Transoral thyroid surgery vestibular approach.

Objectives: Transoral thyroid surgery vestibular approach (TOETVA) is a novel and feasible surgical technique that allows for cervical surgery without visible incisions. TOETVA represents a new frontier in endocrine surgery since aesthetic results play a more and more decisive role in elective surgery. However, acceptance is different around the world with widespread prevalence in Asian countries and some high-volume centres in the US. While inclusion criteria for TOETVA are limited regarding size and volume a combination with other extracervical techniques like the retroauricular endoscopic cephalic access thyroid surgery (EndoCATS) approach or transaxillary access is an option. Methods: TOETVA is carried out through a three-port technique placed at the oral vestibule. Originally one 10-mm port for a 30° endoscope and two additional 5-mm ports for dissecting and coagulating instruments are used. Alternatively, one 5-mm and one or two 3 mm ports can be used. CO2 insufflation pressure is set at 6 mmHg. An additional device to optimize gas outflow for optimum view might be helpful. An anterior cervical subplatysmal space is created by hydrodissection from the oral vestibule to the sternal notch, laterally to the sternocleidomastoid muscle. Conventional endoscopic instruments are used. Combination of TOETVA with a modified retroauricular access includes insertion of a 10-12 mm trocar placed subcutaneously via a skin incision on the scalp, behind the ear by blunt dissection. Results: Since Anuwong published the first case series of 60 patients who underwent scarless thyroidectomy via the lower vestibule of the mouth with excellent results in 2016 almost 1,000 cases are reported in literature to date with comparable results especially regarding traditional complications. In contrast to other extracervical approaches, areolar or axillary for example, the transoral access route is short and the dissection planes are rather like transcervical surgery. Surgical indications and contraindications have been modified since its first description and are partly institution specific to date. To amend indications combination with other extracervical techniques is an option. In addition, patients must carefully be selected for and surgeons` candidacy is of utmost importance in transoral surgery. Conclusions: Transoral surgery will likely continue to gain attraction as surgeons become more experienced with the technique. With increased operative use and surgeon experience the gap in conventional outcomes between transoral surgery and the transcervical approach will narrow, with both operative time and the incidence of specific complications diminishing. Experience in thyroid and endoscopic surgery is required to achieve excellent results with low complication rates. However, the new transoral technique is related to novel complications that must be evaluated.

Flexible single port access in transoral endoscopic thyroidectomy vestibular approach.

Background: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is regarded the only no-scar technique which combines minimized surgical trauma with all advantages of endoscopy such as enhanced view, fluorescent parathyroid imaging (FPI) and optimum cosmesis. Addressing TOETVA specific local risk profiles like mental nerve injury, the potential of skin lesions or difficult specimen retrieval we modified the three trocar based TOETVA towards a soft single port platform. Methods: Single port-TOETVA (SP-TOETVA) was established and retrospectively analysed in five patients using a soft handmade single port housing multiple trocar valves. Standard laparoscopic instruments, one articulating instrument and a vessel-sealing device were utilized. CO2 insufflation was maintained at 6-8 mmHg. Results: In all patients SP-TOETVA was completed successfully. Hemigland and total thyroid volumes ranged from 5-40 and 55 mL, respectively. Neither additional trocars nor conversion to open was required. Operation time yielded 102-214 min. Neuromonitoring and FPI were applied. The soft wound protection foil served for convenient specimen harvest. No intra- or postoperative complication occurred. In particular, no functional impairment on mental nerve was seen. Conclusions: SP-TOETVA with the soft and flexible handmade single port system is feasible and ensures wound protection. It allows for easy instrument application and benefits of minimally invasive surgery without the specific risk of lateral vestibular incisions.

Transoral thyroid surgery vestibular approach: is there an increased risk of surgical site infections?

Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is an upcoming surgical technique with the aim to optimize cosmetic outcome avoiding visible scars in the neck. However, the transoral access bears the risk of contamination and microbial allocation from the mouth into the thyroid region. Therefore, some authors recommend extended antibiotic therapy up to 7 days after surgery. Our aim was to evaluate infection rates and parameters before and after transoral surgery and to suggest a viable and safe routine in transoral surgery. Prospectively collected data of patients who were eligible for transoral surgery in Austria and Germany between June 2017 and July 2020 were retrospectively evaluated focussing on clinical and laboratory infection signs pre and postoperatively. White blood cell count (WBC) and C-reactive protein levels (CRP) were estimated before and after surgery. Patients` characteristics, surgical outcome and complications were also determined and compared to the current results reported in the literature. 113 transoral operations were performed in 108 patients. In 37 of 108 (36%) patients an additional retroauricular incision in the hairline and in two patients a submental skin incision was performed to extract thyroid specimen of more than 40 ml. Intravenous antibiotic prophylaxis and enoral mucosal disinfection were used in all patients before surgery. WBC and CRP levels were available in 75 patients. Median WBC was 5800/µl (range 3500-10,500/µl) before and significantly higher (median 8900/µl, range 4500-18,800 µl; p < 0.01) at day one after surgery. WBC returned to normal range (4500-11,500/µl) in all patients within the first 7 days postoperatively (median 5300/µl, range 3400-8700/µl). CRP levels were normal before (< 0.5 mg/dl) and slightly elevated within the first two days after surgery (Median 2.0 mg/dl, range 0.5-6.4 mg/dl, n.s.). In one patient oral antibiotic therapy was necessary due to transient erythema in the chin region which occurred 10 days after surgery and resolved completely without surgical intervention. Despite a transient increase in WBC transoral thyroid and parathyroid surgery via the vestibular approach does not seem to be associated with a significant number of wound infections in our patients. Intravenous antibiotic prophylaxis and enoral mucosal disinfection might be reasonable procedures to avoid microbial allocation from the mouth into the thyroid region. However, further investigations are required to finally estimate the need of antibiotics in transoral surgery.

Influence of Parathyroidectomy on Bone Metabolism and Bone Pain in Patients with Secondary Hyperparathyroidism.

BACKGROUND: After parathyroidectomy (PTX), hungry bone syndrome leads to hypocalcemia due to bone remineralization. The aim of this pilot study was to analyze changes in markers of bone metabolism in patients with secondary hyperparathyroidism (sHPT) after PTX and to correlate these markers with bone pain measured with a validated questionnaire. MATERIALS AND METHODS: All patients who underwent PTX for sHPT between March 2010 and February 2012 at out institution were included in this prospective observational pilot study. At the day before surgery and on the 3rd day thereafter, levels of parathyroid hormone (PTH), calcium, osteocalcin, alkaline phosphatase (AP), bone-specific AP (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), osteoprotegerin (OPG), sclerostin, fibroblast growth factor 23, and Klotho were measured. Additionally, all patients were requested to answer the Brief Pain Inventory preoperatively and on the 5th postoperative day. RESULTS: A total of 35 patients with a mean age of 49.8 years were analyzed. A significant difference between the pre- and postoperative values could be detected in PTH, calcium, BAP, TRAP5b, and sclerostin. The highest correlation of laboratory markers with bone pain was found for preoperative PTH (r = 0.3), postoperative OPG (r = 0.4), postoperative BAP (r = -0.4), and postoperative Klotho (r = -0.4). CONCLUSIONS: The present study revealed significant perioperative changes in PTH, BAP, sclerostin, and TRAP5b after PTX. These markers may serve as laboratory markers to monitor bone metabolism in patients with sHPT. PTH, OPG, and sclerostin were the parameters with the closest correlation to bone pain. However, larger prospective trials with a longer follow-up are required to confirm these results.

Immunohistochemical Expression of E-Cadherin in Atypical Parathyroid Adenoma.

BACKGROUND: Atypical parathyroid adenoma (APA) is a rare entity, sharing clinical symptoms like solid palpable mass in the neck, laboratory changes with very high serum calcium and parathyroid hormone levels, and some histopathological features with parathyroid carcinomas (PC). However, clinical behavior of APA seems to comply with benign parathyroid tumors (PA). There is some evidence that loss of the membranous staining pattern of E-Cadherin (E-Cad) suggests a key role of epithelial mesenchymal transition in the tumorigenesis of PC. Thus, the aim of this study was to compare clinical and surgical characteristics and immunohistochemical expression of E-Cad in APA, PC, and PA. METHODS: Data of patients who underwent surgery for primary hyperparathyroidism (pHPT) between 1985 and 2010 were retrospectively evaluated. All data were analyzed with special regard to distinctive criteria of APA, including trabecular growth, broad fibrous bands, nuclear atypia, mitosis, pseudocapsular invasion or strong adherence to the surrounding tissue, and potential invasive growth of a grossly altered and enlarged parathyroid gland. In addition, laboratory and clinical data were evaluated and additional immunohistochemical staining with E-Cad was performed in suspicious APA patients with available tissue. RESULTS: In 68 patients (39 female, 29 male), the parathyroid tumor was suspicious for APA. In 46 patients, a bilateral cervical exploration was performed. 15 patients underwent an en bloc resection including a hemithyroidectomy and lymphonodular dissection of the ipsilateral central compartment due to the malignant macroscopic aspect of the parathyroid. In seven patients, a focused parathyroid resection was done. The available parathyroid tissue of 38 APA patients was immunopositive for membranous E-Cad staining. During follow-up, only one patient with a successful initial surgery suffered from recurrent pHPT due to another solitary PA 10 years after initial surgery but without evidence of malignancy. CONCLUSIONS: In contrast to PC, parathyroid tumors suspicious for APA are characterized by a strong membranous E-Cad staining and, like PA, by a benign clinical course.

Transoral parathyroid surgery--a new alternative or nonsense?

PURPOSE: In recent years, several endoscopic techniques have been explored in thyroid and parathyroid surgery, but only few gained acceptance among patients and surgeons. Based on extensive human cadaver and animal studies, we developed a technique for transoral partial parathyroidectomy (TOPP), which was performed for the first time in a patient with primary hyperparathyroidism (pHPT). We now report on results and the acceptance of this new technique 2 years after its implementation. METHODS: A pilot study was initiated to recruit a total of 10 patients with benign sporadic pHPT and a preoperatively localized parathyroid adenoma eligible for initial parathyroidectomy. The study protocol was approved by the ethics committee, and an insurance for unforeseen complications and risks was procured. Data of all patients evaluated and operated were prospectively collected, and follow-up examinations were carried out for 19 months on average, which included clinical examinations; ultrasonography; Ear, Nose, and Throat (ENT) investigations; and blood testing. RESULTS: Between January 2010 and May 2012, 75 patients with pHPT and a preoperative localized parathyroid adenoma were eligible for TOPP. After detailed information about the transoral procedure, only five (7 %) female patients consent to undergo TOPP. In three patients, a parathyroid adenoma could be removed via the transoral access, In two patients, the procedure had to be converted to the conventional technique. Median time until resection of a parathyroid adenoma was 122 min (range, 45-175). One patient had a transient recurrent laryngeal nerve palsy, while one patient suffered from a transient palsy of the right hypoglossal nerve and a slight but persisting dysgeusia. Three patients developed a hematoma of the mouth floor and swallowing problems. In four patients, the visual analog scale (VAS) pain score was high (>7) within the first 2 postoperative days. CONCLUSIONS: Although TOPP is feasible, it is poorly accepted by patients and its complication rate is high. Thus, TOPP is nonsense with currently available devices.

Initial surgery for benign primary hyperparathyroidism: an analysis of 1,300 patients in a teaching hospital.

BACKGROUND: Success rates of initial surgery for primary hyperparathyroidism (pHPT) are greater than 95 % in specialized centers, mostly referring to single-surgeon experiences. The present study was performed to identify changes in clinical manifestations, diagnostic procedures, surgical strategies, and outcome of initial parathyroid interventions in a teaching hospital during the past 25 years with special regard to the surgical expertise. METHODS: Clinical data of patients who underwent an initial neck exploration for benign pHPT between 1985 and 2010 at the University hospital Marburg were retrospectively evaluated. All data were analyzed particularly with regard to the implementation of additional pre- and intraoperative procedures and to the particular surgical strategy. In addition, operative results were furthermore analyzed with regard to the experience of the responsible surgeons. RESULTS: An initial neck exploration for benign pHPT was performed in 1,300 patients. Of these, 1,035 patients had a bilateral cervical exploration (BCE) and 265 patients had a focused, minimally invasive parathyroidectomy (MIP). Cure rates did not differ between focused surgeries and BCE (98.9 vs. 98.3%, p = 0.596) after a mean follow-up of 33.4 (± 44.3) months. Postoperative transient hypoparathyroidism was significantly lower in the MIP group (11 vs. 47%, p < 0.0001). The rate of permanent recurrent laryngeal nerve palsies (0.4 vs. 2%, p = 0.064) and nonsurgical complications (0 vs. 1.4%, p = 0.0875) tended to be lower in the MIP group. Success and complication rates of chief surgeons (n = 2), attending surgeons (n = 20), and residents (56 < 3 years, 30 > 3 years) were similar, despite a significantly shorter operating time in the chief surgeon group (p < 0.01). CONCLUSIONS: Despite the implementation of several diagnostic procedures and significant changes concerning the surgical strategy, high success rates of primary interventions for pHPT did not change over the past three decades. High success rates also can be achieved in a teaching hospital, provided that surgery is supervised by an experienced endocrine surgeon. MIP is the treatment of choice in patients with benign sporadic pHPT and positive preoperative localization studies.

The influence of parathyroidectomy on restless legs syndrome in patients with renal hyperparathyroidism.

BACKGROUND: Restless legs syndrome (RLS) is a common and poorly understood movement disorder that leads to unpleasant leg sensations. Although RLS can be idiopathic, secondary etiologies such as iron deficiency and renal failure are common. The aim of this prospective cohort study was to evaluate whether RLS is a common feature in patients undergoing parathyroidectomy for renal hyperparathyroidism (rHPT) and if RLS-related symptoms can be influenced by surgery. METHODS: After providing written consent, patients who underwent a parathyroidectomy for rHPT between January and November 2011 answered a validated RLS-screening-questionnaire (RLSSQ). If this was suggestive for RLS a confirming questionnaire (IRLS) was also completed on the day before surgery, on the fifth postoperative day, and again during follow-up (minimum 12 months). Perioperative parathyroid hormone and calcium levels, as well as the scores of the questionnaires were analyzed. RESULTS: Twenty-one patients (14 men, 7 women) with a mean age of 47.8 ± 3.2 years underwent total parathyroidectomy with bilateral cervical thymectomy and parathyroid autotransplantation for rHPT. The mean score of the RLSSQ of all 21 patients prior to operation was 6.1 ± 0.5. In 10 of 21 patients (47.6 %) the results of the RLSSQ were suggestive for RLS with a mean score of 8.0 ± 0.3. The consecutive scores of the IRLS in these latter patients significantly dropped from 26.6 ± 1.4 to 19.0 ± 2.2 between the preoperative and postoperative settings (p < 0.05). After a mean follow-up of 17.3 ± 3.7 months the mean scores of the RLSSQ and the IRLS were 6.1 ± 0.6 and 16.3 ± 1.8. CONCLUSIONS: rHPT may play a major role in the severity of RLS-associated symptoms in patients with renal failure. Consequently, parathyroidectomy may prove to be a valuable tool to reduce RLS-associated morbidity in affected patients. However, larger prospective trials are required to confirm the possible relation between RLS and rHPT seen in the present study

Reoperations for primary hyperparathyroidism--improvement of outcome over two decades.

PURPOSE: Reoperations (R-PTX) for primary hyperparathyroidism (pHPT) are challenging, since they are associated with increased failure and morbidity rates. The aim was to evaluate the results of reoperations over two decades, the latter considering the implementation of Tc(99m)sestamibi-SPECT (Mibi/SPECT), intraoperative parathormone (IOPTH) measurement, and intraoperative neuromonitoring (IONM). PATIENTS AND METHODS: Data of 1,363 patients who underwent surgery for pHPT were retrospectively analyzed regarding reoperations. Causes of persistent (p) pHPT or recurrent (r) pHPT, preoperative imaging studies, surgical findings, and outcome were analyzed. Data of patients who underwent surgery between 1987 and 1997 (group 1; G1) and between 1998 and 2008 (group 2; G2) with the use of Mibi/SPECT, IOPTH, and IONM were evaluated. RESULTS: One hundred twenty-five patients with benign ppHPT (n = 108) or rpHPT (n = 17) underwent reoperations (R-PTX). Group 1 included 54, group 2 71 patients. Main cause of ppHPT (G1 = 65 % vs. G2 = 53 %) and rpHPT (G1 = 80 % vs. G2 = 60 %) was the failed detection of a solitary adenoma (p = 0.2). Group 1 patients had significantly less unilateral/focused neck re-explorations (G1 = 23 % vs. G2 = 57 %, p = 0.0001), and more sternotomies (G1 = 35 vs. G2 = 14 %, p = 0.01). After a median follow-up of 4 (range 0.9-23.4) years, reversal of hypercalcemia was achieved in 91 % (G1) and in 98.6 % in group 2 (p = 0.08, OR 7.14 [0.809-63.1]). The rates of permanent recurrent laryngeal nerve palsy (G1 = G2 = 9 %, p = 1) and of postoperative permanent hypoparathyroidism (G1 = 9 % vs. G2 = 6 %, p = 0.5) were not significantly different. Other complications such as wound infection, postoperative bleeding, and pneumonia were significantly lower in group 2 (p < 0.001). CONCLUSION: Nowadays, cure rates of R-PTX are nearly the same as in primary operations for pHPT. These results can be achieved in high-volume centers by routine use of well-established preoperative Mibi/SPECT and US in combination with IOPTH. However, morbidity is still considerably high.

Does contrast-enhanced cervical ultrasonography improve preoperative localization results in patients with sporadic primary hyperparathyroidism?

OBJECTIVE: Pre-operative localization studies are inevitable in patients with primary hyperparathyroidism (pHPT), who are eligible for focused or minimally invasive parathyroidectomy (MIP). High-resolution ultrasonography (US) in combination with planar (99m)Tc-Sestamibi-scintigraphy (MIBI) and additional single-photon emission computed tomography (SPECT) are the standard procedures to localize enlarged parathyroid glands. Our aim was to evaluate the practicability and significance of contrast-enhanced ultrasonography (CEUS) in patients with pHPT. MATERIALS AND METHODS: All investigations were performed at the University Hospital Marburg. Totally, 25 patients with biochemical proven pHPT underwent preoperative US, MIBI/SPECT, and CEUS. For CEUS, a suspension of phospholipid-stabilized sulfur-hexafluoride (SF6) microbubbles in combination with a special 12 MHz linear US probe was used. All patients were investigated by two sonographers, who did not get to view the findings noted by the other. Finally, surgery was performed and histopathological results were obtained from 24 patients. RESULTS: In 17 (68%) patients, US and MIBI/SPECT already raised suspicion of parathyroid lesions and all suspected lesions were reassessed by CEUS. However, no additional information was obtained using CEUS. Especially in eight patients with negative or inconsistent US and MIBI/SPECT results, CEUS did not provide additional information regarding the site of the suspected parathyroid adenoma. Overall, no side effects were observed using CEUS. Surgical cure was achieved in all patients. CONCLUSION: In this limited cohort of patients, no additional information could be obtained using the costly CEUS compared to results of US and MIBI/SPECT.

Development of a formula to predict parathyroid carcinoma in patients with primary hyperparathyroidism.

BACKGROUND: Cure of parathyroid carcinoma (PC) requires initial en bloc resection, including resection of all tumor-bearing tissue, with hemithyroidectomy and dissection of the central lymph node compartment. Unfortunately, no reliable preoperative criteria have yet been assessed to indicate a high likelihood of PC. Thus, the aim of the present study was to develop a formula to indicate preoperatively the presence of PC. METHODS: A prospective database of 1,363 patients with primary hyperparathyroidism (pHPT) was screened for patients with PC. Age, gender, surgical procedures, laboratory data, and follow-up results were evaluated and compared to a group of patients with benign pHPT. Based on preoperative serum calcium (Ca) and parathyroid hormone (PTH) levels, as well as patients' age at the time of diagnosis, a formula was developed by a multivariate logistic model that estimates the individual risk for PC. RESULTS: Between 1987 and 2008, 19 patients with PC were identified. Ca (3.8 ± 0.3 vs 2.9 ± 0.3 mmo/l; p = 0.0002) and PTH levels (1,250 ± 769 vs 194 ± 204 pg/ml; p = 0.0030) were significantly higher in patients with PC than in those with benign pHPT. Patients with PC were also significantly younger than patients with benign pHPT (48.9 ± 12.1 vs 59.1 ± 13.8 years; p < 0.05). With a ≥5 % probability that a given patient suffered from PC, the sensitivity and specificity to identify the disease were 100 and 30 %, respectively, with the new Ca, PTH, and age based logarithmic formula. CONCLUSIONS: The new logarithmic formula can be used to calculate the individual risk for PC. If the calculated individual risk exceeds 5 %, en bloc resection seems to be justified to provide long-term cure in case of PC.

Classification of parathyroid cancer.

PURPOSE: Parathyroid cancer is rare and often has a poor outcome. There is no classification system that permits prediction of outcome in patients with parathyroid cancer. This study was designed to validate two prognostic classification systems developed by Talat and Schulte in 2010 ("Clinical Presentation, Staging and Long-term Evolution of Parathyroid Cancer," Ann Surg Oncol 2010;17:2156-74) derived from a retrospective literature review of 330 patients. METHODS: This study contains 82 formerly unreported patients with parathyroid cancer. Death due to disease was the primary end point, and recurrence and disease-free survival were the secondary end points. Data acquisition used a questionnaire of predefined criteria. Low risk was defined by capsular and soft tissue invasion alone; high risk was defined by vascular or organ invasion, and/or lymph node or distant metastasis. A differentiated classification system further classified high-risk cancer into vascular invasion alone (class II), lymph node metastasis or organ invasion (class III), and distant metastasis (class IV). Statistical analyses included risk analysis, Kaplan-Meier analysis, and receiver-operating characteristic (ROC) analysis. RESULTS: Follow-up ranged 2-347 months (mean 76 months). Mortality was exclusive to the high- risk group, which also predicted a significant risk of recurrence (risk ratio 9.6; 95% confidence interval 2.4-38.4; P < 0.0001), with significantly lower 5-year disease-free survival (χ(2) = 8.7; P < 0.005 for n = 45). The differentiated classification also provided a good prognostic model with an area under the ROC curve of 0.83 in ROC analysis, with significant impairment of survival between classes (98.6%, 79.2%, 71.4%, 40.0%, P < 0.05 between each class). CONCLUSIONS: This study confirms the validity of both classification systems for disease outcome in patients with parathyroid cancer.

Initial parathyroid surgery in 606 patients with renal hyperparathyroidism.

BACKGROUND: The aim of the present study was to evaluate the outcome of different surgical procedures for patients on permanent dialysis who underwent initial parathyroidectomy for renal hyperparathyroidism (rHPT). METHODS: Out of a prospective database of patients who underwent parathyroid surgery for rHPT between 1976 and 2009, patients on permanent dialysis who underwent initial parathyroidectomy were further analyzed regarding perioperative biochemical changes and postoperative outcome. RESULTS: A total of 606 patients were analyzed. Total parathyroidectomy with autotransplantation (group A) was performed in 504 patients, total parathyroidectomy without autotransplantation in 32 (group B), subtotal parathyroidectomy in 21 (group C), and incomplete parathyroidectomy in 49 (group D). After surgery, mean calcium levels dropped from 2.76 to 1.91 mmol/l in group A, from 2.67 to 2.11 mmol/l in group B, from 2.70 to 2.09 mmol/l in group C, and from 2.65 to 1.94 mmol/l in group D. The parathyroid hormone level dropped from 1,371.4 pg/ml to 28.8 pg/ml in group A, from 1,078.4 pg/ml to 27.0 pg/ml in group B, from 2,377.9 pg/ml to 61.4 pg/ml in group C, and from 1,010.2 pg/ml to 99.5 pg/ml in group D. Persistent rHPT occurred in 2/504 patients from group A (0.4%), 0/32 patients from group B (0%), 1/21 patients from group C (4.8%), and 2/49 patients from group D (4.1%). After a mean follow-up of 57.6 months, recurrent rHPT occurred in 27/504 patients from group A (5.4%), in 0/32 patients from group B (0%), in 2/21 patients from group C (9.5%), and in 3/49 patients from group D (6.1%). CONCLUSIONS: Total parathyroidectomy with or without autotransplantation is a feasible and safe surgical procedure for patients on permanent dialysis with otherwise uncontrollable rHPT.

Transoral thyroid and parathyroid surgery--development of a new transoral technique.

BACKGROUND: Transluminal interventions via so-called natural orifices are gaining interest because they allow operative treatment without any skin incision. We previously described a transoral access for (para-)thyroid resection in pigs. To proceed with the first clinical trials, we evaluated the safety of the new technique. METHODS: Transoral hemithyroidectomies were performed on 10 living pigs using a special cervicoscope and conventional laparoscopic instruments. Follow-up examinations were carried out for 14 days and followed by autopsy, which included macroscopic evaluation, microbiologic investigations, and blood testing. In addition, refinement of the new technique was achieved by developing the techniques in 10 human cadavers. Finally, transoral parathyroidectomies were performed in 2 patients with primary hyperparathyroidism and a preoperatively localized parathyroid adenoma. RESULTS: All animal transoral hemithyroidectomies were performed without complications. Postoperatively, oral intake, weight gain, and white blood cell count remained normal. At autopsy, the access route, and operative field showed no signs of infection, and microbiologic swabs remained sterile. Based on these results, a transoral parathyroidectomy was performed successfully in 2 female patients with primary hyperparathyroidism; 1 patient experienced a transient palsy of the right hypoglossal nerve. CONCLUSION: Transoral parathyroid and thyroid operation is feasible; however, additional controlled clinical studies are required to evaluate the safety and success rates of this new technique.

Transoral thyroid and parathyroid surgery.

BACKGROUND: Translumenal endoscopic interventions via so-called natural orifices are gaining increasing interest because they allow surgical treatment without any incision of the skin. Moreover, minimally invasive procedures have found their way into thyroid and parathyroid surgery. Our goal was to develop a new access for thyroid and parathyroid resection via an entirely transoral approach. METHODS: We managed to find an entirely transoral sublingual access to the thyroid region in pigs and human cadavers. Using a modified rigid rectoscope (oraloscope) hemithyroidectomies as well as resection of parathyroid glands were performed via this new approach. Preparation and resection was performed using conventional laparoscopic instruments. In living pigs, integrity of the recurrent laryngeal nerve after resection could be documented by neuromonitoring. An absorbable suture was used to seal the mucosal incision. RESULTS: First, hemithyroidectomy was performed via the transoral access in 10 porcine cadavers, then in 10 living and orally intubated pigs, and finally in five human corpses. In humans, resection of parathyroid glands also was performed. We gained access to the thyroid region by blunt dissection of the layer behind the hyoid bone and the strap muscles of the neck. We did not observe any complication during the insertion, resection, and removal part of the new procedure. CONCLUSIONS: Entirely transoral thyroid and parathyroid surgery via sublingual access seems to be feasible. However, further investigations are needed to evaluate the safety of the new technique, especially potential and clinically relevant contamination of the access route has to be excluded.

Unique expression pattern of the EMT markers Snail, Twist and E-cadherin in benign and malignant parathyroid neoplasia.

BACKGROUND: Epithelial and mesenchymal transitions (EMT) are essential for embryonic development and progression of non-invasive tumor cells into malignant, metastatic carcinomas. During embryogenesis, the parathyroid glands develop from pharyngeal pouches and migrate to their final destinations, densely enclosed by mesenchymal neural crest cells. In this study, we examined the expression of the EMT markers Snail, Twist and E-cadherin in normal parathyroid glands and benign and malignant parathyroid diseases. METHODS: Using immunohistochemistry, we compared expression of E-cadherin, Snail and Twist in 25 patients with parathyroid adenoma, 25 patients with parathyroid hyperplasia, and nine patients with parathyroid cancer with normal parathyroid glands. RESULTS: Normal parathyroid glands, parathyroid adenomas, and parathyroid hyperplasias showed a typical membranous E-cadherin staining pattern. Expression of Snail was found in 22/25 parathyroid adenomas and in all parathyroid hyperplasias. Twist was expressed in 22/25 of parathyroid adenomas and in 20/25 parathyroid hyperplasias. Snail and Twist positive cells were homogeneously distributed throughout the gland. However, in all nine parathyroid carcinomas, membranous E-cadherin staining was lost. In addition, the expression pattern of Snail and Twist was changed and mostly limited to the invasive front of cancer tissue samples. CONCLUSION: Expression of Snail and Twist at the invasive front and consecutive loss of E-cadherin in parathyroid carcinomas suggests a key role of EMT in the tumorigenesis of this cancer. The unique expression pattern could help to distinguish between an adenoma and a non-metastatic carcinoma. Loss of E-cadherin and change of the expression pattern of Snail and Twist together should result in an en bloc resection or a close follow-up.

Is rapid preparation for thyroidectomy in severe Graves' disease beneficial? The relationship between clinical and immunohistochemical aspects.

BACKGROUND: To evaluate the effect of Lugol's Iodine (LI) on angiogenic characteristics and postthyroidectomy morbidity in patients with Graves' Disease (GD). METHODS: Medical records of 153 patients, who underwent thyroidectomies for GD between 1987 and 2006 were reviewed. LI in addition to antithyroid drugs (ATD) was administered to 16 toxic Graves' cases (group I), while 137 received ATD only (group II). In order to evaluate thyroid vascularity, immunohistochemical staining (IHS) for VEGF and CD31 for assessing microvessel density (MVD) were performed in group I, 20 random cases of group II, and 7 stochastic patients with non-toxic goiter (group III). RESULTS: Early postoperative complications were significantly higher in group I compared to group II: (transient recurrent nerve palsy (P < 0.04), transient hypocalcemia (P < 0.02), and postoperative bleeding (P < 0.003)). Meanwhile permanent complications were not significantly different. VEGF-IHS revealed ten patients of group I (62.5%) to have positive staining compared to only 3 (15%) of group II. All patients of group III stained positive. The expression of VEGF was more intense in group I as compared to group II (P < 0.02). However, no significant difference of MVD among all groups was recorded. CONCLUSION: Preoperative LI treatment may be associated with increased early postoperative morbidity and did not affect thyroid vascularity.

Intrathyroidal hematopoiesis: a rare histological finding in an otherwise healthy patient and review of the literature.

BACKGROUND AND AIMS: Multinodular goiter represents the most common thyroid disease in Europe and the United States. Regressive changes like hemorrhage, infarction or fibrosis are frequently observed. Calcifications have also been detected by microscopic investigation of thyroid tissue. Extramedullary hematopoiesis has been described in almost every organ, especially in patients with hematologic diseases. However, true bone formation is uncommon and to date only two cases of metaplastic bone formation with extramedullary hematopoiesis in the thyroid have been reported in the literature. MATERIALS AND METHODS: We present a case of total thyroidectomy due to multinodular goiter harboring an area of mature bone and hematopoiesis in an otherwise healthy female patient. Furthermore, we reviewed and summarized for the first time all available cases from the literature. RESULTS: We report the third case of metaplastic bone formation with foci of hematopoietic tissue in the thyroid gland. All three patients were young females without any obvious stimulus for extramedullary hematopoiesis. CONCLUSION: Isolated extramedullary hematopoiesis seems to be more frequent in the thyroid gland than metaplastic bone formation with hematopoiesis, particularly in older people with underlying hematologic disorders. It also represents an important differential diagnosis of anaplastic carcinoma of the thyroid, particularly in intra-operative frozen sections and fine-needle aspiration biopsy.