treated with irradiation alone, 27 (11%) with irradiation and adjuvant systemic therapy, 80 (34%) with mastectomy and irradiation, and 95 (40%) with combined mastectomy, irradiation, and systemic therapy. Local/regional control by treatment at 5 and 10 years, respectively, was 31% and 31% for irradiation alone, 47% and 47% for irradiation and systemic therapy, 80% and 80% for irradiation and mastectomy, and 93% and 78% for irradiation, mastectomy, and systemic therapy (p less than .0001). Actuarial disease-free survival by treatment was 19% and 12% for irradiation alone, 25% and 18% for irradiation and systemic therapy, 34% and 20% for irradiation and mastectomy, and 41% and 31% for irradiation, mastectomy, and systemic therapy, at 5 and 10 years, respectively (p = .0001). Patients given systemic therapy and/or irradiation prior to mastectomy had a better local/regional control and DFS and actuarial survival, although not achieving statistical significance (p = 0.10). Of the triple modality group of patients, there were no chest wall failures with chest wall doses greater than 5040 cGy (p = 0.3). There were 40/237 (17%) grade 2 or greater treatment sequelae. The administration of chemotherapy significantly increased complications.

Results of radiotherapy in recurrent endometrial carcinoma: a retrospective analysis of 51 patients.

A retrospective analysis was performed of 51 patients with locoregional recurrence of endometrial carcinoma, treated by radiotherapy between 1959 and 1986. There were 17 patients (33%) with isolated vaginal recurrence, 12 patients (24%) with vaginal recurrence with pelvic extension, 7 patients (14%) with pelvic recurrence only, and 15 patients (29%) with simultaneous locoregional and distant failure. Eighty percent of the recurrences occurred within 3.5 years from primary treatment; time to relapse was shorter in patients with advanced-stage, high-grade malignancy at original diagnosis. Locoregional control was achieved in 18 patients (35%). Complete tumor regression in the vagina, irrespective of extravaginal pelvic disease status or distant metastasis, occurred in 28 of 34 patients with vaginal involvement (82%). The 5- and 10-year overall actuarial survivals for all patients were 18 and 12.5%, respectively. The 5- and 10-year progression-free survivals of patients with isolated vaginal recurrences were 40% and 29%, respectively; the 5-year progression-free survival of patients with vaginal recurrence with pelvic extension was 20%. There were no survivors beyond 1.5 years among patients with pelvic recurrence (p = 0.02). All patients with simultaneous locoregional and distant failure were dead by 3.5 years. Stage at original diagnosis, time to relapse from primary treatment, histologic pattern, and grade of malignancy were prognosticators of survival. Five patients (10%) developed a total of ten radiation-related sequelae.

Childhood cerebellar astrocytomas: is there a role for postoperative irradiation?

Eighty children with astrocytomas of the cerebellum were treated at Washington University Medical Center in St. Louis, Missouri from 1928-1980. The most important predictor of recurrence was completeness of surgical removal. Of 40 patients whose tumors were totally removed, only one recurred (2.5%). Forty cases were subtotally removed and 14 subsequently recurred (35%). Postoperative irradiation did not significantly improve survival in the patients with incompletely excised tumors; however, there was lack of uniformity in the radiation therapy. Although a survival advantage could not be demonstrated, there was a trend toward a lowering of the recurrence rates in patients with subtotally excised solid tumors who received radiation therapy.

External irradiation of epithelial skin cancer.

A total of 339 consecutively treated, biopsy proven squamous and basal cell carcinomas of the skin treated from January 1966 to December 1986 were retrospectively analyzed to determine the patterns of local recurrence. There were 242 basal cell carcinomas, 92 squamous cell carcinomas, and 5 variants of squamous cell carcinoma in various locations. Radiotherapy was the initial treatment modality in 212 patients and 127 were treated after failing initial surgical excision. Lymph nodes were involved in 1/242 patients (.4%) with basal cell carcinoma, 14/92 patients (15%) with initially treated squamous cell carcinoma, and 20/51 (39%) with recurrent squamous cell lesions. Distant metastasis was found in one patient. Superficial X rays were given to 187 patients, electrons to 57 patients, megavoltage photons to 15, and a combination of modalities to the remainder. Overall local tumor control was achieved in 292 of 339 patients (86%), 220 of 242 (91%) with basal cell and 73 of 97 (75%) with squamous cell carcinoma. Tumor control was closely related to the size of the primary lesion. For lesions less than 1 cm tumor control was 97% (86/89) for basal cell and 91% (21/23) for squamous cell carcinoma. For 1 to 5 cm, tumor control was 87% (116/133) for basal cell and 76% (39/51) for squamous cell carcinoma and for lesions greater than 5 cm, the tumor control was 87% (13 of 15) and 56% (9/16), respectively. Tumor control was related to the modality used to treat the patient in spite of stratification of primary lesion size. For superficial X rays, tumor control was 98% (81/83) for lesions less than 1 cm, 93% (94/101) for lesions 1-5 cm and 100% (5/5) for lesions greater than 5 cm. For electrons tumor control was 88% (14/16), 72% (23/32), and 78% (7/9), respectively. For mixed beams tumor control was 90% (9/10), 76% (32/42), and 64% (9/14), respectively, and for 60Co-4 MV X rays, tumor control was 100% (3/3), 67% (6/9), and 33% (1/3), respectively. Cosmesis and complications were analyzed in 261 patients. An excellent or good cosmetic result was found in 92% (239/261) of the patients. There were 8 of 261 patients (3.1%) with fair and 19 of 261 (7.3%) with poor cosmesis. Cosmesis had an inverse relation to the primary lesion size with 97 of 99 patients (98%) with tumors 1 cm or less, 123 of 140 patients (88%) with lesions 1 to 5 cm and 13 of 16 patients (82%) with larger tumors having excellent or good cosmetic results. Cosmesis is also related to treatment modality.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical stage I endometrial cancer: results of adjuvant irradiation and patterns of failure.

A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively from January 1960 through December 1986 with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). Most patients received a preoperative intracavitary insertion (2500-4000 mgh to the uterus with Heyman capsules and tandem and 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 6 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when deep myometrial invasion was present. Occasionally patients were treated with preoperative external beam irradiation (2000 cGy whole pelvis) and intracavitary insertion. The 5-year overall survival for all patients was 84.0% compared to an expected survival of 88.8%. The 5-year progression-free survivals were 92% for FIGO clinical Stage IA and 86% for stage IB (p = 0.12). The dose to the uterine fundus from the preoperative intracavitary insertion was found to have a significant correlation with progression-free survival in patients with grade 3 tumors. Those receiving less than 2500 mgh to the uterine cavity had a 48.9% 5-year progression-free survival compared to 62.7% for 2500-3500 mgh and 87.4% for those receiving greater than 3500 mgh. Analysis of sites of failure showed that less than 1% (7/858) failed in the pelvis alone, 3% (30/858) in the pelvis combined with distant sites, and 7% (60/858) developed distant metastasis only. The lateral pelvic sidewall was the most common site of failure within the pelvis (20/37) and intraperitoneal failures (28/90) and lung (21/90) were the most common sites of distant metastasis. The overall severe (grades 2, 3, and 4) complication rate was 2.7% (23/858).

Regional nodal management and patterns of failure following conservative surgery and radiation therapy for stage I and II breast cancer.

PURPOSE: To determine the incidence, pattern of regional nodal failure, and treatment sequelae as determined by the extent of lymphatic irradiation. METHODS AND MATERIALS: The records of 511 patients with 519 Stage I and II breast cancers treated with breast conserving surgery with or without axillary dissection and irradiation were reviewed. The extent of nodal irradiation was at the discretion of the attending radiation oncologist and varied considerably over the years. Management of the axilla consisted of axillary dissection alone in 351, axillary dissection and supplemental irradiation in 74, irradiation alone in 75, and simply observation in 21 patients. RESULTS: Overall, axillary recurrence was uncommon (1.2%), but was slightly more frequent after irradiation alone (2.7%) than after surgery alone (0.3%), p = 0.14. There was no benefit for supplemental axillary irradiation after an axillary dissection yielding negative or 1 to 3 positive nodes. In the 21 patients in whom the axilla was observed, axillary recurrence was not observed. Supraclavicular failures were rare in women with negative or 1 to 3 positive axillary lymph nodes (0.5%), and not significantly affected by elective irradiation. Internal mammary node recurrence was seen in only one patient, and was not significantly influenced by elective internal mammary irradiation. Both arm and breast edema were significantly more common in women having breast and nodal irradiation than after breast irradiation alone. These sequelae were not influenced significantly by the number of lymph nodes obtained in the axillary dissection specimen. Radiation pneumonitis was seen with increased frequency with more extensive nodal radiotherapy. Pneumonitis was not found to be affected by the administration or sequencing of chemotherapy. CONCLUSION: There is little justification for axillary or supraclavicular irradiation following an axillary dissection which yields negative or minimally involved (1 to 3 positive) lymph nodes. There were too few patients with extensive axillary node metastases (> or = 4 positive) in our series to draw conclusions about the optimal extent of nodal irradiation in this subset. Elective internal mammary lymph node irradiation increases technical complexity, does not appear to be advantageous, and when combined with supraclavicular irradiation places the patient at highest risk for pneumonitis.

Breast conservation therapy for intraductal carcinoma of the breast.

PURPOSE: Between 1979 and 1987, 76 women with 77 ductal carcinomas in-situ of the breast were evaluated by The Radiation Oncology Center after breast conservation surgery. METHODS AND MATERIALS: Seventy breasts (91%) had tylectomy and irradiation and seven breasts (9%) had tylectomy alone. Median follow-up was 4.0 years, with a range of 2-10 years. Fifty patients (65%) had occult lesions discovered by mammography with a median mammographic size of 0.9 cm. The twenty-six patients with presenting symptoms had a median clinical tumor size of 1.95 cm. All patients had local excision of the primary tumor. Of 15 patients who had axillary dissections, one had nodal metastasis. Seventy breasts were irradiated. Seven patients refused radiotherapy. RESULTS: Overall 5-year actuarial survival was 99%; 5-year actuarial disease-free survival was 89%; the 5-year actuarial intramammary tumor control rate for irradiated patients was 93% vs. 57% for patients not irradiated (p < 0.001). Comedocarcinoma had a 5-year actuarial tumor control rate of 75%, 88% in the irradiated group as compared to 98% for all other histologic subtypes of ductal carcinoma in situ (p < 0.03). All six patients with local failure were successfully salvaged by further surgery. Multivariate analysis revealed significant factors in local control to be (a) radiotherapy, (b) comedocarcinoma histology, and (c) menopausal status. CONCLUSIONS: Although the number of patients treated is small, and follow-up time is limited, these early results support the contention that the treatment of ductal carcinoma in situ by excision and irradiation is an acceptable alternative to mastectomy. We urge caution in treating patients with the comedocarcinoma subtype and counsel these patients to have more treatment than excision alone.