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OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy.

ObjectiveOur purpose was to evaluate the role of interstitial brachytherapy in vulvar cancer management.Study designFrom 1985-1992 we performed a retrospective study of patients treated at the University of California, Irvine Medical Center, and Long Beach Memorial Medical Center.ResultsEleven patients received interstitial brachytherapy, with (n = 5) or without (n = 6) external beam radiotherapy, for locally advanced (n = 5) or recurrent (n = 6) vulvar cancer. Local control was achieved in all patients. Ten patients have died of disease at a mean interval of 33 months from the time of treatment, with 9 patients having maintenance of local control at death. One patient is alive without disease after 77 months of follow-up. There were 2 cases of local necrosis (18%) and 1 case of rectovaginal fistula (9%).ConclusionLocal control of advanced vulvar cancer can be achieved with interstitial brachytherapy, with or without external beam radiotherapy. With improved systemic therapy this treatment modality may be used to salvage women with bulky, symptomatic tumors.

A 34-year-old Jehovah's Witness presented with vaginal bleeding and anemia at 23 weeks gestation. She was diagnosed with a FIGO Stage IB2 squamous cell carcinoma of the cervix. The patient refused transfusion of blood products and strongly desired to continue the pregnancy. She was hospitalized and at 33 weeks gestation underwent a Cesarean-radical hysterectomy with measures that minimized blood loss.

A 22-year-old woman carrying twin gestations at 30 weeks presented with preterm labor and a prolapsing cervical mass. Following Cesarean section birth, she was treated with multiagent chemotherapy followed by pelvic radiotherapy for a Stage IIA small cell cancer of the uterine cervix. She is without evidence of disease 5.5 years after diagnosis and is the first reported long-term survivor of a small cell cervical carcinoma diagnosed during pregnancy.

Interleukin-6 (IL-6) is a cytokine that has been implicated as a growth factor in human ovarian carcinoma, yet the in vivo source of IL-6 in patients remains undefined. We measured IL-6 by ELISA in cell-free ascites (CFA) of 19 patients with ovarian carcinoma. IL-6 was detectable in all samples (mean level 3.3 ng/ml). To identify the cellular source of IL-6, we measured this cytokine by ELISA in 24-48 h supernatants of cultured lymphocyte-, macrophage-, and tumor cell-enriched populations purified from three solid ovarian carcinomas by centrifugal elutriation. All cell populations spontaneously released IL-6; however, tumor cells and tumor-associated macrophage released levels of IL-6 that greatly exceeded those released by tumor-associated lymphocytes. Kinetic studies revealed that IL-6 was detectable at 6 h and that levels increased in all cultures examined over a 48 h time course. These data suggest that both tumor and infiltrating host cells may be the source of the high levels of IL-6 found in carcinomatous ascites. Furthermore, although all three cell types examined may contribute to IL-6 production in patients with ovarian carcinoma, tumor cells are perhaps the most clinically significant source.

We examined the in vitro sensitivity of continuous ovarian cancer cells to lymphokine-activated killer T cells (T-LAK) alone or in combination with cytokines. Lymphocyte viability in T-LAK cultures generated from normal donors and ovarian cancer patients declined in the first 2 to 4 days; however, the remaining cells in these cultures maintained a constant rate of proliferation for long periods in vitro. These cells became 90-95% CD3+ TCR+ -alpha/beta T-cells after 7-10 days in culture. The T-LAK cells from normal donors and cancer patients expressed an equal ability to induce lysis of a panel of human target cells (NK-sensitive K562, NK-insensitive RAJI, and two human ovarian tumor lines, SKOV-3 and OVCAR-3), demonstrating that they are nongenetically restricted killers. Preincubation of either the effector or target cells with tumor necrosis factor or interferon-gamma or addition of these cytokines directly to cytolytic assays did not alter the degree of cell lysis in vitro. This is a method for generating large numbers of autologous, cytolytically active T-LAK cells from the blood of ovarian cancer patients that could be employed in adoptive intraperitoneal immunotherapy.

It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors.

It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors.

Four patients with gynecologic tumors recurrent either to the vagina or skin were treated with photoradiation therapy. A cytotoxic effect on the tumor was achieved by injecting hematoporphyrin derivative intravenously followed by exposing the treatment area to light of 630 nm from an argon-ion pumped-dye laser 72 hr later. Of seven tumor sites which were treated, one was completely destroyed, two were diminished in volume by more than 30%, and no response was seen in four. Toxicity was limited to one episode of facial edema and first-degree burn after prolonged exposure to bright artificial light. Phototherapy might be a useful treatment of some gynecologic tumors which recur after standard attempts at control of disease.

Background: Because intrauterine devices (IUD) invoke acute and chronic inflammatory responses in the endometrium, it is possible that prolonged insertion of an IUD could induce endometrial cancer.Methods: We examined the relation between use of an IUD and endometrial cancer risk using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls.Results: A total of 20 (4.9%) cases and 34 (11.4%) controls reported any use of an IUD. After adjustment for potential confounders, IUD use was not associated with an increased risk of endometrial cancer (RR = 0.56 for ever use; 95% CI: 0.3-1.0). Little reduction in risk was observed among women who last used an IUD within 10 years of the index date (RR = 0.84; 95% CI: 0.3-2.4) but risk was decreased among women who used an IUD in the more distant past (RR = 0.45; 95% CI: 0.2-1.0). Risk did not vary consistently with number of years of IUD use or with years since first use. Risk was not increased among women who used inert devices (RR = 0.46; 95% CI: 0.3-3.6) or those who used devices containing copper (RR = 1.08; 95% CI: 0.1-3.6).Conclusion: These data are reassuring in that they do not provide any evidence of an increased risk of endometrial cancer among women who have used IUD. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Jamie F. Chriqui serves as a Council on Education for Public Health site visitor.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: No, there are no competing interests.

Purpose: Youth electronic cigarette (e-cigarette) use remains high in the USA, and advertising is a contributor. The purpose of this study was to identify themes and characteristics of popular e-cigarette companies' advertising after e-cigarette companies became more highly scrutinised in 2018., Methods: Using a systematic, quantitative content analysis, three trained coders coded e-cigarette advertisements from JUUL, Puff Bar, Vuse and Blu from 2019 and 2020. Based on previous work, they coded for: type of advertisement, flavours, promotions, product cues, descriptors, claims, imagery, youth-oriented themes and sensational appeals., Results: Of the 401 e-cigarette advertisements, the majority were emails (38.2%) and Instagram posts (30.9%). Over half (53.6%) showed flavours other than tobacco, with Puff Bar leading the brands (70.2%; p<0.001). The most frequently used product cues were showing the product (51.4%) or packaging (42.4%). The most common claim was being an alternative to smoking (14.2%). The most frequently used imagery was fruit (14.0%), employed most by Puff Bar (p<0.001). The only youth-oriented theme present was humour (4.2%). Positive sensations (eg, good taste, good smell or satisfying; 17.1%) was the most common form of appeal, with Puff Bar using it at the highest frequency (p<0.001)., Conclusion: Even with heightened scrutiny of e-cigarette brands, advertisements still included youth-appealing content such as flavours, fruit imagery and positive sensations. Puff Bar led in all these categories, and it rapidly gained market share after market leader JUUL limited the sales of its flavoured products. Research should continue to monitor the characteristics of e-cigarette advertisements and consider their impact on youth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper considers the responsibilities of the FDA with regard to disseminating information about the benefits and harms of e-cigarettes. Tobacco harm reduction advocates claim that the FDA has been overcautious and has violated ethical obligations by failing to clearly communicate to the public that e-cigarettes are far less harmful than cigarettes. We argue, by contrast, that the FDA's obligations in this arena are more complex than they may appear at first blush. Though the FDA is accountable for informing the public about the health risks and benefits of products it regulates, it also has other roles (and attendant responsibilities) that inform when and how it should disseminate information. In addition to being a knowledge purveyor, it is also a knowledge producer, an advisor to the public, and a practical agent shaping the material conditions in which people make health-related choices. In our view, those other roles call for caution in the way the FDA interprets and communicates the available evidence.

Objectives: Few e-cigarette social media posts are authentic posts to friends; most come from commercially sponsored influencers. Potential disclosure strategies need to be tested to confirm whether users recognize such posts as commercially sponsored., Methods: Between July - August 2019, young adult (ages 16-24; n = 200) participants were recruited to view their native Instagram feed on a laboratory mobile device. Posts from e-cigarette influencers were manipulated to add either #ad or #sponsored while eye tracking software measured visual attention. Participants self-reported their interpretation of the hashtags in open-ended responses. Logistic regression analyses compared recognition of commercial content by condition, and qualitative content analyses summarized the key themes related to the hashtags., Results: The #ad condition had nearly twice the odds of commercial recognition compared to #sponsored (OR = 1.98, CI: 1.14-3.38). Every second of attention paid to the hashtag significantly increased the odds of commercial recognition by 22% (OR: 1.22, CI: 1.00-1.33)., Conclusion: The #ad disclosure attracted visual attention and significantly increased recognition of commercial sponsorship from young social media users. Labeling commercially sponsored content on social media is a promising strategy to better inform users about paid social media influence., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: Disclosures: The authors have no relevant financial disclosures or conflicts of interest.

Objective: Examine trends in e-cigarette use, and Juul use specifically, among U.S. college students., Participants: In 2016, we established a cohort of 529 incoming first-year students to a large Midwestern University. In 2018, these students (now third-years) were re-contacted, and a new sample of 611 incoming first-year students was enrolled., Methods: First-year students in 2016 completed a survey assessing their e-cigarette use; in 2018, first- and second-year students reported on e-cigarette use, and use of Juul specifically., Results: From 2016 to 2018, past 30-day e-cigarette use rose from 5.9% to 27.7%. In 2018, for Juul alone, ever use was above 35% and past 30-day use was above 20% for both cohorts. Juul use did not differ by gender, but was associated with higher socioeconomic status (SES) and being White., Conclusions: Findings present disturbing possibilities for long-term nicotine addiction among the next generation, and underscore the need for a rapid public health response.

Introduction: Tobacco 21 (T21), which sets the minimum legal sales age for tobacco to age 21, is now a national law in the United States. Although T21 is expected to help curb youth tobacco use, its impact may be dampened due to poor retailer compliance. Even within environments where enforcement is strong (ie, compliance checks are conducted with tough sanctions for violations), compliance might vary due to other factors., Aims and Methods: Three studies were conducted in Columbus, OH, where T21 became strongly enforced in 2018. These studies examined how retailer compliance related to features of the neighborhood in which a retailer was located (Study 1), features of the retailer (Study 2), and features of the retail cashier (Study 3)., Results: Study 1 found that, after controlling for race- and age-based factors, retailers located in high (vs. low)-poverty neighborhoods had a lower likelihood of conducting identification (ID) checks. Study 2 found that ID checks were related to whether retailers displayed signage about T21, as required by the city law. Study 3 found that, among cashiers, T21 awareness (which was high) and perceptions about T21 (which were moderate) were not generally related to their retailer's compliance; having (vs. not having) scanners for ID checks was related to a higher likelihood of compliance., Conclusions: These studies emphasize the many, multilevel factors influencing T21 outcomes. Findings also indicate the potential for T21 to widen disparities in tobacco use, indicating the need for strategies to equitably improve T21 compliance., Implications: T21, which sets the minimum legal sales age for all tobacco products to age 21, is now a national law in the United States. Despite optimistic projections about what T21 could achieve, the ultimate impact may be dampened when it is applied in real-world settings. Our project revealed the many, multilevel factors influencing T21 compliance. Findings also indicate the potential for T21 to widen disparities in tobacco use if gaps in compliance persist. Strategies for equitably improving T21 compliance are discussed. This article is of relevance to areas interested in implementing or improving their local T21 enforcement., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Electronic cigarette (e-cigarette) use among adolescents is associated with increased risk of subsequent cigarette smoking initiation in observational research. However, the existing research was not designed to answer causal questions about whether adolescent e-cigarette users would have initiated cigarette smoking if they had never used e-cigarettes. The current study used a causal inference framework to identify whether male adolescent e-cigarette users were at increased risk of initiating cigarette smoking and smokeless tobacco (SLT) use, compared to similar boys who had never used e-cigarettes., Methods: Boys from urban and Appalachian Ohio (N = 1220; ages 11-16 years at enrollment) reported use of e-cigarettes, cigarettes, and SLT at baseline and every six months for two years. A propensity score matching design was implemented, matching one e-cigarette user to two similar e-cigarette non-users. This analysis was completed in 25 multiple imputed datasets to account for missing data. Risk ratios (RRs) comparing risk of initiating cigarettes and SLT for e-cigarette users and nonusers were estimated., Results: Compared to non-users, e-cigarette users were more than twice as likely to later initiate both cigarette smoking (RR = 2.71; 95% CI: 1.89, 3.87) and SLT (RR = 2.42; 95% CI: 1.73, 3.38). They were also more likely to become current (i.e., past 30-day) cigarette smokers (RR = 2.20; 95% CI: 1.33, 3.64) and SLT users (RR = 1.64; 95% CI: 1.01, 2.64)., Conclusions: Adolescent boys who used e-cigarettes had increased risk of later initiating traditional tobacco products when compared to similar boys who had never used e-cigarettes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Relationships between cigarette filter ventilation levels, biomarkers of exposure (BOE) and potential harm (BOPH), and harm perceptions were examined., Methods: Filter ventilation levels in cigarette brands were merged with Wave 1 (2013-2014) Population Assessment of Tobacco Use and Health study. Data were restricted to smokers who reported a usual brand and not regular users of other tobacco products. BOEs included nicotine, tobacco-specific nitrosamines, volatile organic compounds (VOC), and polycyclic aromatic hydrocarbons. BOPHs measured inflammation and oxidative stress. Perceived harm was assessed as self-reported risk of one's usual brand compared with other brands., Results: Filter ventilation ranged from 0.2% to 61.1% ( n = 1,503). Adjusted relationships between filter ventilation and BOE or BOPH were nonsignificant except for VOC N -acetyl-S-(phenyl)-L-cysteine (PHMA) and high-sensitivity C-reactive protein (hsCRP). In pairwise comparisons, PHMA was higher in quartile (Q) 4 (4.23 vs. 3.36 pmol/mg; P = 0.0103) and Q3 (4.48 vs. 3.36 pmol/mg; P = 0.0038) versus Q1 of filter ventilation and hsCRP comparisons were nonsignificant. Adjusted odds of perceiving one's own brand as less harmful was 26.87 (95% confidence interval: 4.31-167.66), 12.55 (3.01-52.32), and 19.18 (3.87-95.02) times higher in the Q2, Q3, and Q4 of filter ventilation compared with Q1 ( P = 0.0037)., Conclusions: Filter ventilation was not associated with BOE or BOPH, yet smokers of higher ventilated cigarettes perceived their brand as less harmful than other brands compared with smokers of lower ventilated cigarettes., Impact: Research to understand the impact of this misperception is needed, and remedial strategies, potentially including a ban on filter ventilation, are recommended., (©2020 American Association for Cancer Research.)

Wound reconstruction surgeries are at high risk for failure. Outpatient wound reconstruction (OWR) describes these procedures performed in the outpatient setting under local anesthesia. The use of closed incision negative pressure therapy (ciNPT) has been shown to protect the incision and help minimize the risk of postoperative complications. To date, this has not been readily adopted in the outpatient setting. The authors report their initial experience with 3 cases of OWR with ciNPT used by the application of disposable negative pressure wound therapy (dNPWT) to the closed, postsurgical incision. The results of these 3 cases were favorable. While more data are needed, the authors believe the use of dNPWT with OWR will help optimize surgical outcomes and serve as an alternative to surgery with acute hospitalization.

Six percent of Americans, including 3 million high schoolers, use e-cigarettes, which contain potentially toxic substances, volatile organic compounds, and metals. We present the first human study on the effects of e-cigarette exposure in the oral cavity. By interrogating both immunoinflammatory responses and microbial functional dynamics, we discovered pathogen overrepresentation, higher virulence signatures, and a brisk proinflammatory signal in clinically healthy e-cigarette users, equivalent to patients with severe periodontitis. Using RNA sequencing and confocal and electron microscopy to validate these findings, we demonstrate that the carbon-rich glycol/glycerol vehicle is an important catalyst in transforming biofilm architecture within 24 hours of exposure. Last, a machine-learning classifier trained on the metagenomic signatures of e-cigarettes identified as e-cigarette users both those individuals who used e-cigarettes to quit smoking, and those who use both e-cigarettes and cigarettes. The present study questions the safety of e-cigarettes and the harm reduction narrative promoted by advertising campaigns., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)