Transtracheal thoracic natural orifice transluminal endoscopic surgery (NOTES) in a swine model.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has the potential to be the final frontier in minimally invasive procedures in thoracic surgery. In order for thoracic pleural NOTES to 1 day be ready for clinical trials, each step of the procedure must be independently evaluated for both safety and efficacy. The aim of this study was to evaluate the trachea as a portal of entry for thoracic NOTES. METHODS: Eight 40-kg swine underwent right thoracic pleuroscopy in a survival model. In order to avoid inadvertent injury to the superior vena cava, endobronchial ultrasound was employed to select the location of airway incision. A 7-mm linear incision was then performed at the chosen location using an endoscopic electrocautery needle knife through a therapeutic flexible videobronchoscope. The mediastinal fat and parietal pleura were then dissected with electrocautery, and complete right pleuroscopy was performed. The tracheal and mediastinal portal of entry were then sealed with 1-2 cc of fibrin sealant. The pigs were kept alive for 21 days postoperatively. Postmortem diagnostic bronchoscopy was performed to assess tracheal healing. All tracheal specimens underwent histologic examination for healing and signs of mediastinal infection. RESULTS: Thoracic NOTES procedures on all eight pigs were successful. There were no intraoperative complications except for one minor bleeding episode within the mediastinal dissection site which stopped spontaneously. Two pigs died from severe laryngospasm in the early postoperative period. Six pigs survived for 21 days post-procedure and experienced uneventful postoperative courses. Postmortem examination demonstrated complete tracheal healing with appropriate scarring in all pigs. CONCLUSIONS: The trachea appears to be a safe port of entry for thoracic NOTES procedures in a swine model. Smaller tracheal incisions followed by balloon dilatation are associated with less postoperative morbidity and mortality. Tracheal incisions sealed with fibrin sealant healed rapidly and without signs of mediastinal infection. This procedure represents a work in progress and is not yet ready for human trials.

Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with cobas 4800 HPV and Hybrid Capture 2 tests for detection of high-grade lesions of the uterine cervix.

The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (P = 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy.

HAART and progression to high-grade anal intraepithelial neoplasia in men who have sex with men and are infected with HIV.

BACKGROUND: Human immunodeficiency virus (HIV)-seropositive men who have sex with men (MSM) are at risk for anal intraepithelial neoplasia (AIN) and cancer. The goal of this study was to identify risk factors associated with high-grade AIN (AIN-2,3) in HIV-positive MSM, including the receipt of highly active antiretroviral therapy (HAART). METHODS: A cohort study involving 247 HIV-seropositive MSM receiving HAART or initiating HAART was followed up every 6 months for 3 years with human papillomavirus (HPV) testing and high-resolution anoscopy to identify predictors of AIN-2,3 by Cox regression analysis and period prevalence logistic regression. RESULTS: AIN-2,3 was observed during the study in 132 (53%) of 247 participants. The progression rate to AIN-2,3 from a lesser abnormality at baseline was 12.8 cases per 1000 person-months (95% confidence interval [CI], 9.8-16.5 cases per 1000 person-months). The risk of AIN-2,3 increased with age (odds ratio [OR], 3.09 [95% CI, 1.12-8.52] for men 40-49 years of age and 4.78 [95% CI, 1.29-17.73] for men >50 years of age, compared with men <40 years of age) and for men whose CD4+ cell counts were <50 cells/mm(3) before starting HAART (OR, 14.40 [95% CI, 1.45-143.58]). Men who had been receiving their current HAART regimen for >4 years had a marginally significant lower risk of AIN-2,3 after adjustment for HPV (OR, 0.28 [95% CI, 0.07-1.06]) compared with those treated for <4 years. Anal HPV type 16 (HPV16) or type 18 (HPV18) infections (OR, 14.18; [95% CI, 3.51-57.32]) and HPV16 and HPV18 co-infection (OR, 31.03 [ 95% CI, 5.68-169.60]) were strongly associated with progression to AIN-2,3. CONCLUSION: HPV16 and HPV18 infections and a low nadir CD4+ cell count increase the risk of AIN-2,3. Receiving the same HAART regimen for >4 years may contribute some benefit against AIN-2,3.

Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with Amplicor HPV and Hybrid Capture 2 assays for detection of high-grade lesions of the uterine cervix.

Up to 20% of women having a cytology smear showing atypical squamous cells of undetermined significance (ASC-US) and infected with high-risk human papillomavirus (HR HPV) have high-grade cervical intraepithelial neoplasia (CIN 2/3). Results obtained with the Amplicor HPV and Hybrid Capture 2 (HC-2) assays for HR HPV DNA detection in women referred to colposcopy for an ASC-US smear were compared. Cervical samples in PreservCyt were tested for the presence of 13 HR HPV types with HC-2, with Amplicor at three cutoffs for positivity (0.2, 1.0, and 1.5 optical density units), and for 36 genotypes with the Linear Array (LA). Of 396 eligible women, 316 did not have CIN, 47 had CIN 1, 29 had CIN 2/3, and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 164 (41.4%) samples with HC-2 and Amplicor HPV (cutoff, 0.2), respectively (P = 0.01). Overall, 112 specimens were positive and 215 were negative with the HC-2 and Amplicor HPV assays (agreement of 82.6%; 95% confidence interval [CI], 78.5 to 86.0). The clinical sensitivity and specificity of Amplicor HPV at cutoffs of 0.2, 1.0 and 1.5 and of HC-2 for detection of CIN 2/3 were 89.7% (95% CI, 72.8 to 97.2) and 62.5% (95% CI, 57.5 to 52.4), 89.7% (95% CI, 72.8 to 97.2) and 64.5% (95% CI, 59.4 to 69.2), 89.7% (95% CI, 72.8 to 97.2) and 64.7% (95% CI, 59.7 to 69.5), and 93.1% (95% CI, 77.0 to 99.2) and 72.2% (95% CI, 67.4 to 76.5), respectively. Both HR HPV detection tests identified women with ASC-US who would benefit the most from colposcopy. Women with persistent HR HPV infection need further investigation despite a first normal colposcopy.

Heat production during pulmonary artery sealing with energy vessel-sealing devices in a swine model.

OBJECTIVES: Energy vessel-sealing devices are being increasingly utilized to seal pulmonary artery (PA) branches during lobectomy. Heat from these devices can potentially injure surrounding tissues. We evaluated heat production from devices in a live animal model. METHODS: PA branches were sealed in pigs with 4 energy vessel-sealing devices: 2 ultrasonic (US), 1 advanced bipolar or 1 mixed US and bipolar (mixed) device. Thermocouples were implanted in tissue surrounding the PA branch being sealed to measure tissue temperature. A thermal camera measured the sealing site and the temperatures of the instruments. Pathological analysis was performed on PA stumps to identify thermal damage. RESULTS: A total of 37 PA branches were sealed in 4 pigs. Maximum tissue heat measured by the thermocouples for the 2 US, advanced bipolar and mixed devices was 42, 39, 42 and 46°C, respectively. The mean tissue temperatures at the site of the sealing measured with the thermal camera were 78, 75, 70 and 82°C (P = 0.834) and the mean instrument blade temperatures were 224, 195, 83 and 170°C (P = 0.000005) for the 2 US, advanced bipolar and mixed devices, respectively. The mean diameter of the region with tissue reaching 60°C or more measured with the thermal camera was between 4 and 6 mm for the 4 devices (P = 0.941). On pathological analysis, PA stumps had either thermal damage on the adventitia and external media (26/37) or transmural damage (11/37) at 1 mm from sealed site. CONCLUSIONS: A 3-mm safety margin between the instrument blades and vital structures is recommended. Instrument blades can reach high temperatures that may cause tissue damage.

Aggressive angiomyxoma of the vulva: a case report and review of the literature.

BACKGROUND: Aggressive angiomyxoma is a variant of myxoid neoplasms of the female pelvic soft parts. The term "aggressive" refers to the tumor's locally infiltrative and recurrent nature because distant metastases are rare. CASE: A 25-year-old woman presented with a 9-month history of an asymptomatic, polypoid mass arising from the right anterior labium minus. Histopathological and radiological examinations were consistent with a diagnosis of aggressive angiomyxoma. The patient was treated with a GnRH agonist followed by surgical excision. CONCLUSION: We highlight the novel use of a GnRH agonist as a neoadjuvant to surgery in aggressive angiomyxoma to shrink the tumor preoperatively and decrease surgical morbidity.

Pulmonary Artery Sealing With an Ultrasonic Energy Device in Video-Assisted Thoracoscopic Surgery Lobectomy: An Animal Survival Study.

BACKGROUND: Pulmonary artery (PA) sealing in video-assisted thoracoscopic surgery (VATS) lobectomy is typically accomplished using vascular endostaplers. Endostaplers may be associated with iatrogenic PA branch injury, especially in short, small PA branches. We evaluated PA branch sealing with the HARMONIC ACE +7 (ACE) shears (Ethicon, Cincinnati, OH) in VATS lobectomy in a canine survival model. METHODS: Ten adult dogs underwent VATS lobectomy. Standard VATS lobectomy operative technique was used for the entire operation, except for PA branch sealing. The ACE was used for all PA branch sealing. Dogs were kept alive for 30 days. RESULTS: The 10 dogs underwent VATS right upper (n = 5) and right lower (n = 5) lobectomy. The ACE was used to seal 21 PA branches. No PA branch was divided with an endostapler. There were no intraoperative complications or conversions to thoracotomy. Mean in vivo PA diameter was 5.6 mm (range, 2 to 12 mm). One 10-mm PA branch had a partial seal failure immediately at the time of sealing. The device was reapplied on the stump, and the PA branch was successfully sealed. All dogs survived 30 days without hemothorax. Necropsy at 30 days did not reveal any signs of postoperative bleeding. Pathology of the sealed PA branches at 30 days revealed fibrosis, giant cell reaction, neovascularization, and thermal changes of the vessel wall. CONCLUSIONS: The use of the ACE for PA branch sealing in VATS lobectomy is safe and effective in an animal survival model. Human studies are needed to determine the clinical safety of ultrasonic PA branch sealing before widespread clinical use.

Pulmonary Artery Sealing Using the HARMONIC ACE+ Shears for Video-Assisted Thoracoscopic Surgery Lobectomy.

BACKGROUND: The standard technique for pulmonary arterial (PA) branch sealing in video-assisted thoracoscopic surgery lobectomy consists of vascular endostaplers. We evaluated the immediate efficacy of an ultrasonic energy vessel-sealing device for sealing PA branches and compared it with the gold standard (endostapler) in an ex vivo model. METHODS: This was a prospective cohort study. Immediately after anatomical lung resection, PA vessel sealing was achieved using the HARMONIC ACE+ Shears (ACE; Ethicon, Cincinnati, OH) sealing device or a vascular endostapler (VES) in a 3:1 ratio based on vessel diameter. The vessel was slowly pressurized, and the bursting pressure was recorded. RESULTS: A total of 137 PA branches were sealed in specimens from 43 patients, of which 90 vessels were sealed with ACE and 47 were sealed with VES. The mean PA branch diameter was 6.0 mm (range, 1.7 mm to 24.0 mm; standard deviation, 3.1 mm Hg). The mean bursting pressure was 333.0 mm Hg (range, 84.0 mm Hg to 1415.1 mm Hg; standard deviation, 231.4 mm Hg) in the ACE group and 114.2 mm Hg (range, 0 mm Hg to 840.0 mm Hg; standard deviation, 124.7) in the VES group (p < 0.001). There were no complete sealing failures in the ACE group. Electron microscopy of ACE-sealed PA vessels demonstrated adventitial sealing with partial preservation of the collagen bundles and media with a sealed matrix of melted collagen. CONCLUSIONS: PA branches sealed using the HARMONIC ACE+ in a simulated ex vivo model were able to sustain high intraluminal pressures. ACE-sealed vessels burst at mean bursting pressures equal to or greater than the VES-stapled vessels.

Recurrence of a non-seminomatous germ cell tumor in the seminal vesicle 20 years after initial diagnosis and treatment.

We present a case of a pathologic stage 1, right sided, non-seminomatous germ cell tumor recurrence in the left seminal vesicle, 20 years after initial diagnosis and treatment. The patient was treated with three salvage cycles of bleomycin, etoposide, and cisplatinum. At 24 months of follow-up after completion of chemotherapy, digital rectal and TRUS examinations revealed complete resolution of the lesion. We believe that this tumor is a late metastasis to the contralateral seminal vesicle.

Endosonographic mediastinal lymph node staging of lung cancer.

BACKGROUND: It is unclear whether endoscopic mediastinal lymph node (LN) staging techniques are equivalent to surgical mediastinal staging (SMS) techniques in patients with potentially operable non-small cell lung cancer (NSCLC). METHODS: A total of 166 patients with confirmed or suspected NSCLC who required SMS based on current guidelines were enrolled in this prospective controlled trial comparing endosonographic mediastinal LN staging with SMS. Each patient served as his or her own control. All patients underwent endobronchial ultrasound (EBUS), endoscopic ultrasound (EUS), and SMS during a single procedure. Results of EBUS, EUS, and combined EBUS/EUS were compared with SMS (gold standard) and in patients with negative LN staging results, with LN sampling at pulmonary resection. RESULTS: EBUS, EUS, combined EBUS/EUS, and SMS sampled a mean of 2.2, 1.7, 3.9, and 3.1 LN stations, respectively. The prevalence of mediastinal nodal disease (N2/N3) was 32% (53 of 166 patients). The sensitivity, negative predictive value, and diagnostic accuracy of the endoscopic staging modalities, respectively, were EBUS, 72% (95% CI, 0.58-0.83), 88% (0.81-0.93), and 91% (0.85-0.95); EUS, 62% (0.48-0.75), 85% (0.78-0.91), and 88% (0.82-0.92); and combined EBUS/EUS, 91% (0.79-0.97), 96% (0.90-0.99), and 97% (0.93-0.99). Endosonography was diagnostic for N2/N3/M1 disease in 24 patients in whom SMS findings were negative, preventing futile thoracotomy in an additional 14% of patients. CONCLUSIONS: The combined EBUS/EUS procedure can replace surgical mediastinal staging in patients with potentially resectable NSCLC. Additionally, endosonography leads to improved staging compared with SMS because it allows the biopsy of LNs and metastases unattainable with SMS techniques. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01011595; URL: www.clinicaltrials.gov.

Episomal and integrated human papillomavirus type 16 loads and anal intraepithelial neoplasia in HIV-seropositive men.

OBJECTIVES: To assess levels of episomal and integrated human papillomavirus type 16 (HPV-16) loads in HIV-seropositive men who have sex with men (MSM) in anal infection and to study the association between episomal and integrated HPV-16 loads and anal intraepithelial neoplasia (AIN). STUDY DESIGN: A cohort study of 247 HIV-positive MSM followed each 6 months for 3 years. Overall, 135 (54.7%) men provided 665 HPV-16-positive anal samples. METHODS: Episomal and integrated HPV-16 loads were measured with quantitative real-time PCR assays. HPV-16 integration was confirmed in samples with a HPV-16 E6/E2 of 1.5 or more with PCR sequencing to demonstrate the presence of viral-cellular junctions. RESULTS: The HPV-16 DNA forms in anal samples were characterized as episomal only in 627 samples (94.3%), mixed in 22 samples (3.3%) and integrated only in nine samples (1.4%). HPV-16 episomal load [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.1], number of HPV types (OR = 1.4, 95% CI 1.1-1.8) and current smoking (OR = 4.8, 95% CI 1.3-18.6) were associated with high-grade AIN (AIN-2,3) after adjusting for age and CD4 cell counts. Integrated HPV-16 load was not associated with AIN-2,3 (OR = 0.7, 95% CI 0.4-1.1). Considering men with AIN-1 at baseline, four (16.7%) of the 24 men who progressed to AIN-2,3 had at least one sample with integrated HPV-16 DNA compared with three (23.1%) of 13 men who did not progress (OR = 0.7, 95% CI 0.2-3.8; P = 0.64). Integration was detected in similar proportions in samples from men without AIN, with AIN-1 or AIN-2,3. CONCLUSION: High episomal HPV-16 load but not HPV-16 integration load measured by real-time PCR was associated with AIN-2,3.

Genotyping of human papillomavirus DNA in anal biopsies and anal swabs collected from HIV-seropositive men with anal dysplasia.

BACKGROUND: Human papillomavirus (HPV) causes anal intraepithelial neoplasia (AIN) in HIV-seropositive men. The detection of HPV genotypes in anal biopsies and swabs was compared. METHODS: HPV DNA was detected in anal swabs and biopsies obtained concurrently from 154 HIV-seropositive men [31 without AIN, 60 low-grade AIN (AIN-1), 62 high-grade AIN (AIN-2,3), and 1 indeterminate AIN] under or eligible to highly active antiretroviral therapy. RESULTS: HPV DNA was detected in 24.2% of normal biopsies compared with 93.5% with AIN-2,3 (P < 0.001) and 88.3% with AIN-1 (P < 0.001). The proportion of biopsies containing multiple genotypes was greater in AIN-1 (n = 21, 35.0%; P = 0.002) and AIN-2,3 (n = 38, 58%; P < 0.001) than in normal biopsies (n = 2, 6.5%). The most frequent genotypes in order of frequency were in AIN-2,3 biopsies HPV-16, 18, 58, and 45 and were in AIN-1 biopsies HPV-6, 11, 16, and 39. Controlling for age, CD4 count, and smoking, the presence of high-risk HPV DNA in biopsies [odds ratio (OR) = 50.8, 95% confidence interval (CI): 13.0 to 199.5] but not in swabs (OR = 2.0, 95% CI: 0.6 to 7.0) was associated with AIN-2,3. CONCLUSIONS: AIN-2,3 was associated with high-risk HPV infection detected in biopsies but not in swabs in men under or starting highly active antiretroviral therapy, possibly due to the presence of HPV foci outside of the neoplastic lesion.