Oropharyngeal HPV Detection Techniques in HPV-associated Head and Neck Cancer Patients.

BACKGROUND/AIM: The incidence of human papilloma virus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has been increasing in the last decades. Analysis of oral brushing or rinsing samples for screening or stratification could potentially improve screening and prevention. PATIENTS AND METHODS: Oral brushes and mouthwashes were taken from 20 patients with HPV-associated HNSCC before definite therapy. HPV genotyping was performed for the detection of 14 high-risk HPV subtypes and correlated to DNA isolated from tumor tissue. RESULTS: Ten of 20 patients were tested HPV positive by using either method. There was a significant correlation between macroscopic visibility of tumor and positive HPV detection (p<0.001) and HPV detection and tumor size (p<0.001). HPV was detected in all macroscopically visible tumors. Half of the HPV cases who had macroscopically invisible tumors were missed by both methods. CONCLUSION: Both techniques are limited in the detection of macroscopically non-visible and small tumors. Therefore, the application of these techniques for screening or diagnosis of HNSCC is not recommended.

Indocyanine green fluorescence imaging during partial adrenalectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging represents an emerging technology that facilitates the assessment of tissue vascularity, tissue distinction, and tumor localization during surgery. The aim of this study was to investigate the potential role of ICG imaging during laparoscopic partial adrenalectomy. METHODS: Indocyanine fluorescence imaging was carried out during laparoscopic partial adrenalectomy for bilateral pheochromocytoma and bilateral Cushing's syndrome. A first bolus of 5 mg ICG was applied intravenously upon exposure of the retroperitoneal plane to identify the adrenal borders. The fluorescence was visualized using a Storz® NIR/ICG endoscopic system. As the camera of this system detects NIR light as a blue signal, the well-vascularized adrenal tissue was expected to show a strong fluorescence in the blue color channel in contrast to the surrounding adipose tissue. Following partial adrenalectomy, a second bolus of 5 mg ICG was applied intravenously to evaluate the vascularity of the remaining adrenal tissue. RESULTS: We investigated six adrenal glands from three patients undergoing bilateral partial adrenalectomy. The indication for surgery was pheochromocytoma in two patients and Cushing's syndrome with bilateral adenomas in one patient. Regarding left adrenalectomies, ICG imaging was helpful in visualizing the adrenal borders and the adrenal vein. Further, it facilitated the identification of the hypofluorescent pheochromocytoma and to resect the entire tumor. On the right side, due to the more apparent anatomy, ICG imaging did not contribute to the conduct of the operation. Four adrenal remnants showed a strong vascularization and two remnants were only reasonably vascularized. CONCLUSION: ICG fluorescence may be helpful in guiding partial adrenalectomy and assessing the vascularity of remaining adrenal tissue.

Intraoperative Near-Infrared Autofluorescence and Indocyanine Green Imaging to Identify Parathyroid Glands: A Comparison.

OBJECTIVE: To investigate the feasibility of near-infrared autofluorescence (AF) and indocyanine green (ICG) fluorescence to identify parathyroid glands intraoperatively. METHODS: Fluorescence imaging was carried out during open parathyroid and thyroid surgery. After visual identification, parathyroid glands were exposed to near-infrared (NIR) light with a wavelength between 690 and 770 nm. The camera of the Storz® NIR/ICG endoscopic system used detects NIR light as a blue signal. Therefore, parathyroid AF was expected to be displayed in the blue color channel in contrast to the surrounding tissue. Following AF imaging, a bolus of 5 mg ICG was applied intravenously. ICG fluorescence was detected using the same NIR/ICG imaging system. Well-vascularized parathyroid glands were expected to show a strong fluorescence in contrast to surrounding lymphatic and adipose tissue. RESULTS: We investigated 78 parathyroid glands from 50 patients. 64 parathyroid glands (82%) displayed AF showing the typical bluish violet color. 63 parathyroid glands (81%) showed a strong and persistent fluorescence after application of ICG. The sensitivity of identifying a parathyroid gland by AF was 82% (64 true positive and 14 false negative results), while ICG imaging showed a sensitivity of 81% (63 true positive and 15 false negative results). The Fisher exact test revealed no significant difference between both groups at p < 0.05. Neither lymph nodes nor adipose tissue revealed substantial AF or ICG fluorescence. CONCLUSION: AF and ICG fluorescence reveal a high degree of sensitivity in identifying parathyroid glands. Further, ICG imaging facilitates the assessment of parathyroid perfusion. However, in the current setting both techniques are not suitable as screening tools to identify parathyroid glands at an early stage of the operation.

Parathyroid Autofluorescence-How Does It Affect Parathyroid and Thyroid Surgery? A 5 Year Experience.

Injury to parathyroid glands during thyroid and parathyroid surgery is common and postoperative hypoparathyroidism represents a serious complication. Parathyroid glands possess a unique autofluorescence in the near-infrared spectrum which could be used for their identification and protection at an early stage of the operation. In the present study parathyroid autofluorescence was visualized intraoperatively using a standard Storz laparoscopic near-infrared/indocyanine green (NIR/ICG) imaging system with minor modifications to the xenon light source (filtered to emit 690 nm to 790 nm light, less than 1% in the red and green above 470 nm and no blue light). During exposure to NIR light parathyroid tissue was expected to show autofluorescence at 820 nm, captured in the blue channel of the camera. Over a period of 5 years, we investigated 205 parathyroid glands from 117 patients. 179 (87.3%) glands were correctly identified by their autofluorescence. Surrounding structures such as thyroid, lymph nodes, muscle, or adipose tissue did not reveal substantial autofluorescence. We conclude that parathyroid glands can be identified by their unique autofluorescence at an early stage of the operation. This may help to preserve these fragile structures and their vascularization and lower the rate of postoperative hypocalcemia.

Intraoperative near-infrared autofluorescence imaging of parathyroid glands.

OBJECTIVE: To identify parathyroid glands intraoperatively by exposing their autofluorescence using near-infrared light. METHODS: Fluorescence imaging was carried out during minimally invasive and open parathyroid and thyroid surgery. After identification, the parathyroid glands as well as the surrounding tissue were exposed to near-infrared (NIR) light with a wavelength of 690-770 nm using a modified Karl Storz near-infrared/indocyanine green (NIR/ICG) endoscopic system. Parathyroid tissue was expected to show near-infrared autofluorescence, captured in the blue channel of the camera. Whenever possible the visual identification of parathyroid tissue was confirmed histologically. RESULTS: In preliminary investigations, using the original NIR/ICG endoscopic system we noticed considerable interference of light in the blue channel overlying the autofluorescence. Therefore, we modified the light source by interposing additional filters. In a second series, we investigated 35 parathyroid glands from 25 patients. Twenty-seven glands were identified correctly based on NIR autofluorescence. Regarding the extent of autofluorescence, there were no noticeable differences between parathyroid adenomas, hyperplasia and normal parathyroid glands. In contrast, thyroid tissue, lymph nodes and adipose tissue revealed no substantial autofluorescence. CONCLUSION: Parathyroid tissue is characterized by showing autofluorescence in the near-infrared spectrum. This effect can be used to distinguish parathyroid glands from other cervical tissue entities.

Laparoscopic adrenalectomy--10-year experience at a teaching hospital.

BACKGROUND: Minimally invasive adrenalectomy has been adopted as the treatment of choice for benign adrenal tumors. This study aimed to investigate the outcome of laparoscopic adrenalectomies performed over a 10-year period at a teaching hospital. METHODS: All laparoscopic adrenalectomies carried out between 1 April 2000 and 31 March 2010 were evaluated with respect to perioperative management, complications, conversion rate, learning curve, tumor size, and surgically relevant characteristics of different adrenal pathologies. RESULTS: Over a period of 10 years, 215 laparoscopic lateral transabdominal adrenalectomies were carried out for Conn's syndrome (n = 90), Cushing's syndrome (n = 72), pheochromocytoma (n = 30), metastatic disease (n = 8), incidentalomas (n = 10), and other rare adrenal pathologies (n = 5). Morbidity, mortality, and conversion rate were 7.0, 0.9, and 4.2 %, respectively. Patients with Cushing's disease and bilateral adrenalectomy showed a higher complication rate. In retrospect, the indication for a laparoscopic approach was at least questionable in five cases. During these 10 years, four surgeons unfamiliar with the technique received intensive training to a defined plan. CONCLUSIONS: Laparoscopic adrenalectomy represents a safe operating technique associated with few complications and a low conversion rate. Patients with severe Cushing's disease are prone to complications and require intensive monitoring postoperatively. Laparoscopic adrenalectomy is associated with a learning curve, and particular emphasis should be given to surgical training.

Intraoperative optical coherence tomography imaging to identify parathyroid glands.

OBJECTIVE: Optical coherence tomography (OCT) is a non-invasive high-resolution imaging technique that permits characterization of microarchitectural features in real time. Previous ex vivo studies have shown that the technique is capable of distinguishing between parathyroid tissue, thyroid tissue, lymph nodes, and adipose tissue. The purpose of this study was to evaluate the practicality of OCT during open and minimally invasive parathyroid and thyroid surgery. METHODS: During parathyroid and thyroid surgery, OCT images were generated from parathyroid glands, thyroid tissue, lymph nodes, and adipose tissue. The images were immediately assessed by the operating team using the previously defined criteria. Second, the OCT images were blinded with respect to their origin and analyzed by two investigators. Whenever possible the OCT findings were matched to the corresponding histology. RESULTS: A total of 227 OCT images from 27 patients undergoing open or minimally invasive thyroid or parathyroid surgery were analyzed. Parathyroid glands were correctly identified in 69.2%, thyroid tissue in 74.5%, lymph nodes in 37.5%, and adipose tissue in 69.2%. 43 OCT images (18.9%) could not be allocated to one of the tissue types (Table 2). Sensitivity and specificity in distinguishing parathyroid tissue from the other entities were 69% (63 true positive, 13 false negative findings, 15 images where an allocation was not possible) and 66%, respectively (71 true negative, 9 false positive, 28 images where an assessment was not possible). CONCLUSION: OCT is capable of distinguishing between parathyroid, thyroid, and adipose tissue. An accurate differentiation between parathyroid tissue and lymph nodes was not possible. The disappointing results compared to the previous ex vivo study are related to problems handling the endoscopic probe intraoperatively. However, further refinement of this new technology may lead to OCT systems with higher resolution and intraoperative probes that are easier to handle.

Optical coherence tomography as a method to identify parathyroid glands.

BACKGROUND AND OBJECTIVE: The identification of parathyroid glands can be a major problem in parathyroid surgery. The purpose of this study was to evaluate the feasibility of optical coherence tomography (OCT) in distinguishing between parathyroid tissue, thyroid tissue, lymph nodes, and adipose tissue. METHODS: Ex vivo OCT images as well as histological sections were generated from parathyroid glands, thyroid tissue, lymph nodes and fat in order to define significant morphologic differences between these entities. As a second step all OCT images were separately evaluated by two blinded investigators and later compared to the corresponding histology. Sensitivity and specificity of OCT in distinguishing between the different tissues were determined. To assess the interobserver agreement, κ coefficients were calculated from the ratings of each investigator for each OCT image seen. RESULTS: A total of 320 OCT images from 32 patients undergoing thyroid surgery, parathyroidectomy or lymphadenectomy were compared with the corresponding histology. The sensitivity and specificity in distinguishing parathyroid tissue from the other entities was 84% (second investigator: 82%) and 94% (93%) respectively. Unweighted κ using four diagnostic categories was 0.97 (95% CI, 0.94-0.99) showing substantial agreement between both investigators. CONCLUSION: OCT is highly sensitive in distinguishing between parathyroid tissue, thyroid tissue, lymph nodes and adipose tissue. These ex vivo results should be confirmed by using OCT imaging intraoperatively.

Optical coherence tomography for the diagnosis of cervical intraepithelial neoplasia.

BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) permits high-resolution imaging of tissue subsurfaces up to 2 mm in depth. The purpose of this study was to evaluate the accuracy and reproducibility of OCT in the characterization of cervical intraepithelial neoplasia (CIN) and to distinguish between different CIN grades. STUDY DESIGN/MATERIALS AND METHODS: Colposcopy-guided OCT images were taken from unsuspicious and suspicious areas in women with suspected CIN. Each woman then underwent directed biopsies. All OCT images were separately evaluated by two blinded investigators and later compared to the corresponding histology based on a 6-grade classification (normal, inflammation, CIN 1, CIN 2, CIN 3, squamous carcinoma). Sensitivity and specificity of OCT in detecting CIN were determined. To assess the interobserver agreement, kappa coefficients were calculated from the ratings of each investigator for each OCT image seen. RESULTS: A total of 210 OCT images were compared with the corresponding histology in 120 women undergoing colposcopy for suspected CIN. Sensitivity calculated for both investigators was 98% and 96% respectively with the threshold at CIN1 and 86% and 84% respectively with the threshold at CIN2. Thirty nine (38) false positive results reduced the specificity to 39% and 41% respectively with the threshold at CIN1. Defining the threshold at CIN2 the specificity increased to 64% and 60% respectively. Unweighted kappa from a dichotomous classification with the threshold at CIN1 was 0.69 (95% CI, 0.54-0.84) and 0.62 (95% CI, 0.51-0.73) with the threshold at CIN2. CONCLUSION: OCT is highly sensitive in identifying pre-invasive and invasive cancer of the uterine cervix. Improvements in resolution and the development of new light sources and optics may improve the specificity as well as the differentiation of cervical dysplasia. The interobserver agreement was substantial.