Exposure to second-hand smoke and breast cancer risk in non-smoking women: a comprehensive systematic review and meta-analysis.

Through the use of an innovative method to identify original publications, we conducted a meta-analysis of all epidemiological studies evaluating the association between second-hand smoke (SHS) exposure and breast cancer risk among female non-smokers published in English up to October 2022. Pooled relative risks (RR) were obtained through the use of random-effects models. Dose-response relationships were derived using log-linear functions. Out of 73 identified eligible studies, 63 original articles were included in the meta-analysis. The pooled RR for breast cancer for overall exposure to SHS was 1.24 (95% confidence interval, CI, 1.15-1.34, number of articles, n = 52). Regarding the setting of exposure, RRs were 1.17 (95% CI 1.08-1.27, n = 37) for SHS exposure at home, 1.03 (95% CI 0.98-1.08, n = 15) at the workplace, 1.24 (95% CI 1.11-1.37, n = 16) at home or workplace, and 1.45 (95% CI 1.16-1.80, n = 13) for non-specified settings. The risk of breast cancer increased linearly with higher duration (RR 1.29; 95% CI 1.04-1.59 for 40 years of SHS exposure, n = 12), intensity (RR 1.38; 95% CI 1.14-1.67 for 20 cigarettes of SHS exposure per day, n = 6), and pack-years (RR 1.50; 95% CI 0.92-2.45 for 40 SHS pack-years, n = 6) of SHS exposure. This meta-analysis shows a statistically significant excess risk of breast cancer in women exposed to SHS.

Dose-response Relationships Between Cigarette Smoking and Breast Cancer Risk: A Systematic Review and Meta-analysis.

BACKGROUND: The possible association between cigarette smoking and breast cancer risk has been quite controversial. METHODS: We conducted a systematic review and meta-analysis of all available observational studies published on the issue up to January 2020. Random-effects models were used to compute pooled relative risks (RRs) for cigarette smoking status and dose-risk relationships were evaluated using one-stage random-effects dose-response models. RESULTS: A total of 169 studies were selected, providing a pooled RR for breast cancer of 1.07 (95% confidence interval [CI], 1.05-1.10) for current, 1.08 (95% CI, 1.06-1.10) for former, and 1.09 (95% CI, 1.07-1.11) for ever smokers, compared to never smokers. Results were consistent in case-control and cohort studies. No meaningful differences were observed across strata of most covariates considered, nor according to relevant genetic mutations and polymorphisms (ie, BRCA mutation, N-acetyltransferase and glutathione S-transferase genotypes, and P53). Breast cancer risk increased linearly with intensity of smoking (RR 1.12; 95% CI, 1.08-1.16 for 20 cigarettes/day and 1.26; 95% CI, 1.17-1.36 for 40 cigarettes/day), and with increasing duration of smoking (RR 1.05; 95% CI, 1.03-1.08 for 20 years of smoking and 1.11; 95% CI, 1.06-1.16 for 40 years of smoking). CONCLUSION: The present large and comprehensive meta-analysis-conducted using an innovative approach for study search-supports the evidence of a causal role of tobacco smoking on breast cancer risk.

Importance of mitigation measures for hospital transmission of SARS-CoV-2 at the onset of the epidemic: the experience of Brescia, Northern Italy.

PURPOSE: Since the first Italian case of SARS-CoV-2 was detected in Lombardy (Northern Italy)  Italy quickly became one of the worst-affected European countries, with a severe impact on health-care workers (HCWs). In the first epidemic, HCWs accounted for 12% of all national COVID-19 cases. We evaluated the burden of COVID-19 among HCWs and other non-health-care workers (nHCWs) in a large Italian hospital. METHODS: From March 1st to May 31st 2020, we performed a retrospective study at ASST Civil Hospital, in the Province of Brescia, Lombardy. The study population included all hospital personnel (n = 9265), categorized by professional status. RESULTS: A SARS-CoV-2 test was performed in 3572 workers (38.5%), with a positive result in 552 (5.9% of all hospital personnel). The temporal trend of SARS-CoV-2 cases in hospital staff broadly reflected that in the community, with a great majority of infections occurred during March 2020 (87.7%). From April onward, a steep decrease of positive cases was observed among hospital personnel, while in the community the decrease was much slower. Medical doctors (8.9%) and nurses (8.5%) were the most affected professional categories with a significantly higher risk of SARS-CoV-2 infection (OR 1.436 and OR 1.410, respectively p < 0.0001). HCWs in COVID-19 units presented a significantly higher risk of infection compared to HCWs in non-COVID units (p < 0.001). CONCLUSION: HCWs were severely affected by the COVID-19 epidemic, probably associated with an overwhelming burden of work and lack of preparedness in prevention of nosocomial transmission of the infection. The rapid decrease of COVID-19 spread in the hospital, registered before the one in the community, suggests that the adopted preventive measures were effective.

Analysis of the direct economic impact of smoking-related hospitalizations in Italy.

INTRODUCTION: Tobacco-related diseases have a substantial economic impact in terms of medical expenses, loss of productivity, and premature death. Tobacco use is estimated to be responsible for more than 90000 deaths each year in Italy. We aimed to evaluate the annual direct economic impact on the National Health System of hospitalizations attributable to tobacco smoking in Italy. METHODS: We analyzed data from all the hospitalizations of patients aged ≥30 years that occurred in Italy for 12 selected tobacco-related diseases, during 2018. These diseases included oropharyngeal cancer, esophageal cancer, gastric cancer, lung cancer, pancreatic cancer, bladder cancer, laryngeal cancer, ischemic heart disease, stroke, diseases of arteries, arterioles, and capillaries, pneumonia and influenza, and chronic obstructive pulmonary disease. We obtained information on 984322 hospital discharge records, including each hospitalization's direct costs. Using relative risk estimates from the scientific literature, we computed the population attributable fraction for various tobacco-related diseases to estimate the economic impact attributable to tobacco smoking. RESULTS: One-third of all hospitalizations occurred in 2018 in Italy among people aged ≥30 years for 12 tobacco-related diseases were found to be attributable to smoking, accounting for a total cost of €1.64 billion. Among the diseases considered, those with the highest expenditures attributable to tobacco smoking were ischemic heart disease, cerebrovascular disease, and lung cancer, accounting for €556 million, €290 million, and €229 million, respectively. CONCLUSIONS: Tobacco has a substantial economic impact in Italy, accounting for around 6% of the total cost of hospitalizations in 2018. This figure is expected to be largely underestimated due to several conservative assumptions adopted in the statistical analyses. It is imperative to prioritize comprehensive tobacco control measures to counteract the huge healthcare costs due to tobacco smoking.

The effectiveness of Allen Carr's method for smoking cessation: A systematic review.

INTRODUCTION: Allen Carr's (AC) method is a pharmacotherapy-free approach to quit smoking that is delivered through seminars, online courses, or in the form of a book. It has gained popularity, but its effectiveness remains controversial due to a lack of scientific evidence. This systematic review aims to provide an updated overview of the current evidence on the effectiveness of the AC method. METHODS: We conducted a systematic literature review of all epidemiological studies evaluating the effectiveness of the AC method for smoking cessation, published in PubMed/MEDLINE and Embase up to March 2023. RESULTS: Among 34 original studies identified through the literature search, six met the inclusion criteria. These studies were published between 2006 and 2020, with sample sizes ranging from 92 to 620 participants. Of the six studies, two did not have a comparison group while four, including two randomized control led trials (RCT), had a comparison group. The included studies showed cessation rates for people who attended the seminars from 19% to 51%. An observational study found an odds ratio (OR) of abstinence for those attending AC single-session seminars of 6.52 (95% confidence interval, CI: 3.10-13.72) compared with controls with no treatment. One RCT found higher quit rates for AC single-session seminars compared with the online Irish National service (OR=2.26; 95% CI: 1.22-4.21). Another RCT reported no significant difference between AC single-session seminars and a specialist stopsmoking service. One single study on patients with head and neck disorders analyzed the effectiveness of reading the AC book, showing no significant results. CONCLUSIONS: The AC seminar may be an effective intervention for smoking cessation. This approach deserves further RCTs with large sample sizes to strengthen the evidence. Scant data are available on the effectiveness of reading the AC book.

Dose-risk relationships between cigarette smoking and cervical cancer: a systematic review and meta-analysis.

OBJECTIVE: Cervical cancer (CC) is the fourth most frequent cancer worldwide. Cigarette smoking has been shown to influence CC risk in conjunction with human papillomavirus (HPV) infection. The aim of this study is to provide the most accurate and updated estimate of this association and its dose-response relationship. METHODS: Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of studies published up to January 2021. Random effects models were used to provide pooled relative risks (RRs) of CC for smoking status. Dose-response relationships were evaluated using one-stage random effects models with linear or restricted cubic splines models. RESULTS: We included 109 studies providing a pooled RR of invasive CC and preinvasive lesions, respectively, of 1.70 [95% confidence interval (CI), 1.53-1.88] and 2.11 (95% CI, 1.85-2.39) for current versus never smokers, and, respectively, 1.13 (95% CI, 1.02-1.24) and 1.29 (95% CI, 1.15-1.46) for former versus never smokers. Considering HPV does not alter the positive association or its magnitude. Risks of CC sharply increased with few cigarettes (for 10 cigarettes/day, RR = 1.72; 95% CI, 1.34-2.20 for invasive CC and RR = 2.13; 95% CI, 1.86-2.44 for precancerous lesions). The risk of CC increased with pack-years and smoking duration and decreased linearly with time since quitting, reaching that of never smokers about 15 years after quitting. CONCLUSION: This comprehensive review and meta-analysis confirmed the association of smoking with CC, independently from HPV infection. Such association rose sharply with smoking intensity and decreased after smoking cessation.

The role of smoking in COVID-19 progression: a comprehensive meta-analysis.

The association between current smoking and coronavirus disease 2019 (COVID-19) progression remains uncertain. We aim to provide up-to-date evidence of the role of cigarette smoking in COVID-19 hospitalisation, severity and mortality. On 23 February 2022 we conducted an umbrella review and a traditional systematic review via PubMed/Medline and Web of Science. We used random-effects meta-analyses to derive pooled odds ratios of COVID-19 outcomes for smokers in cohorts of severe acute respiratory syndrome coronavirus 2 infected individuals or COVID-19 patients. We followed the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. PROSPERO: CRD42020207003. 320 publications were included. The pooled odds ratio for current versus never or nonsmokers was 1.08 (95% CI 0.98-1.19; 37 studies) for hospitalisation, 1.34 (95% CI 1.22-1.48; 124 studies) for severity and 1.32 (95% CI 1.20-1.45; 119 studies) for mortality. Estimates for former versus never-smokers were 1.16 (95% CI 1.03-1.31; 22 studies), 1.41 (95% CI: 1.25-1.59; 44 studies) and 1.46 (95% CI 1.31-1.62; 44 studies), respectively. Estimates for ever- versus never-smokers were 1.16 (95% CI 1.05-1.27; 33 studies), 1.44 (95% CI 1.31-1.58; 110 studies) and 1.39 (95% CI 1.29-1.50; 109 studies), respectively. We found a 30-50% excess risk of COVID-19 progression for current and former smokers compared with never-smokers. Preventing serious COVID-19 outcomes, including death, seems the newest compelling argument against smoking.

Global Prevalence and Incidence of Tinnitus: A Systematic Review and Meta-analysis.

Importance: To date, no systematic review has taken a meta-analytic approach to estimating the prevalence and incidence of tinnitus in the general population. Objective: To provide frequency estimates of tinnitus worldwide. Data Sources: An umbrella review followed by a traditional systematic review was performed by searching PubMed-MEDLINE and Embase from inception through November 19, 2021. Study Selection: Research data from the general population were selected, and studies based on patients or on subgroups of the population with selected lifestyle habits were excluded. No restrictions were applied according to date, age, sex, and country. Data Extraction and Synthesis: Relevant extracted information included type of study, time and location, end point, population characteristics, and tinnitus definition. The study followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Main Outcomes and Measures: Pooled prevalence estimates of any tinnitus, severe tinnitus, chronic tinnitus, and diagnosed tinnitus as well as incidence of tinnitus were obtained using random-effects meta-analytic models; heterogeneity between studies was controlled using the χ2 test, and inconsistency was measured using the I2 statistic. Results: Among 767 publications, 113 eligible articles published between 1972 and 2021 were identified, and prevalence estimates from 83 articles and incidence estimates from 12 articles were extracted. The pooled prevalence of any tinnitus among adults was 14.4% (95% CI, 12.6%-16.5%) and ranged from 4.1% (95% CI, 3.7%-4.4%) to 37.2% (95% CI, 34.6%-39.9%). Prevalence estimates did not significantly differ by sex (14.1% [95% CI, 11.6%-17.0%] among male individuals; 13.1% [95% CI, 10.5%-16.2%] among female individuals), but increased prevalence was associated with age (9.7% [95% CI, 7.4%-12.5%] among adults aged 18-44 years; 13.7% [95% CI, 11.0%-17.0%] among those aged 45-64 years; and 23.6% [95% CI, 19.4%-28.5%] among those aged ≥65 years; P < .001 among age groups). The pooled prevalence of severe tinnitus was 2.3% (95% CI, 1.7%-3.1%), ranging from 0.5% (95% CI, 0.3%-0.7%) to 12.6% (95% CI, 11.1%-14.1%). The pooled prevalence of chronic tinnitus was 9.8% (95% CI, 4.7%-19.3%) and the pooled prevalence of diagnosed tinnitus was 3.4% (95% CI, 2.1%-5.5%). The pooled incidence rate of any tinnitus was 1164 per 100 000 person-years (95% CI, 479-2828 per 100 000 person-years). Conclusions and Relevance: Despite the substantial heterogeneity among studies, this comprehensive systematic review on the prevalence and incidence of tinnitus suggests that tinnitus affects more than 740 million adults globally and is perceived as a major problem by more than 120 million people, mostly aged 65 years or older. Health policy makers should consider the global burden of tinnitus, and greater effort should be devoted to boost research on tinnitus.

A real world analysis of COVID-19 impact on hospitalizations in older adults with chronic conditions from an Italian region.

Healthcare delivery reorganization during the COVID-19 emergency may have had a significant impact on access to care for older adults with chronic conditions. We investigated such impact among all adults with chronic conditions aged ≥ 65 years, identified through the electronic health databases of two local health agencies-ATS Brianza and ATS Bergamo-from the Lombardy region, Italy. We considered hospitalizations for 2020 compared to the average 2017-2019 and quantified differences using rate ratios (RRs). Overall, in 2017-2019 there were a mean of 374,855 older adults with  ≥ 1 chronic condition per year in the two ATS and 405,371 in 2020. Hospitalizations significantly decreased from 84,624 (225.8/1000) in 2017-2019 to 78,345 (193.3/1000) in 2020 (RR 0.86). Declines were reported in individuals with many chronic conditions and for most Major Diagnostic Categories, except for diseases of the respiratory system. The strongest reductions were observed in hospitalizations for individuals with active tumours, particularly for surgical ones. Hospitalization rates increased in individuals with diabetes, likely due to COVID-19-related diseases. Although determinants of the decrease in demand and supply for care among chronic older adults are to be further explored, this raises awareness on their impacts on chronic patients' health in the medium and long run.

Rationale and pre-clinical evidences for the use of autologous cartilage micrografts in cartilage repair.

BACKGROUND: The management of cartilage lesions is an open issue in clinical practice, and regenerative medicine represents a promising approach, including the use of autologous micrografts whose efficacy was already tested in different clinical settings. The aim of this study was to characterize in vitro the effect of autologous cartilage micrografts on chondrocyte viability and differentiation and perform an evaluation of their application in racehorses affected by joint diseases. MATERIALS AND METHODS: Matched human chondrocytes and micrografts were obtained from articular cartilage using Rigenera® procedure. Chondrocytes were cultured in the presence or absence of micrografts and chondrogenic medium to assess cell viability and cell differentiation. For the pre-clinical evaluation, three racehorses affected by joint diseases were treated with a suspension of autologous micrografts and PRP in arthroscopy interventions. Clinical and radiographic follow-ups were performed up to 4 months after the procedure. RESULTS: Autologous micrografts support the formation of chondrogenic micromasses thanks to their content of matrix and growth factors, such as transforming growth factor ß (TGFß) and insulin-like growth factor 1 (IGF-1). On the other hand, no significant differences were observed on the gene expression of type II collagen, aggrecan, and SOX9. Preliminary data in the treatment of racehorses are suggestive of a potential in vivo use of micrografts to treat cartilage lesions. CONCLUSION: The results reported in this study showed the role of articular micrografts in the promoting chondrocyte differentiation suggesting their potential use in the clinical practice to treat articular lesions.

Regenerative medicine for the definitive surgical repair of pilonidal sinus. A new method of wound reconstruction.

OBJECTIVE: A retrospective analysis of patients undergoing surgery for complex (> or =3 tracks) or recurrent pilonidal sinus (PS) was performed; the results of this clinical experience were compared with an original method of primary wound closure, coupling a "tension-free" technique of wound reconstruction with autologous cryoplatelet gel application, in order to improve the wound healing process and reduce the postoperative disability period. PATIENTS AND METHODS: The retrospective analysis included 30 patients undergoing surgery for PS between January 2003 and May 2005: in the first group of 15 consecutive patients, the wound was left open to close secondarily while in the remaining 15 patients, primary closure by means of a "tension-free" technique of wound reconstruction was attempted. Between June 2005 and May 2006, another subset of 15 patients was prospectively recruited, coupling the "tension-free" technique of wound reconstruction with autologous cryoplatelet gel application. RESULTS: In the first group of patients, median postoperative disability accounted for 65 days with one recurrence. In the second group, primary healing was achieved in 11 patients, with a median postoperative disability of 28 days; two recurrences did occur. In the third group of patients, primary healing was achieved in all patients within 14 to 29 days, and no recurrence has yet been detected. CONCLUSION: Short follow-up notwithstanding, the simplicity of the operation, the use of autologous products and the minimal postoperative disability with complete wound healing suggest that this new approach may represent a useful alternative to current surgical techniques for PS excision.

Clinical applications of autologous cryoplatelet gel for the reconstruction of the maxillary sinus. A new approach for the treatment of chronic oro-sinusal fistula.

The authors report their clinical experience regarding an original method of surgical repair of oro-sinusal communications. From September 1999 to December 2003, 13 patients (7 male and 6 female patients; mean age: 52 years, range: 24-68 years) underwent surgical repair of an oro-antral fistula by means of cryoplatelet gel: in three patients, it was mixed with bioglass granules; in two, it was mixed with Bioss; in three, it was mixed with particulate bone extracted by means of a bone grafter from the oral cavity close to the operative site, with addition of demineralised bovine bone; in three, it was used together with porose hydroxyapatite, and in two patients the cryoplatelet gel was used only. No postoperative complication was reported; primary wound healing was achieved within seven to nine days. A bony orthopantoscintigraphy was performed a few months following the operative procedure, showing an active osteogenic process. In eight patients, a CT was performed after 8 to 12 months from the operation, showing a normal pneumatization with reconstruction of the floor of the maxillary sinus. Although preliminary, these findings seem to suggest that the use of bioengineered materials coupled with growth factors and osteoprogenitor cells may represent a valuable alternative to autologous bone transplantation for the reconstruction of the maxillary sinus.

Cryosurgery for advanced malignant melanoma of the facial skin. A case report.

BACKGROUND: Cryosurgery is safely employed for the treatment of skin precancerous and malignant lesions of the head and neck in selected patients. The case of a 101-year-old female patient with advanced malignant melanoma of the facial skin, undergoing cryosurgery, is reported in order to assess the feasibility and tolerability of the technique, as well as the biological implications of cryosurgical treatment in this specific neoplasm. CASE REPORT: A 101-year-old woman, with a large (pT4b N0 M0) cutaneous melanoma of the facial skin on the right cheek, was treated at the Division of Surgical Oncology of the National Cancer Research Institute, Italy, from June to August 2003. The treatment was accomplished by means of serial cryosurgical applications which were performed within three months; the bulk of the lesion was cryotreated with a liquid nitrogen cryoprobe, while the residual disease was treated with a nitrous protoxide cryoprobe, by means of the insertion technique. The treatment was well tolerated, with a good aesthetic result, and the patient is recurrence- and distant-disease-free two years after the initial cryosurgical application. CONCLUSION: Cryosurgery is feasible in the treatment of head and neck melanoma, mostly for mucosal melanomas and cutaneous lesions in anatomically critical sites, as well as in high-risk surgical patients. Here, a good aesthetic result was obtained in a very elderly patient with a large cutaneous melanoma of the facial skin, avoiding skin flap transposition for tissue repair and postoperative complications (e.g., serious bleeding or postoperative pain), with a satisfactory functional and oncological outcome at two years.

The use of platelet-rich plasma gel in patients with mixed tumour undergoing superficial parotidectomy: a randomized study.

BACKGROUND/AIM: Salivary gland tumors are mostly benign tumors. Whether a more conservative surgical approach at greater risk of recurrence, or a more radical intervention with an increased risk of facial paralysis is warranted is still under discussion. Our study addresses the opportunity for improving surgical outcome by employing platelet-rich plasma (PRP) gel at the surgical site. PATIENTS AND METHODS: Twenty consecutive patients undergoing superficial parotidectomy were randomized and assigned to two groups, one with and one without PRP gel. Many parameters were evaluated after surgery and during follow-up, such as the duration of hospitalization, facial nerve deficit, onset of Frey's syndrome, relapse, cosmetic results, presence of keloid or scar depressions, behavior of several facial muscles. RESULTS: Our explorative analysis suggests a positive effect of PRP on surgical outcome in patients undergoing parotidectomy, whereas no negative effects were detected. CONCLUSION: This work suggests that administration of PRP in patients undergoing parotidectomy is beneficial.

Regenerative medicine for the treatment of Teno-desmic injuries of the equine. A series of 150 horses treated with platelet-derived growth factors.

BACKGROUND/AIM: The aim of the present study was to evaluate the safety and the clinical outcome of platelet-rich plasma for the treatment of teno-desmic injures in competition horses. PATIENTS AND METHODS: From January 2009 to December 2011, 150 sport horses suffering from teno-desmic injuries were treated with no-gelled platelet-concentrate. RESULTS: No horse showed any major adverse reaction as a result of the procedure. Full healing was obtained for 81% of the horses. Twelve percent had clinical improvement and only 7% a failure. Eight percent of cases of relapse were observed. No statistically significant correlation existed between clinical outcome and the area of the lesion. A statistically significant correlation existed between the clinical outcome and the age of the horse. CONCLUSION: Treatment with platelet-derived growth factors leads to the formation of a tendon with normal morphology and functionality, which translate in the resumption of the agonistic activity for the horses we treated.

Regenerative Surgery for the Definitive Repair of a Vasculitic Nonhealing Ulcer Using Platelet-derived Growth Factors and Noncultured Autologous Cell Suspension.

SUMMARY: Vasculitic ulcers are caused by numerous disorders and may be chronic if not well treated. Various modalities of treatment, both medical and surgical, are available. We describe the case of a 63-year-old patient with a vasculitic ulcer treated with platelet-derived growth factors and noncultured autologous cell suspension collected by an innovative single-use device (ReCell).

Association of vacuum-assisted closure and platelet gel for the definitive surgical repair of an enterocutaneous fistula: a case report.

BACKGROUND: Regenerative surgery deals with damaged tissue via endogenous cell activation or through autologous cell implantation. Several clinical applications employing cell infusions, platelet gel (PG), or both, are currently applied in cases in which no other therapy is application. The vacuum-assisted closure (VAC) system is a non invasive device used in the management of complicated wounds, which creates sub-atmospheric pressure promoting the wound healing process. PATIENTS AND METHODS: We describe the case of a 75-year-old woman who underwent several surgical interventions and presented a non-healing ileo-cutaneous fistula. All standard procedures in order to treat the trauma failed, so a treatment associating VAC and PG was performed. DISCUSSION AND CONCLUSION: VAC and PG represent promising opportunities for the treatment of difficult wounds. In this case, the association of regenerative medicine using homologous PG to the VAC therapy was employed in order to enhance the effect of both techniques on tissue repair.

Oral cancer genesis and progression: DNA near-diploid aneuploidization and endoreduplication by high resolution flow cytometry.

Oral potentially malignant lesions (OPMLs) with dysplasia and aneuploidy are thought to have a high risk of progression into oral squamous cell carcinomas (OSCCs). Non-dysplastic "oral distant fields" (ODFs), characterized by clinically normal appearing mucosa sited at a distance from co-existing OPMLs, and non-dysplastic OPMLs may also represent an early pre-cancerous state. ODFs, OPMLs without and with dysplasia and OSCCs were investigated by high resolution DNA content flow cytometry (FCM). ODFs and OPMLs without dysplasia were DNA aneuploid respectively in 7/82 (8.5%) and 25/109 (23%) cases. "True normal oral mucosa" and human lymphocytes from healthy donors were DNA diploid in all cases and were used as sex specific DNA diploid controls. Dysplastic OPMLs and OSCCs were DNA aneuploid in 12/26 (46%) and 12/13 (92%) cases. The DNA aneuploid sublines were characterized by the DNA Index (DI not =1). Aneuploid sublines in ODFs and in non-dysplastic and dysplastic OPMLs were near-diploid (DI<1.4) respectively in all, 2/3 and 1/3 of the cases. DNA aneuploid OSCCs, instead, were characterized prevalently by multiple aneuploid sublines (67%), which were commonly (57%) high-aneuploid (DI> or =1.4). DNA near-diploid aneuploid sublines in ODFs and OPMLs appear as early events of the oral carcinogenesis in agreement with the concept of field effect. Near-diploid aneuploidization is likely to reflect mechanisms of loss of symmetry in the chromosome mitotic division. High DNA aneuploid and multiple sublines in OPMLs with dysplasia and OSCCs suggest, instead, mechanisms of "endoreduplication" of diploid and near-diploid aneuploid cells and chromosomal loss. High resolution DNA FCM seems to enable the separation of subsequent progression steps of the oral carcinogenesis.