Cervical Intraepithelial Neoplasia Grade 3 (CIN3) in Women Younger than 30 Years Was Significantly Associated with HPV16/18 Genotypes.

BACKGROUND: The objective of the present study is to investigate the age-specific distribution of HPV genotypes in CIN3 lesions in screened unvaccinated women. These data are essential to optimize current and future screening programs. METHODS: A multicenter retrospective study was conducted. A total of 408 unvaccinated women with positive histology and a high-risk HPV genotype were enrolled. Each woman at baseline had HPV DNA testing and HPV genotyping, and all women underwent targeted biopsy and/or treatment with a loop electrosurgical excision procedure (LEEP) before entering the study. We divided the genotypes into HPV16/18 and HPV non-16/18 (HPV31/33/45/35/39/51/52/58/59/66/68). Women were divided into increasing age categories: <30, 30-44, and ≥45. RESULTS: The percentage of CIN3 associated with HPV16/18 is maximum in women under 30 years of age (85.1%), drops to 75.6% in women aged between 30 and 44 years, and up to 47.2% in women over 45 years. CIN3 in women younger than 30 years was significantly associated with HPV16/18 genotypes (p = 0). DISCUSSION: The data from the present study suggest that the risk of CIN3 is related to the woman's age and hr HPV genotype. The data highlight two different types of CIN3: a more frequent type, related to HPV16/18, which develops rapidly and in young women, and another, relating to non-16/18 HPV, which develops later at an advanced age and slowly, through low-grade lesions.

The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3.

The purpose of this study was to evaluate the incidence of AIS and AC in the histological cone of women treated for CIN3. Furthermore, through the study of the specific HR HPV genotypes, we obtained more information on the possible different nature between the single CIN3 lesion and the CIN3 coexisting with the glandular lesion. METHODS: A sample of 414 women underwent LEEP for CIN3. The study sample consisted of 370 women with a CIN3 lesion alone and 44 women with a CIN3 lesion coexisting with AIS or adenocarcinoma. We studied the individual HR HPV genotypes and their frequency in the two groups under study. Furthermore, the therapeutic results and follow-ups for the population were studied on the entire study sample. RESULTS: In patients with a single CIN3 lesion, 11 high-risk genotypes were detected; in patients with CIN3 associated with AIS or AC, only 4 different genotypes were detected (16, 18, 45, 33). Overall, the frequency of HPV 18 was significantly higher in CIN3 coexisting with AIS compared to solitary CIN3 lesions, χ2 = 27.73 (p < 0.001), while the frequency of other high-risk genotypes was significantly higher in patients with a single CIN3 than in patients with CIN3 coexisting with AIS. In our study population, mixed lesions (CIN3 coexisting with AIS), unlike their squamous counterparts (single CIN3 lesions), were characterized by skip lesions, which demonstrate more aggressive behavior and a higher rate of viral persistence and recurrence. CONCLUSION: A relatively high rate (10.7%) of AIS-AC was found in women treated for CIN3. Our study confirms the multifocal biological nature of the CIN3 lesion coexisting with AIS compared to the single CIN3 lesion. All this justifies the different treatments to which CIN3 lesions coexisting with AIS are addressed; in fact, the latter are treated with hysterectomy, while CIN3 is treated with conization alone.

Overexpression of E6/E7 mRNA HPV Is a Prognostic Biomarker for Residual Disease Progression in Women Undergoing LEEP for Cervical Intraepithelial Neoplasia 3.

The risk of overtreatment or not treating an occult carcinoma exists in women at risk of residual disease after a LEEP excision for CIN3. Our goal was to discover an efficient method to select patients requiring a second LEEP from those requiring a FU only through an mRNA-detection test. In a population of 686 women undergoing a LEEP excision for CIN 3, we selected 285 women at risk of residual disease and subjected them to a search for E6/E7 mRNA HPV. The women with negative mRNA were subjected to a follow up, while the women with positive mRNA were subjected to a second LEEP. The histological examination of the second cone revealed 120 (85.7%) cases of residual disease in the mRNA-positive women: 40 cases of CIN2, 51 cases of CIN3, 11 cases of squamous microinvasive carcinoma, 7 cases of squamous carcinoma, 9 cases of AIS (adenocarcinoma in situ) and 2 cases of adenocarcinoma. Among the mRNA-negative women undergoing a follow up, there were only five cases of residual disease. During the follow-up period of about 6 years, we witnessed the regression of the residual disease and the elimination of the virus, just as predicted by the negative result of the mRNA test. Testing patients for E6/E7 mRNA allowed us to identify women with residual disease (CIN2+) and treat them appropriately.

Oral HPV Infection in Women with HPV-Positive Cervix Is Closely Related to Oral Sex.

The oral transmission of HPV and, consequently, the risk of oral cancer has increased in the last years. Oral sex has often been implicated among the risk factors for oral HPV infections, however, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. The present study aimed to evaluate the coexistence of papilloma virus, at the levels of the oral and genital mucosa, in women with a histologically confirmed HPV lesions (and a positive HPV test) at the genital level and a negative HPV control group. We also evaluated how some risk factors, such as smoking, the number of partners, age, and sexual habits can influence the possible presence of the virus itself in the oropharynx of the same women. In total, 117 unvaccinated women aged between 18 and 52 were enrolled. We found that the prevalence of oral HPV infection was high among the women with concomitant genital HPV infection (22%) compared to the HPV-negative women (0%), and the estimated odds ratio was 17.36 (95% CI: 1.02, 297.04). In none of the women with oral HPV did we find any relevant clinical lesions. The potential risk factors for HPV infections in the oropharynx and genitals were analyzed based on questionnaire responses. A multivariate analysis showed that genital HPV infections were significantly associated with a number of sexual partners > 10 (OR 138.60, 95% CI: 6.04-3181.30, p < 0.001), but the data also referred to having between 3-5 or 6-10 partners as being significant, as were a high level of education (OR 6.24, 95% CI: 1.67-4.23.26 p = 0.003), a frequency of sexual intercourse >10 (OR 91.67 95% CI: 3.20-2623.52, p = 0.004), oral sex (OR 6.16, 95% CI: 1.22-31.19, p = 0.014), and >20 cigarettes/day (OR 6.09 95% CI: 1.21-30.61, p = 0.014). Furthermore, being "separate" and having multiple sexually transmitted diseases were also significantly associated with genital HPV infection. In contrast, oral HPV infections were significantly associated with women aged 36 to 50 years (OR 27.38, 95% CI: 4.37-171.37; p = 0.000202) and oral sex (OR 95.5, 95% CI: 5.13-1782.75, p = 0.001126).Additionally, being separate, being cohabitant, lifetime sexual partners of >10, 3-5 lifetime sexual partners, <20 years of age, >10 sexual intercourse per month, occasional and regular anal sex, >20 cigarettes per day, a history of sexually transmitted disease (herpes and multiple), and having a history of genital warts were significant. Screening and early diagnosis are considered to be practically unfeasible for this category of cancer, given the lack of visible lesions; the 9-valent HPV vaccine remains the only means that could help to successfully counter the growing incidence of oral squamous cell carcinoma.

Use of a Combined Laryngo-Bronchoscopy Approach in Difficult Airways Management: A Pilot Simulation Study.

OBJECTIVE: There are several airway devices available for difficult tracheal intubation (DTI) management, but the failure rate remains high. The use of laryngoscopy to facilitate the fibreoptic-bronchoscope intubation (CLBI) has been increasingly reported in DTI situations, but it has not been formally studied yet. METHODS: We designed a single-centre simulation study on DTI (neck rigidity and tongue oedema) comparing three techniques: direct laryngoscopy (DL), video-laryngoscopy (VLS) and CLBI. Eighteen anaesthesiologists naïve to VLS/CLBI approaches, participated in the study. The primary outcome was the intubation rate at the first attempt. Secondary outcomes were an overall time-to-intubate (TTI) and time-to-ventilate (TTV), success at the second and third attempt and ease of intubation as evaluated by a subjective 5-point Likert scale. RESULTS: The CLBI technique had a higher success rate at the first attempt than DL (66% vs 22%, p=0.007), while VLS did not (44%, p=0.16). A trend towards higher success at the third attempt was found for both VLS and CLBI vs DL (p=0.07 and p=0.06, respectively). The VLS had a shorter overall TTV than DL (88±60 vs 121±59 sec, respectively, p=0.04) and a trend towards a shorter TTI (81±61 vs 116±64 sec, respectively, p=0.06). The CLBI approach showed a non-significantly lower TTI/TTV as compared to DL (p=0.10 and p=0.16, respectively). Anaesthesiologists judged that the intubation with VLS (3.7±1.0) and CLBI (3.8±1.0) was easier than with DL (1.7±0.8, both p<0.001). CONCLUSION: In a simulated DTI scenario, CLBI had a higher success rate at the first attempt than DL, while VLS did not. By the third attempt, both rescue techniques had a trend towards a higher success rate than DL. The CLBI technique seems a promising alternative for the management of DTI.

Retroaortic closure of thoracic duct in the management of persistent chylothorax: a case report.

BACKGROUND: Chylothorax is a life-threatening pathological condition associated with significant morbidity and mortality. If chyle leakage does not close spontaneously with medical therapy, surgical treatment is inevitable. Herein, we reported a case of spontaneous persistent chylothorax from mediastinal seminoma that was successfully closed between the descending thoracic aorta, and the vertebral column through a left mini-thoracotomy. CASE PRESENTATION: A 24-year old man with mediastinal seminoma was referred to our attention for management of high output persistent chylothorax (> 800 ml/24 h for 30 days) that did not close with conservative treatment. As the leak was isolated within left upper chest cavity, we planned to close the thoracic duct via Poirier's triangle by uniportal thoracoscopy. However, the long conservative treatment favoured the formation of multiple, tenacious, and bleeding adhesions that made unfeasible thoracoscopy. A conversion to mini-thoracotomy was performed; by the incision of the posterior parietal pleura, the thoracic duct was isolated and ligated behind the thoracic aorta, in an anatomical space delimited by the 4th and the 5th posterior intercostal arteries and the vertebral column. CONCLUSIONS: Complete resolution of chylothorax was obtained the day after. Patient was discharged on post-operative day 5, and no recurrence was observed during the follow-up.

Uniportal thoracoscopy combined with laparoscopy as minimally invasive treatment of esophageal cancer.

A 67-year-old man was referred to our attention for management of esophageal adenocarcinoma, localized at the level of the esophagogastric junction and obstructed the 1/3 of the esophageal lumen. Due to the extension of the disease (T3N1M0-Stage IIIA), the patient underwent neo-adjuvant chemo-radiation therapy and he was then scheduled for a minimally invasive surgical procedure including laparoscopic gastroplasty, uniportal thoracoscopic esophageal dissection and intrathoracic end-to-end esophago-gastric anastomosis. No intraoperative and post-operative complications were seen. The patient was discharged in post-operative day 9. Pathological study confirmed the diagnosis of adenocarcinoma (T2N1M0-Stage IIB) and he underwent adjuvant chemotherapy. At the time of present paper, patient is alive and well without signs of recurrence or metastasis. Our minimally approach compared to standard open procedure would help reduce post-operative pain and favours early return to normal activity. However, future experiences with a control group are required before our strategy can be widely used.

Resection of esophageal diverticulum through uniportal video-assisted thoracoscopic surgery.

Open surgery remains the standard strategy for management of esophageal diverticulum in symptomatic patients. However, in the last years an increasing number of minimally invasive approaches have been proposed for this issue in order to reduce the surgical trauma and favor a fast return to daily activity. Herein, we describe a novel technique as uniportal video-assisted thoracoscopic surgery (VATS) for performing resection of esophageal diverticulum. This procedure was successfully carried out in three consecutive patients with giant mid-esophageal diverticulum (mean size: 6.5±0.5 cm). The mean post-operative time was 121±10 minutes. The chest drain was removed 48 hours later in all cases and the mean length of hospital stay was 9±1 days. No intraoperative neither postoperative complications were found in all patients but one. He had a small fistula 15 days later that was successfully treated with stent insertion. No recurrence of diverticulum was seen in all cases. Uniportal VATS is a feasible procedure that in theory could reduce the surgical trauma compared to standard open approach. However, future prospective studies should corroborate our impression before it can be recommended as acceptable therapy.

Uniportal bilateral video-assisted sequential thoracoscopic extended thymectomy.

Standard video-assisted thoracoscopic surgery has been reported as a minimally invasive approach alternative to sternotomy for management of myasthenia gravis (MG) associated with thymoma or thymic hyperplasia. Uniportal video-thoracoscopy is an evolution of standard multi-portal video-thoracoscopy for management of several thoracic diseases but its role for resecting mediastinal tumor remains under-evaluated. Herein, we describe our experience with bilateral uniportal thoracoscopic sequential extended thymectomy with case and video illustrations.

Four-step local anesthesia and sedation for thoracoscopic diagnosis and management of pleural diseases.

STUDY OBJECTIVES: Most thoracic surgeons perform thoracoscopy under general anesthesia using a double-lumen endotracheal tube. We describe our own technique for performing thoracoscopy under local anesthesia and sedation. DESIGN, SETTING, PATIENTS: Forty-five patients underwent the procedure under local anesthesia and sedation (mean age, 64 years; age range, 40 to 92 years). A known history of cancer was present in 12 patients. American Society of Anesthesiology score was I in 1 patient, II in 16 patients, III in 22 patients, IV in 5 patients, and V in 1 patient. Premedication was comprised of droperidol, 5 mg, and atropine, 0.5 mg, administered 20 min before the scheduled operating room time. Sedation was maintained by diazepam injection, 3 mg. Four-step local anesthesia in the planned intercostal space using 10 mL of ropivacaine, 7.5 mg/mL, was performed. RESULTS: Mean operative time was 45.7 min (range, 20 to 90 min); mean time of anesthesia was 71.3 min (range, 30 to 150 min). Among patients with pleural effusion, 23 effusions were simple and 16 effusions were complex. Talc was administrated in 28 patients. Complications were intraoperative bleeding (one patient), hyperpyrexia (eight patients), and atrial fibrillation (two patients). The mean time for removal of the chest drain was 5.6 days (range, 2 to 13 days). Postoperative hospital stay was 6.4 days (range, 2 to 14 days). No hospital mortality occurred. Follow-up is complete in all patients (mean, 92.8 days; range, 31 to 270 days). CONCLUSION: Four-step local anesthesia and sedation is a simple and effective method of performing a video-assisted thoracic procedure to diagnose and treat simple thoracic pathologies.