The efficacy of topical imiquimod in high-grade cervical intraepithelial neoplasia: A systematic review and meta-analysis.

OBJECTIVE: A major side effect of cervical excision for high-grade cervical intraepithelial neoplasia (CIN) is premature birth. A non-invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high-grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared with surgical treatment and placebo. METHODS: Databases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr-HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist. RESULTS: Five studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod-treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03-8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59-33.27) for histological regression to ≤CIN 1. The hr-HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62-23.77). CONCLUSIONS: The histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.

Influence of sequential HTC pre-treatment and pyrolysis on wet food-industry wastes: Optimisation toward nitrogen-rich hierarchical carbonaceous materials intended for use in energy storage solutions.

Due to elevated protein content, the food-industry bio-wastes are promising feedstock to produce hierarchical (micro-mesoporous) carbonaceous materials with the intended use as electrodes in the energy storage solutions. However, the high initial water content, makes their direct activation through high-temperature processes costineffective due to significant heat requirements. In this study, the influence of pretreatment with hydrothermal carbonization (HTC) on wet food-industry bio-wastes, further pyrolysed, was investigated. Selected wastes (brewer's spent grains, spent coffee grains and spent sugar beets) were pre-treated by HTC at 180 °C or 240 °C, and then pyrolysed at 500 °C or 700 °C. Obtained materials were examined using elemental analysis, gas adsorption (N2 and CO2) and FT-IR. Besides minor differences caused by the bio-composition of wastes, the general trends were similar for feedstock. The pre-treatment had a beneficial influence on the properties of all wastes. The HTC at 180 °C and pyrolysis at 700 °C for all wastes show the most promising total specific surface area 560 ± 10 m2/g and accessible specific surface area 96 m2/g. Those conditions simultaneously did not reduce the total solid yield in comparison to the one-step process. The pre-treatment at 240 °C led to elevated nitrogen incorporation in the carbonaceous structure compared to HTC at 180 °C. However, it formed a hierarchical structure that was not stable for the thermal treatment. Study proves the HTC pre-treatment at 180 °C is beneficial for the conversion of food-industry bio-wastes into hierarchical carbonaceous material for their use in the energy storage systems application.

Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients.

CD103-positive tissue resident memory-like CD8+ T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future.

Valorization of the poultry litter through wet torrefaction and different activation treatments.

The increase in volume in bio-waste is inseparable from the production of biomass derived commodities. To reduce the use of conventional resources, the valorization of waste streams is gaining importance, and the valorisation of poultry litter fits perfectly into such scheme. This study shows a possible valorization of wet torrefied (300 °C) poultry litter (WTPL) through activation and its further use as a fertilizer, and as a wastewater micro-pollutant absorbent. The WTPL was activated thermally, physically (CO2) and chemically (KOH) at two different temperatures (600 °C and 800 °C) and 30 min residence time. The properties of ACs were evaluated based on results of the elemental and proximate analysis, suspension pH measurement, ICP-OES, FT-IR, N2 and CO2 adsorption and quantity of absorbed methylene blue (MB). The yields in thermal and physical ACs were comparable, but much higher than ACs from chemical activation (c.a. 50% and 15% at 600 °C and c.a. 47% and 6.5% at 800 °C). The thermal and physical ACs showed good suitability for application as a fertilizer due to their high macro- and micro-nutrients and low heavy metals concentration. Carbons activated with KOH proved their usefulness as wastewater pollutant absorbers through high MB's absorption (675.8 mg/g for 600 °C and 872.8 mg/g for 800 °C). Results state that the valorization of PL through activation is possible, and the selection of the activation method affects the final application of obtained material.

[Dignity, freedom, embodiment : Ethical categories concerning the use of freedom-depriving measures in people with dementia in acute care settings]. / Würde, Freiheit, Leiblichkeit : Ethische Kategorien bei der Anwendung freiheitsentziehender Maßnahmen bei Menschen mit Demenz im Akutkrankenhaus.

The use of freedom-depriving measures (physical and medicinal restraints) in people with cognitive impairment or dementia in clinical care settings is of ongoing importance. At the same time, these coercive measures are not only heavily debated but also in most cases ethically questionable from the perspective of the ethics of human dignity. Usually, the ethical evaluation of freedom-depriving measures follows classical paradigms of medical ethics, such as the Principles of Biomedical Ethics by Beauchamp and Childress. To enrich the debate at this point, the ethical category of embodiment ("Leiblichkeit" ) is introduced and discussed after a short summary of the ethical problem at hand. The phenomenon of the living body that has received increasingly more attention in several sciences since the proclaimed "corporeal turn" enables new perspectives towards human dignity, freedom and deprivation of freedom: freedom-depriving measures do not take place in an invisible realm of ideas but are directly applied to the psychophysical unity that is the living body of a person. Thus, freedom-depriving measures are an intervention into the bodily autonomy of the human being and the personal freedom that is manifested in the living body. The concept of the living body ("Leib") that is applied here, signifies more than just a physical object and is especially apt to capture the (inter)subjective dimension that has to be taken into account here. Finally, it will have to be investigated whether the use of medicinal restraints represents an especially serious interference into the sphere of human embodiment. Once introduced into the debate on freedom-depriving measures in clinical care, the category of embodiment can warrant decisive new emphases.

Effect of protein during hydrothermal carbonization of brewer's spent grain.

This study has two targets: Studying the extraction of the initial protein content from brewer's spent grain and the impact of protein's extraction on the chemical-physical properties of produced hydrochars. The protein was extracted from brewer's spent grains using the pH-shifting method. The extracted protein was quantified and characterized by their amino acid profile. The hydrothermal treatment was applied at 190 °C and 220 °C for 0.5 h, 1 h, 2 h, and 4 h. The hydrochars and process water were collected and assayed. The hydrochar after protein extraction reveals the lowest yield to hydrochars (67.10-45.14%), higher C/N ratio (19.66-21.33) and lower ash content (1.52-1.72 wt%) compared to the hydrochar without extraction.

Outcome of surgery in advanced ovarian cancer varies between geographical regions; opportunities for improvement in The Netherlands.

INTRODUCTION: The care for patients with epithelial ovarian cancer(EOC) is organised in eight different geographical regions in the Netherlands. This situation allows us to study differences in practice patterns and outcomes between geographical regions for patients with FIGO stage IIIC and IV. METHODS: We identified all EOC patients who were diagnosed with FIGO stage IIIC or IV between 01.01.2008 and 31.12.2015 from the Netherlands Cancer Registry. Descriptive statistics were used to summarize treatment and treatment sequence(primary cytoreductive surgery(PCS) or neoadjuvant chemotherapy and interval cytoreductive surgery(NACT-ICS)). Moreover, outcome of surgery was compared between geographical regions. Multilevel logistic regression was used to assess whether existing variation is explained by geographical region and case-mix factors. RESULTS: Overall, 6,741 patients were diagnosed with FIGO IIIC or IV disease. There were no differences in the percentage of patients that received any form of treatment between the geographical regions(range 80-86%, P = 0.162). In patients that received cytoreductive surgery and chemotherapy, a significant variation between the geographical regions was observed in the use of PCS and NACT-ICS(PCS: 24-48%, P < 0.001). The percentage of complete cytoreductive surgeries after PCS ranged from 10 to 59%(P < 0.001) and after NACT-ICS from 37 to 70%(P < 0.001). Moreover, geographical region was independently associated with the outcome of surgery, also when adjusted for treatment sequence(P < 0.001). CONCLUSION: We observed a significant variation in treatment approach for advanced EOC between geographical regions in the Netherlands. Furthermore, the probability to achieve no residual disease differed significantly between regions, regardless of treatment sequence. This may suggest that surgical outcomes can be improved across geographical regions.

Novel approach of phosphate-reclamation as struvite from sewage sludge by utilising hydrothermal carbonization.

Hydrothermal carbonization (HTC) showed promising performance as an alternative sewage sludge treatment already, as the draining ability of sludge is improved while fuel properties of the yielded hydrochar are superior to native sludge. On the other hand, the sole combustion of sewage sludge and its corresponding hydrochars are a waste in terms of nutrients like phosphorus and nitrogen. Therefore, a combination of HTC and a nutrient recycling strategy via the precipitation of phosphate and nitrogen as struvite (magnesium ammonium phosphate) are introduced in this research. We used an anaerobically digested sewage sludge with high loads of aluminium- and ironsalts. Phosphate release cannot be reached by HTC alone, as phosphate is heavily bound in stable iron- and aluminium-associations. An acid leaching step removes it from the hydrochar (58.5-94.8% P), while the process liquid arising from HTC is used as ammonium source (107-291 mmol l-1NH4). After adjusting pH and addition of a magnesium source, struvite is rapidly precipitated in high purity. Nitric acid is used as a "catalyst" in HTC to improve the degree of carbonization on one hand but also improve the phosphate recovery on the other hand by increasing the amount of ammonium available for struvite formation in the process liquid. The highest total recovery rate of phosphate from sludge was 82.5 wt.% and therefore this approach showed to be a serious alternative to other P-recovery techniques.

[Hot rods in the ICU : What is the antibiotic mileage of your renal replacement therapy?] / Boliden auf der Intensivstation : Wie viel Antibiotika verbraucht Ihre Nierenersatztherapie pro Tag?

We would neither be disappointed nor upset if the gas mileage on the sticker of a car didn't match our personal, real-life fuel consumption. Depending on our daily route to work, our style of accelerating and the number of passengers in our carpool, the gas mileage will vary. As soon as the falcon wing door of our car is closed and entrance to the ICU is granted, we tend to forget all of this, even though another hot rod is waiting there for us. Renal replacement therapy is like a car; it fulfills goals, such as the removal of uremic toxins and accumulated fluids, but it also "consumes" (removes) antibiotics. Unlike catecholamines, where we have the mean arterial pressure on our ICU dashboard, we do not have a gauge to measure antibiotic "consumption", i.e. elimination by renal replacement therapy. This manuscript describes the principles and basic knowledge to improve dosing of antibiotics in critically ill patients undergoing renal replacement therapy. As in modern cars, we briefly touch on hybrid therapies combining renal replacement therapy with extracorporeal lung support or adsorbent technologies that remove cytokines or bacteria. Further, the importance of considering body size and body composition is addressed, especially for choosing the right initial dose of antibiotics. Lastly we point out the dire need to increase the availability of timely and affordable therapeutic drug monitoring on the most commonly used antiinfectives, ideally using point-of-care devices at the bedside.

TOPical Imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia (TOPIC-2 trial): a study protocol for a randomized controlled trial.

BACKGROUND: Cervical dysplasia (cervical intraepithelial neoplasia (CIN)) is caused by Human Papillomavirus (HPV) and is most common in women of reproductive age. Current treatment of moderate to severe CIN is surgical. This procedure has potential complications, such as haemorrhage, infection and preterm birth in subsequent pregnancies. Moreover, 15% of women treated for high grade CIN develop residual/recurrent CIN or cervical cancer after surgical excision. Finally, 75-100% of patients with a residual and recurrent CIN 2-3 lesion are still HPV positive. They could possibly benefit from an alternative medical treatment, which aims to eliminate HPV. The primary study objective is to evaluate the effectivity of imiquimod 5% cream compared to treatment with Large Loop Excision of the Transformation Zone (LLETZ) for recurrent/residual CIN. METHODS/DESIGN: This study is a multicentre, non-inferiority randomized single blinded study. The study population consists of female patients with histological proven residual/recurrent CIN after previous surgical treatment. Four hundred thirty-three patients will be included in the Netherlands. The first 35 patients will be included in a pilot study to prove non-futility. Included patients will be randomized to receive either 5% imiquimod cream or LLETZ treatment. Imiquimod will be inserted three times a week intravaginally for a period of 16 weeks using a vaginal applicator. Ten weeks after the end of imiquimod treatment a biopsy will be taken for treatment response. In case of progressive or stable disease a LLETZ will be performed. At 12 and 24 months after the start of treatment cytology will be taken for follow up. The LLETZ group will be treated according to the current guidelines. Throughout the study, HPV typing and quality of life will be tested. DISCUSSION: Repeated LLETZ in women with residual/recurrent CIN lesions has complications. We would like to possibly offer alternative treatment in a selected group to avoid these risks. Moreover, we monitor treatment efficacy, side effects and long-term recurrence rates. TRIAL REGISTRATION: Medical Ethical Committee approval number: NL 53792.078.15. Affiliation: Erasmus Medical Center. Registration number ClinicalTrials.gov : NCT02669459 , date of registration: 27th January 2016.

Dietary approaches reducing boar taint-Importance of Lawsonia intracellularis colonisation for interpreting results.

In the fattening of male pigs, boar odour is a major problem with regard to the acceptance of the meat by consumers. Skatole can be one cause. Tryptophan from non-digested feed ingredients and intestinal cell debris can be the precursor in skatole formation. Lawsonia intracellularis, one of the most widespread pathogens in swine, promotes the epithelial cell turnover and might favour the tryptophan influx into the hindgut. Therefore, the question arises how far the severity of a Lawsonia intracellularis infection has an effect on results of dietary experiments with specific issues. Fifty finishing boars from a specific pathogen-free farm were randomly allotted to ten boxes in five feeding groups. Natural developing Lawsonia intracellularis colonisation was monitored serologically (twice individually) and molecular biologically (weekly individually). Over 4 weeks, animals were fed either a finely ground pelleted diet (FP), a coarsely ground meal diet (CM), a meal diet either with 22% cracked corn (CORN), 16.9% dried whey (WHEY) or 30% raw potato starch (RPS). Fifty % of animals showing lower differences in serological Lawsonia intracellularis values between the start and the end of the trial were characterised by a higher dry matter content in faeces (256 ± 29.4 vs. 239 ± 23.6 g/kg). Lawsonia intracellularis-negative caecal samples showed the highest butyrate concentrations (27.2 ± 7.53 mmol/kg). Lawsonia intracellularis-negative faecal samples of group FP showed the highest DM levels in faeces (neg: 290 ± 46.1/pos: 250 ± 52.2 g/kg); negative samples from group RPS had the lowest values (217 ± 24.4 g/kg). Lawsonia intracellularis-negative faecal samples from the group CM were lower in skatole than positive samples (82.8 ± 32.8 vs. 119 ± 29.3 µg/g DM). RPS group samples without pathogen detection had the lowest skatole concentrations (30.5 ± 36.3 µg/g DM). This study provides first evidence that clinically unremarkable colonisation with intestinal pathogens might influence the results of dietary approaches.

Elimination of micropollutants by activated carbon produced from fibers taken from wastewater screenings using hydrothermal carbonization.

Activated Carbon (AC) can be used to reduce organic micropollutants (OMPs) in wastewater treatment plants (WWTPs). While producing ACs conventionally still damages the environment, this can be reduced by using renewable raw material from waste streams und producing AC locally. In this study, fibers (toilet paper) were separated out of wastewater by screening WWTP influents in full scale and then used as a no-cost, carbon-rich and heavy metal-poor raw material to produce ACs. Pretreatment was hydrothermal carbonization (HTC). Thereafter, they were activated using KOH to generate activated carbons (HTC-ACs). Their functional groups were characterized using FT-IR, and the alteration of their chemical composition was traced by elementary analysis. Adsorption tests were performed with nitrogen (BET surface) and methylene blue as standard tests. The adsorption capacity was tested with WWTP effluent and the removal of UVA254 as a surrogate for OMP removal was measured. After HTC and activation 13-16% of the fibers dry mass was obtained as HTC-ACs. Higher dehydration and formation of aromatic structures on the HTC-ACs were detected with FT-IR as HTC and activation temperature increased. BET surface and methylene blue adsorption of some HTC-ACs was higher than the Reference AC. Nevertheless, their ability to reduce OMPs is still lower than the Reference AC due to the different nature of their functional groups and their microporous structure that is not fully accessible for OMPs in real wastewater. Further research has to be carried out to adjust the production process so as to obtain mesoporous HTC-ACs tailored to reduce OMP concentrations and to close the carbon loop within WWTPs.

Review of transmission routes of 24 infectious diseases preventable by biosecurity measures and comparison of the implementation of these measures in pig herds in six European countries.

This study aimed to review the transmission routes of important infectious pig diseases and to translate these into biosecurity measures preventing or reducing the transmission between and within pig herds. Furthermore, it aimed to identify the level of implementation of these measures in different European countries and discuss the observed variations to identify potentials for improvement. First, a literature review was performed to show which direct and indirect transmission routes of 24 infectious pig diseases can be prevented through different biosecurity measures. Second, a quantitative analysis was performed using the Biocheck.UGent™, a risk-based scoring system to evaluate biosecurity in pig herds, to obtain an insight into the implementation of these biosecurity measures. The database contained farm-specific biosecurity data from 574 pig farms in Belgium, Denmark, France, Germany, the Netherlands and Sweden, entered between January 2014 and January 2016. Third, a qualitative analysis based on a review of literature and other relevant information resources was performed for every subcategory of internal and external biosecurity in the Biocheck.UGent™ questionnaire. The quantitative analysis indicated that at the level of internal, external and overall biosecurity, Denmark had a significantly distinct profile with higher external biosecurity scores and less variation than the rest of the countries. This is likely due to a widely used specific pathogen-free (SPF) system with extensive focus on biosecurity since 1971 in Denmark. However, the observed pattern may also be attributed to differences in data collection methods. The qualitative analysis identified differences in applied policies, legislation, disease status, pig farm density, farming culture and habits between countries that can be used for shaping country-specific biosecurity advice to attain improved prevention and control of important pig diseases in European pig farms.

Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial.

The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

[Technique-based game for daycare visitors with and without dementia : Effects, heuristics and correlates]. / Technikbasiertes Spiel von Tagespflegebesuchern mit und ohne Demenz : Effekte, Heuristiken und Korrelate.

BACKGROUND: Playing of old people with or without dementia have not yet been substantially investigated. OBJECTIVE: This study deals with the acceptance and impact of a tablet-based memory game, which was played on a weekly or semiweekly basis by visitors in two daycare units. MATERIAL AND METHODS: Within the framework of focus groups the technical system was adapted for elderly users. The video-assisted data at the level of the game and the dynamics were investigated with respect to interaction and communication. RESULTS: The analysis of psychological observation forms and game protocols, which were conducted over a period of 3 months, indicated different effects of the game on psychosocial and cognitive activation. The individual memory cards in particular served as an intensification of communication and a stimulation of episodic memory. Finally, with video analysis during the whole game setting three theoretical relationship patterns of the spheres playing and speech could be depicted. CONCLUSION: Coherence, separation and incoherence of playing and speech are different forms of interaction in which individual and collaborative competences of people with and without dementia can be visualized. Furthermore, the study provides evidence for the cultural theory of playing by Huizinga.

TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): study protocol for a randomized controlled trial.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the premalignant condition of cervical cancer. Whereas not all high grade CIN lesions progress to cervical cancer, the natural history and risk of progression of individual lesions remain unpredictable. Therefore, high-grade CIN is currently treated by surgical excision: large loop excision of the transformation zone (LLETZ). This procedure has potential complications, such as acute haemorrhage, prolonged bleeding, infection and preterm birth in subsequent pregnancies. These complications could be prevented by development of a non-invasive treatment modality, such as topical imiquimod treatment. The primary study objective is to investigate the efficacy of topical imiquimod 5% cream for the treatment of high-grade CIN and to develop a biomarker profile to predict clinical response to imiquimod treatment. Secondary study objectives are to assess treatment side-effects, disease recurrence and quality of life during and after different treatment modalities. METHODS/DESIGN: The study design is a randomized controlled trial. One hundred forty women with a histological diagnosis of high-grade CIN (CIN 2-3) will be randomized into two arms: imiquimod treatment during 16 weeks (experimental arm) or immediate LLETZ (standard care arm). Treatment efficacy will be evaluated by colposcopy with diagnostic biopsies at 20 weeks for the experimental arm. Successful imiquimod treatment is defined as regression to CIN 1 or less, successful LLETZ treatment is defined as PAP 1 after 6 months. Disease recurrence will be evaluated by cytology at 6, 12 and 24 months after treatment. Side-effects will be evaluated using a standardized report form. Quality of life will be evaluated using validated questionnaires at baseline, 20 weeks and 1 year after treatment. Biomarkers, reflecting both host and viral factors in the pathophysiology of CIN, will be tested at baseline with the aim of developing a predictive biomarker profile for the clinical response to imiquimod treatment. DISCUSSION: Treatment of high-grade CIN lesions with imiquimod in a selected patient population may diminish complications as a result of surgical intervention. More knowledge on treatment efficacy, side effects and long-term recurrence rates after treatment is necessary. TRIAL REGISTRATION: EU Clinical Trials Register EU-CTR2013-001260-34 . Registered 18 March 2013. Medical Ethical Committee approval number: NL44336.068.13 (Medical Ethical Committee Maastricht University Hospital, University of Maastricht). Affiliation: Maastricht University Hospital. Registration number ClinicalTrials.gov: NCT02329171.

Consecutive magnetic resonance imaging during brachytherapy for cervical carcinoma: predictive value of volume measurements with respect to persistent disease and prognosis.

BACKGROUND: Cervical cancer is associated with a high yearly mortality. The presence of persistent disease after radiotherapy is a significant predictor of patient survival. The aim of our study was to assess if tumor volume regression measured with MR imaging at the time of brachytherapy can discriminate between patients who eventually will achieve a complete response to radiotherapy from those who will not. The second objective was to evaluate whether tumor volume regression predicts overall treatment failure. METHODS: MRI was evaluated quantitatively in 35 patients; by means of tumor volumetry on T2-weighted MR images before treatment, at the first BCT application, and at the final BCT. The MR images were independently analyzed by two investigators. As a reference standard histopathologic confirmation of residual tumor and/or clinical exam during follow-up > 1 year were used. Area under the curve were compared, P-values <0.05 were considered significant. RESULTS: There was a good correlation between volume measurements made by the two observers. A residual tumor volume >9.4 cm(3) at final BCT and tumor volume regression < 77 % of the pre-treatment volume were significantly associated with local residual tumor after completion of therapy (p < 0.02) (AUC, 0.98-1.00). A volume >2.8 cm(3) at final BCT was associated with overall treatment failure (p < 0.03). CONCLUSION: Our study shows that volume analysis during BCT is a predictive tool for local tumor response and overall treatment outcome. The potential of local response assessment to identify patients at high risk of overall treatment failure is promising.

Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients.