Use of Sensor Array Analysis to Detect Ovarian Cancer through Breath, Urine, and Blood: A Case-Control Study.

Ovarian cancer (OC) is the eighth most common cancer in women. Since screening programs do not exist, it is often diagnosed in advanced stages. Today, the detection of OC is based on clinical examination, transvaginal ultrasound (US), and serum biomarker (Carbohydrate Antigen 125 (CA 125) and Human Epididymis Protein 4 (HE4)) dosage, with a sensitivity of 88% and 95%, respectively, and a specificity of 84% for US and 76% for biomarkers. These methods are clearly not enough, and OC in its early stages is often missed. Many scientists have recently focused their attention on volatile organic compounds (VOCs). These are gaseous molecules, found in the breath, that could provide interesting information on several diseases, including solid tumors. To detect VOCs, an electronic nose was invented by a group of researchers. A similar device, the e-tongue, was later created to detect specific molecules in liquids. For the first time in the literature, we investigated the potential use of the electronic nose and the electronic tongue to detect ovarian cancer not just from breath but also from urine, blood, and plasma samples.

An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked recessive lysosomal storage disorder due to a mutation in the lysosomal enzyme iduronate-2-sulfatase (IDS) gene. IDS deficiency leads to a progressive, multisystem accumulation of glycosaminoglycans (GAGs) and results in central nervous system (CNS) manifestations in the severe form. We developed up to clinical readiness a new hematopoietic stem cell (HSC) gene therapy approach for MPS II that benefits from a novel highly effective transduction protocol. We first provided proof of concept of efficacy of our approach aimed at enhanced IDS enzyme delivery to the CNS in a murine study of immediate translational value, employing a lentiviral vector (LV) encoding a codon-optimized human IDS cDNA. Then the therapeutic LV was tested for its ability to efficiently and safely transduce bona fide human HSCs in clinically relevant conditions according to a standard vs. a novel protocol that demonstrated superior ability to transduce bona fide long-term repopulating HSCs. Overall, these results provide strong proof of concept for the clinical translation of this approach for the treatment of Hunter syndrome.

Modeling the space-time correlation of pulsed twin beams.

Entangled twin-beams generated by parametric down-conversion are among the favorite sources for imaging-oriented applications, due their multimodal nature in space and time. However, a satisfactory theoretical description is still lacking. In this work we propose a semi-analytic model which aims to bridge the gap between time-consuming numerical simulations and the unrealistic plane-wave pump theory. The model is used to study the quantum correlation and the coherence in the angle-frequency domain of the parametric emission, and demonstrates a [Formula: see text] growth of their size as the gain g increases, with a corresponding contraction of the space-time distribution. These predictions are systematically compared with the results of stochastic numerical simulations, performed in the Wigner representation, of the full model equations: an excellent agreement is shown even for parameters well outside the expected limit of validity of the model.

Tailoring parametrectomy for early cervical cancer (Stage IA-IIA FIGO): a review on surgical, oncologic outcome and sexual function.

INTRODUCTION: Cervical cancer is currently one of the most common cancers afflicting the female population worldwide and in industrialized countries the presence of screening and a specific diagnostic and therapeutic process has favored early diagnosis of cervical cancer. In literature have found that reducing the radicality on the parametria in early cervical cancer (ECC), reduces complications without impacting oncological outcomes, but the data in the literature are not yet clear. EVIDENCE ACQUISITION: Searching on PubMed, we included 1473 articles from January 1974 to 2020. We identified all the studies that compared different type of radical hysterectomy in the primary surgical treatment of ECC. 16 articles were elected for the review. EVIDENCE SYNTHESIS: Modified radical hysterectomy (Piver II/Querleu-Morrow Type B) in ECC, if compared to CRH (Piver III/Querleu-Morrow Type C2), is not associated with worse cancer outcome and patient survival, but it is associated with a minor operating time, lower blood loss and minor bladder dysfunction. Nerve sparing radical hysterectomy approach (NSRH/Querleu-Morrow Type C1) compared to CRH (Piver III/Type C2) in the ECC, with our data we can confirm a non-inferiority regarding the oncological outcome. CONCLUSIONS: Reduced radicality on the parametrium offers positive effects on the quality of life (sexual life and bladder function) of patients without impacting on survival, oncological outcome.

Hot-spots and gain enhancement in a doubly pumped parametric down-conversion process.

We experimentally investigate the parametric down-conversion process in a nonlinear bulk crystal, driven by two non-collinear pump modes. The experiment shows the emergence of bright hot-spots in modes shared by the two pumps, similar to the phenomenology recently observed in 2D nonlinear photonic crystals. By exploiting the spatial walk-off between the two extraordinary pump modes, we have been able to recreate a peculiar resonance condition, reported by a local enhancement of the parametric gain, which corresponds to a transition from a three-mode to a four-mode coupling. From a quantum point of view, this opens the way to the generation of multimode entangled states of light, such as tripartite or quadripartite states, in simple bulk nonlinear sources.

Examining policy cohesion for cervical cancer worldwide: analysis of WHO country reports.

INTRODUCTION: Cervical cancer is controllable through appropriate interventions such as vaccination, screening, treatment, early diagnosis and palliative care. The greatest burden of cervical cancer lies in low-income countries (LIC) where most of these services are missing or developed asymmetrically. Indeed, it is important to have not just an expansion, but a symmetric and concordant development of each service. Therefore, policies of countries should be aligned to provide concordant services and achieve the best outcomes with available resources. This is called 'policy cohesion' and for the first time in literature we will analyse cervical cancer policy coherence in all the 194 WHO member states. METHODS: The study is based on the 2017 WHO Non-Communicable Disease Country Capacity Surveys (NCD CCS). Although the survey covers multiple non-communicable diseases, in this report we will only discuss those results pertaining to cervical cancer, analysing the cervical cancer policy cohesion of 194 WHO member states, divided by WHO region and World Bank income group. RESULTS: Human papilloma virus vaccination exists in 53% of countries. 76% of countries offer cervical screening: among these countries, treatment, early diagnosis guidelines and palliative care are missing in 13%, 13% and 40%, respectively. In the African region, this discord is even more profound: 32%, 17% and 60%, respectively. CONCLUSION: Especially in those settings where resources are limited, early detection guidelines, treatment and palliative care should be implemented along with secondary prevention strategies. Symmetric development of concordant cervical cancer services maximises cervical cancer control efficacy.

Sentinel lymph node in cervical cancer: a literature review on the use of conservative surgery techniques.

INTRODUCTION: Sentinel lymph node detection is a surgical procedure that allow to avoid systematic lymphadenectomy in those tumors in early stage where lymph node spread is not sure. If the sentinel lymph node is not involved by tumor in 98-99% of case other lymph nodes are clean. The reason why less radical surgery is chosen is linked to the lower postoperative morbidity rate, the risk of lower limb lymphedema decreases. The aim of this review was to summarize what is the state of art of using the sentinel lymph node dissection (SLD) technique and what are the future goals to improve the safety and the reliability. EVIDENCE ACQUISITION: We have conducted a review of the literature of the past 10 years to understand the attitudes of oncologist gynecologists in the world to the conservative treatment of cervical cancer. We only selected articles from 2010 onwards, which meet the inclusion criteria. EVIDENCE SYNTHESIS: The detection rate varies from 83% to 100%. The bilateral detection rate, on the other hand, varies from 42% to 100%. The false negative rate ranges from 4% to 12%. Sensitivity varies from 20.7% (considering the frozen section) to 100%. CONCLUSIONS: Indocyanine green is the most reliable and performing tracer for the search of the sentinel lymph node; that the false intraoperative negative rate is too high to be sure not to subject the patient to an incorrect therapeutic procedure; data concerning the safety and survival of conservative lymphadenectomy (SLND) compared to systematic lymphadenectomy are still lacking in the literature and therefore we are awaiting the results of the two ongoing randomized clinical trials that will allow us to have more significant scientific data.

How to reduce the impact of cervical cancer worldwide: Gaps and priority areas identified through the essential cancer and primary care packages: An analysis of effective interventions.

BACKGROUND: Cervical cancer is a preventable cancer; therefore, countries should provide strategic, evidence-based health services to reduce its incidence and impact on their populations. Two packages of health services that group together all the services related to cervical cancer, the Essential Cancer Package (9 interventions) and the Primary Care Package (5 interventions), are defined in this article with the aim of assessing the global status of the availability of health services and their coverage in 194 countries worldwide. METHODS: The study was based on the 2017 World Health Organization (WHO) Noncommunicable Disease Country Capacity Survey. Although the survey covered multiple noncommunicable diseases, this report examined only those results pertaining to cervical cancer in the 194 WHO member states divided by WHO region and World Bank income. RESULTS: Only 21% of the countries reported providing all 9 interventions of the Essential Cancer Package, with the highest proportions being found in Europe (45.3%) and among high-income countries (HICs; 54.3%). As for the Primary Care Package, only 19.1% of countries provided all 5 interventions, with the highest proportions being found in Europe (39.6%) and among HICs (45.5%). CONCLUSIONS: The complete development and appropriate coverage of each service listed in both the Essential Cancer Package and the Primary Care Package are essential to reduce the impact of cervical cancer worldwide, and they should be integrated into all cancer control planning efforts.

Effectiveness of CO2 laser on urogenital syndrome in women with a previous gynecological neoplasia: a multicentric study.

BACKGROUND: Many women diagnosed with gynecological cancers undergo adjuvant therapy, which may lead to transient or permanent menopause that ultimately leads to urogenital syndrome and vulvovaginal atrophy. Studies advise against the use of estrogen in women with a history of hormone-dependent cancer. One alternative is vaginal microablative fractional CO2 laser, which promotes tissue regeneration through the production of collagen and elastic fibers. OBJECTIVE: To evaluate the effectiveness of CO2 laser in the treatment of urogenital syndrome-in particular, symptomatic vulvovaginal atrophy in women who have survived gynecological cancers. METHODS: A retrospective study was carried out, including all patients with a history of gynecological cancers and vulvovaginal atrophy who underwent CO2 laser treatment between November 2012 and February 2018 in four Italian centers. The study was approved by the local ethics committee of each participating institution. The inclusion criteria were women aged between 18 and 75; Eastern Cooperative Oncology Group performance status <2; and history of breast, ovarian, cervical, or uterus cancer. Patients had to have vulvovaginal atrophy and at least one of the following symptoms of urogenital syndrome: vaginal dryness, dyspareunia, vaginal introitus pain, burning, or itching. Three applications were administered at baseline, 30 days, and 60 days. All patients were evaluated before the first laser session, at each session, and 4 weeks after the last session. In particular, patients were asked to indicate the intensity of symptoms before the first session and 4 weeks after the last session, using Visual Analog Scale (VAS) scoring from 0 ('no discomfort') to 10 ('maximum discomfort'). RESULTS: A total of 1213 patients underwent CO2 laser treatment and of these, 1048 were excluded because they did not meet the inclusion criteria in the analysis. Finally, a total of 165 patients were included in the study. The mean age at the time of treatment was 53 years (range 31-73). Dryness improved by 66%, dyspareunia improved by 59%, burning improved by 66%, pain at introitus improved by 54%, and itching improved by 54%. The side effects were evaluated as pain greater than VAS score 6 during and after the treatment period. No side effects were seen in any sessions. CONCLUSIONS: Fractional microablative CO2 laser therapy offers an effective strategy in the management of the symptoms of genitourinary syndrome in post-menopausal women and in survivors of gynecological cancer.

Ovarian cancer relapse: From the latest scientific evidence to the best practice.

Ovarian cancer (OC) is the fifth most common cause of cancer death in women worldwide. Despite treatment options have continued to improve in recent years, the recurrence rate is still high; in fact around 80% of patients relapses within 18 months. Recently, the scientific landscape is agree in asserting that the ovarian cancer is not a single disease but the outcome of patients depends from the molecular and biological characterization of tumor tissue. In this scenario, molecular targeted therapy given alone or in combination with chemotherapy is showing significant results. We review the different options for the treatment of ovarian cancer recurrence, including the role of surgery, in order to try outlining a possible treatment algorithm evaluating the recent scientific literature and the most important trials.

The role of human epididymis protein 4 as a biomarker in gynecologic malignancies.

INTRODUCTION: The serum levels of glycoprotein human epididymis protein 4 (HE4) have been widely investigated in patients with ovarian cancer as a tumor marker to differentiate benign gynecological tumors from ovarian cancers (OC). A few studies demonstrated the promising role of HE4 in endometrial cancer (EC) too. The aim of this review is to provide an outline of published studies investigating HE4 in the diagnosis of gynecologic malignancies, focusing on its role in OC and EC. EVIDENCE ACQUISITION: We conducted a systematic review of literature from January 1952 to June 2018 on the role of HE4 in OC and EC focusing on the diagnostic power in terms of sensitivity and specificity. EVIDENCE SYNTHESIS: We identified 49 articles with an overall sample size of 12,631 patients in OC group and five studies with an overall sample size of 1221 patients in EC group. We stated that HE4 had a pooled sensitivity of 78% and specificity of 86% in the detection of borderline or malignant OC and a pooled sensitivity of 78.8% and specificity of 100% in EC diagnosis. CONCLUSIONS: This systematic review confirms the importance of HE4 in the diagnosis of epithelial ovarian cancer and its promising role in endometrial cancer (endometrioid histology).

Golden Ratio Gain Enhancement in Coherently Coupled Parametric Processes.

Nonlinear optical processes are an essential tool in modern optics, with a broad spectrum of applications, including signal processing, frequency conversion, spectroscopy and quantum optics. Ordinary parametric devices nevertheless still suffer from relatively low gains and wide spectral emission. Here we demonstrate a unique configuration for phase-matching multiple nonlinear processes in a monolithic 2D nonlinear photonic crystal, resulting in the coherent parametric emission of four signal and idler modes, featuring an exponential gain enhancement equal to the Golden Ratio. The results indicate a new route towards compact high-brightness and coherent sources for multi-photon generation, manipulation and entanglement, overcoming limitations of conventional parametric devices.

The role of macroplastique implantation in the management of occult urinary stress incontinence.

OBJECTIVE: Pelvic floor disorders, in particular pelvic organ prolapse (POP) and stress urinary incontinence (SUI), are common in women. There is a described higher risk to develop postoperative SUI also in preoperatively continent women: this happens because in 30% of women the relief of the urethral obstruction caused by prolapse, unmasks a pre-existing compromised urethral function and thus an "occult" or potential SUI. The aims of this study were to evaluate the role of Macroplastique® implant, TVT-O or surgery alone in the management of occult urinary stress incontinence during prolapse surgery in terms of success rate and adverse events. STUDY DESIGN: We enrolled 47 consecutive patients scheduled to vaginal prolapse surgery who did not report symptoms of stress incontinence. We collected surgical data, success and complication rates. Moreover we compared all the data with retrospective ones regarding surgery plus concomitant TVT-O (39 pts) and surgery alone (41 pts). RESULTS: At 12-months follow-up, we reported a success rate of 87,2% in the "macroplastique group", comparable to the "surgery plus TVT-O group", with a statistically significant difference in comparison to the "surgery alone" group. "Surgery + TVT-O" group reported a higher rate of major complications (p<0,01) in comparison to the other groups. CONCLUSIONS: Postoperative SUI prevention at the time of prolapse repair remains a challenging issue. In selected patients, Macroplastique may play an interesting role having a good success rate and a low complication rate and for these reasons it may be proposed as A concomitant procedure during POP surgery.

Hormone replacement therapy in cancer survivors: Utopia?

As growing of old women population, menopausal women will also increase: an accurate estimation of postmenopausal population is an essential information for health care providers considering that with aging, the incidence of all cancers is expected to increase. Hormone replacement therapy (HRT) has proven to be highly effective in alleviating menopausal symptoms such as hot flashes, night sweats, dyspareunia, sexual disorders, and insomnia and in preventing osteoporosis. According to preclinical data, estrogen and progesterone are supposed to be involved in the induction and progression of breast and endometrial cancers. Similarly, in epithelial ovarian cancer (EOC), the pathogenesis seems to be at least partly hormonally influenced. Is HRT in gynecological cancer survivors possible? The literature data are controversial. Many clinicians remain reluctant to prescribe HRT for these patients due to the fear of relapse and the risk to develop coronary heart disease or breast cancer. Before the decision to use HRT an accurate counselling should be mandatory in order to individualizing on the basis of potential risks and benefits, including a close follow-up. Nevertheless, we do believe that with strong informed consent doctors may individually consider to prescribe some course of HRT in order to minimize menopausal symptoms and disease related to hormonal reduction.

Long-term follow-up of bulking agents for stress urinary incontinence in older patients.

OBJECTIVE: Implantation of bulking agents represents a noninvasive procedure for the treatment of stress urinary incontinence (SUI) in all patients where a more invasive procedure may increase perioperative risks. The primary aim of this retrospective study was to evaluate the efficacy over time of bulking agent implantation. As secondary aims, we evaluated long-term (patients' subjective) satisfaction rate, rate of de novo urinary symptoms, and the impact of urinary incontinence on the quality of life. METHODS: All patients who underwent implantation of bulking agents between 1999 and 2013 at Campus Bio-Medico of Rome were retrospectively considered eligible for this study. Patients were interviewed using two standardized questionnaires: International Consultation on Incontinence Questionnaire Short Form and Patient Global Impression of Improvement. Cure rate, improvement rate, failure rate, and the onset of new symptoms were also investigated through specific questions. The original group of patients was then divided into two subgroups according to follow-up time (group A: shorter than median follow-up; group B: longer than median follow-up). RESULTS: Sixty-three patients were enrolled. Mean follow-up was 8.3 ±â€Š3.5 years with a range of 3.5 to 18 years. Fifteen (24%) cured patients (cure rate), 12 (19%) improved patients (improvement rate), 36 (57%) failed treatment (failure rate). We reported an overall success rate of 43%. No differences were reported among groups in terms of overall success rate (42% vs 44% for group A and group B, respectively). CONCLUSIONS: Bulking agent implantation is an effective treatment for people with intrinsic sphincter deficiency (type III SUI) and it is a valid alternative to more invasive surgeries in older patients. Moreover, it shows an overall success rate (43%) that remains high even after many years.

Anterior colporrhaphy plus inside-out tension-free vaginal tape for associated stress urinary incontinence and cystocele: 10-year follow up results.

AIMS: We report the success rate and complications rate of combined ultralateral anterior Colporrhaphy plus Tension-free Vaginal Tape (TVT-O) in a long-term (10 year) follow-up prospective survey. METHODS: Patients previously treated for associated stress urinary incontinence (SUI) and cystocele were subjected to annual follow-up for 10 year with a complete urogynecologic evaluation. Furthermore, an urodynamic assessment and a quality of life questionnaire (ICIQ-UI SF) were recorded at the 5th and 10th year of follow up. RESULTS: Fifty patients treated between June 2004 and May 2006 were included in the analysis. Five patients did not return to 5-yr follow-up: two patients developed a median tape erosion and three patients withdraw. At 10-yr follow-up two more patients withdraw for a total of seven patients lost to follow-up. After 10 years patients objectively cured from cystocele were 41 (95%) while patients objectively cured from SUI were 39 (91%). At 10th year follow-up 38 patients (89%) result cured from both SUI and cystocele, 3 (7%) patients result cured only from prolapse, 1 (2%) patient only from SUI, and 1 (2%) patient result objectively failed for both SUI and cystocele. The ICIQ-UI SF scores at 10th year follow-up was 6.2 ± 3.7. The late complication rate at 10th year follow-up was 32% (OAB symptoms 20%; Mixed incontinence 2%; Bladder outlet obstruction 0%; Dyspareunia 6%; Chronic pelvic pain 0%; Vaginal tape erosion 4%; Detrusor hyperactivity 0%). CONCLUSIONS: The combined procedures shown proved to be an effective and safe procedure to treat concomitant SUI and cystocele.

The Role of HE4, a Novel Biomarker, in Predicting Optimal Cytoreduction After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer.

OBJECTIVES: This study aimed to evaluate serum human epididymis protein 4 (HE4) changes during neoadjuvant chemotherapy (NACT) to establish HE4 predebulking surgery cutoff values and to demonstrate that CA125, HE4, and computed tomography (CT) taken together are better able to predict complete cytoreduction after NACT in advanced ovarian cancer patients. METHODS: From January 2006 to November 2015, patients affected by epithelial advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV), considered not optimally resectable, were included in this prospective study. After 3 cycles of NACT, all patients underwent debulking surgery and were allocated, according to residual tumor (RT), into group A (RT = 0) and group B (RT > 0). Serum CA125, HE4, and CT images were recorded during NACT and compared singularly and with each other in term of accuracy, sensitivity, specificity, and positive and negative predictive value. RESULTS: A total of 94 and 20 patients were included in group A and group B, respectively. The HE4 values recorded before debulking surgery correlated with RT. The identified HE4 cutoff value of 226 pmol/L after NACT was able to classify patients at high or low risk of suboptimal surgery, with a sensitivity of 75% and a specificity of 85% (positive predictive value, 0.87; negative predictive value, 0.70). The combination of CA125, HE4, and CT imaging resulted in the best combination with a sensitivity of 96% and a specificity of 92% (positive predictive value, 0.96; negative predictive value, 0.94). CONCLUSIONS: The novel biomarker HE4, in addition to CA125 and CT, is better able to predict the RT at debulking surgery and the prognosis of patients.

Lack of the QTc physiologic decrease during cardiac stress test in patients with type 2 diabetes treated with secretagogues.

Patients with type 2 diabetes are at increased susceptibility to a prolonged QT interval. Furthermore, insulin secretagogues, drugs used to treat diabetes, may prolong QT interval and provoke arrhythmias. We evaluated whether secretagogues can affect QTc interval during cardiac stress test in 20 patients with type 2 diabetes treated with secretagogues. ECG stress test was performed in all patients. QTc interval was calculated both before cardiac stress test (BCST) and at acme of cardiac stress test (ACST). Diabetic patients treated with secretagogues showed longer QTc-ACST values than those treated with metformin only. QTc-ACST values resulted shorter than QTc-BCST values in control group. Diabetic patients treated with secretagogues showed QTc-ACST values significantly longer than QTc-BCST values. In our study, diabetic patients treated with secretagogues did not show the QTc physiologic decrease that is a protective against arrhythmias. These results suggest to evaluate, in these patients, QT length, even during routine cardiac stress test.

Combination effect of fluoride dentifrices and varnish on deciduous enamel demineralization.

The aim of this study was to evaluate the anticaries potential of 500 or 1100 ppm F dentifrices combined with fluoride varnish using a pH-cycling regimen. Seventy primary canines were covered with nail polish, leaving a 4×4 mm window on their buccal surface, and randomly assigned into 7 groups (n = 10): S: sound enamel not submitted to the pH-cycling regimen or treatment; N: negative control, submitted to the pH-cycling regimen without any treatment; D1 and D2: subjected to the pH-cycling regimen and treated twice daily with 1100 or 500 ppm F dentifrice, respectively; VF: fluoride varnish (subjected to F-varnish before and in the middle of the pH-cycling regimen); and VF+D1 and VF+D2. After 10 days, the teeth were sectioned, and enamel demineralization was assessed by cross-sectional hardness at different distances from the dental surface. Data were analyzed using a two-way ANOVA followed by Tukey's test. Dentifrice with 1100 ppm F and the combination of F-varnish with the dentifrices significantly reduced enamel demineralization compared with the negative control (p < 0.05), but the isolated effects of F-varnish and dentifrice with low concentration were not significant (p > 0.05). The effect of combining F-varnish with the dentifrices was not greater than the effect of the dentifrices alone (p < 0.05). The data suggest that the combination of F-varnish with dentifrices containing 500 and 1100 ppm F is not more effective in reducing demineralization in primary teeth than the isolated effect of dentifrice containing 1100 ppm F.

Combination effect of fluoride dentifrices and varnish on deciduous enamel demineralization

The aim of this study was to evaluate the anticaries potential of 500 or 1100 ppm F dentifrices combined with fluoride varnish using a pH-cycling regimen. Seventy primary canines were covered with nail polish, leaving a 4×4 mm window on their buccal surface, and randomly assigned into 7 groups (n = 10): S: sound enamel not submitted to the pH-cycling regimen or treatment; N: negative control, submitted to the pH-cycling regimen without any treatment; D1 and D2: subjected to the pH-cycling regimen and treated twice daily with 1100 or 500 ppm F dentifrice, respectively; VF: fluoride varnish (subjected to F-varnish before and in the middle of the pH-cycling regimen); and VF+D1 and VF+D2. After 10 days, the teeth were sectioned, and enamel demineralization was assessed by cross-sectional hardness at different distances from the dental surface. Data were analyzed using a two-way ANOVA followed by Tukey's test. Dentifrice with 1100 ppm F and the combination of F-varnish with the dentifrices significantly reduced enamel demineralization compared with the negative control (p < 0.05), but the isolated effects of F-varnish and dentifrice with low concentration were not significant (p > 0.05). The effect of combining F-varnish with the dentifrices was not greater than the effect of the dentifrices alone (p < 0.05). The data suggest that the combination of F-varnish with dentifrices containing 500 and 1100 ppm F is not more effective in reducing demineralization in primary teeth than the isolated effect of dentifrice containing 1100 ppm F.