Christoph Ulmer

Real-time monitoring of the recurrent laryngeal nerve: An observational clinical trial

BACKGROUND A variety of tools has been developed to identify nerve structures and to lower the risk of nerval injury during thyroid surgery. These tools are usually based on intermittent electrophysiological tracing of the nerves, but its use is still associated with permanent recurrent laryngeal nerve (RLN) injury. We are now presenting the results of the implementation of a novel real-time nerve monitoring system, based on a new vagal nerve cuff electrode. METHODS Nineteen consecutive patients scheduled for thyroid surgery (17 with benign, 2 with malignant disease), were enrolled in this observational trial. The flexible cuff electrode was implanted during each operation and atraumatically surrounded the vagal nerve. The evoked potentials were sensed by standard thyroid electrodes. Electrical stimulation and recording were achieved through a multichannel electromyography (EMG) system. The signal analysis was performed in real-time by specially designed software. RESULTS The cuff electrode did not cause any complications during or after the surgery. In all patients, stable and reproducible signals were easily evoked. The mean time required to place the electrode was 6.5 min. The mean overall vagal nerve stimulation time was 65 min. No permanent RLN lesions were detected in any patient. One patient with a postoperative bleeding from a strap muscle vein required a wound revision, which was performed without nerve monitoring. This patient experienced a temporary partial impairment of the left vocal cord. No hypoparathyroidism was observed in any patient postoperatively. CONCLUSIONS The presented technique of real-time continuous RLN monitoring by stimulation of the vagal nerve is feasible, safe, reproducible, and easy to perform. In addition, this new system is compatible with existing equipment and can be used as an add-on with conventional nerve monitoring devices during thyroid surgery.

A new system for continuous recurrent laryngeal nerve monitoring

Existing nerve monitoring devices in thyroid surgery are ‐ except for one ‐ mainly intermittently working nerve identification tools. We present a new vagal electrode which allows true continuous monitoring of the recurrent laryngeal nerve (RLN). The electrode was designed as a tripolar hybrid cuff electrode consisting of polyimide, gold and platinum layers embedded in a flexible silicon cuff which can be opened at the long side for introducing the nerve. It is fully implantable and atraumatic. The evoked potentials are sensed by standard thyroid electrodes. Real‐time signal analysis and audio feedback are achieved by specially designed software. Homogeneous and stable signals were recorded throughout the operations. Thus real‐time computer‐based signal analysis was possible. Evoked potentials reached 300–900 mV. Mean time to place the cuff electrode was 5.5 min. The nerve was stimulated a mean of 63 min (range 55–99 min). No RLN lesions were detected postoperatively. The new vagal electrode was easy to handle and led to stable and reproducible signals. The stimulation current could be kept extremely low due to the special geometry of the electrode. It offers the possibility for uninterrupted, continuous laryngeal nerve monitoring in thyroid surgery. In an ongoing clinical trial its compatibility as an add‐on for existing nerve monitoring devices is being tested.

Impact of continuous intraoperative neuromonitoring on autonomic nervous system during thyroid surgery

Continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation (VNS) is a new option for recurrent laryngeal nerve (RLN) protection during thyroid surgery. The aim of this study was to evaluate the safety of VNS for CIONM and to assess its effects on the autonomic nervous system (ANS) through analyzing heart rate variability (HRV).

Safety of neural monitoring in thyroid surgery

During thyroid surgery, the functional integrity of the recurrent laryngeal nerve (RLN) is not only threatened by direct nerve injury resulting from accidental transection, clipping or ligation. In fact, indirect trauma, e.g. traction and compression occurring repeatedly throughout gland dissection, contribute to long-term nerve impairment. In order to avoid RLN lesions and preserve nerve function the surgeon must adhere to and comply with a strict standardized intraoperative neuromonitoring (IONM) technique to preserve results, quality and safety. IONM should be a team work between the surgeon and the anesthesiologist.

Safety analysis of vagal nerve stimulation for continuous nerve monitoring during thyroid surgery.

Intraoperative neuromonitoring (IONM) facilitates recurrent laryngeal nerve (RLN) identification, but various studies affirm virtually unchanged postoperative RLN palsy rates. Several authors meanwhile suggest continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation (VNS) to improve RLN protection. However, knowledge of side effects of electrical VNS derives mainly from its therapeutic applications in the fields of neurology and psychiatry. The presented study was conducted to further evaluate the safety of CIONM and identify possible VNS related side effects.

Encapsulating peritoneal sclerosis: a rare, serious but potentially curable complication of peritoneal dialysis–experience of a referral centre in Germany

BACKGROUND Chronic peritoneal dialysis (PD) can be complicated by encapsulating peritoneal sclerosis (EPS), the most severe complication associated with long-term PD. METHODS In this study, we retrospectively analysed 49 EPS patients regarding clinical presentation, histopathological findings, treatment and long-term clinical outcome at our referral centre. Patients were divided into two clinical categories: severe and mild/moderate. RESULTS All patients in the severe group and most patients in the mild/moderate group had symptoms consistent with EPS. The most common computed tomographic findings were peritoneal thickening in both groups. Small bowel dilatation was frequently present in the severe group. The time of onset of symptoms consistent with EPS to the surgical procedure was median 5 months with an inter-quartile range of 2-12 months in the severe group. To date, 25 of 31 patients in the severe group (follow-up 45.6 ± 39.0 months after surgery) are alive. In the mild/moderate group, 8 of 11 patients are alive (follow-up 41.6 ± 21.6 months). The histological features were consistent with EPS in all biopsies. CONCLUSIONS The outcome of patients even with severe EPS is not worse. It is a precondition that these patients are treated in specialized referral centres. The time of first clinical symptoms consistent with EPS to requirement of surgery is very short. Earlier diagnosis of the disease is mandatory, even in asymptomatic patients.

Difference in the expression of hormone receptors and fibrotic markers in the human peritoneum--implications for therapeutic targets to prevent encapsulating peritoneal sclerosis.

♦ Objective: Encapsulating peritoneal sclerosis (EPS) is a rare but life-threatening complication of peritoneal dialysis (PD). The optimal management of patients with EPS is uncertain. In the present study, we investigated differences in the expression of nuclear receptors [progesterone (PR), androgen (AR), vitamin D (VDR), and glucocorticoid (GCR)] in the human peritoneum. We also investigated estrogen receptor (ER), matrix metalloproteinase 9 (MMP9), and transforming growth factor β1 (TGFβ1) in the context of their potential role in tamoxifen therapy. ♦ Methods: We analyzed clinical and histologic characteristics of 72 peritoneal biopsy specimens (22 from EPS patients, 11 from PD patients, 15 from uremic patients, and 24 from control subjects undergoing hernia repair). For immunophenotyping, we used antibodies against VDR, GCR, ER, PR, AR, MMP9, and TGFβ1. ♦ Results: In human peritoneum, VDR and GCR are highly expressed (98.6% and 87.3% respectively). Except in the case of VDR (p = 0.0012), we observed no significant difference in receptor expression between the groups. Expression of ER and PR was sparse (11.4% and 31% respectively), with higher expression in women, and AR was absent. Minimal MMP9 expression and moderate TGFβ1 expression were observed in all groups. The differences between the groups were nonsignificant. ♦ Conclusions: Nuclear receptors are present in human peritoneum. Except in the case of VDR, the pattern for any one group is nonspecific. Glucocorticoids, vitamin D, and angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers (via the vitamin D/angiotensin II pathway) might be suitable interventions for preservation of the integrity of the peritoneal membrane. The mechanism of action of tamoxifen is still not elucidated, ER expression in the peritoneum is sparse, and data about the studied pathways (MMP9, TGFβ) are inconsistent.

Efficacy and morbidity of surgical therapy in late-stage encapsulating peritoneal sclerosis

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis composed of chronic abdominal pain, chronic ileus, and severe malnutrition. Operative therapy for EPS is a complex procedure, including perionectomy and enterolysis (PEEL). In contrast to simple adhesiolysis, PEEL comprises a restitution of intestinal passage and prevention of recurrent disease by decapsulation and partial deserosation. METHODS We reviewed the treatment of patients with EPS at our referral center regarding perioperative morbidity, mortality, and long-term outcome. Only patients who underwent PEEL were included. Preoperative general status was ascertained by APACHE-II score and body mass index. Postoperative morbidity was stratified into minor and major complications. RESULTS Between the years 2003 and 2010, 26 of 45 patients with late-stage EPS underwent PEEL. Median age was 54 years, APACHE-II score was 15, and body mass index was 21 kg/m². To achieve intestinal function, 9 bowel resections with immediate anastomoses were necessary. Eleven patients (37%) received a complete parietal peritonectomy. Overall morbidity was 44%, with minor complications in 2 patients (7%) and major complications in 11 patients (31%). Three patients (10%) died within the first year after operative treatment. CONCLUSION PEEL is a treatment option that can be performed with low mortality and acceptable morbidity. It is a precondition that these patients are treated in specialized referral centers.

Incidence of and risk factors for hungry bone syndrome in 84 patients with secondary hyperparathyroidism

Introduction Secondary hyperparathyroidism develops in nearly all patients with end-stage renal disease. Parathyroidectomy is often performed when medical therapy fails. The most common postoperative complication, hungry bone syndrome (HBS), requires early recognition and treatment. Materials and methods A total of 84 patients who underwent parathyroidectomy because of secondary hyperparathyroidism were investigated. Detailed analysis of laboratory parameters (calcium, phosphate, parathyroid hormone, hemoglobin, and urea levels) and baseline characteristics (age at time of surgery, duration of renal replacement therapy, and medication) was performed to detect preoperative predictors for the development of HBS. Results Average overall follow-up of the cohort was 4.7 years. Within this time frame, 13 of 84 patients had to undergo a second surgery because of recurrent disease, and HBS occurred in 51.2%. Only decreased preoperative calcium levels and younger age at time of surgery were significant predictors of HBS. Minimal levels of calcium were detected 3 weeks after surgery. Preoperative vitamin D therapy could not prevent HBS and could not shorten the duration of intravenous calcium supplementation. Conclusion HBS is a very common complication after parathyroidectomy. Younger patients and patients with low preoperative calcium levels were at higher risk for the development of HBS. Remarkably, preoperative vitamin D therapy could not prevent HBS and had no impact on the length of intravenous calcium supplementation. Intensive monitoring of calcium levels must be performed for at least 3 weeks after surgery.

Histological criteria for encapsulating peritoneal sclerosis - a standardized approach.

Background The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPS Methods We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients. Results The following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%. Conclusion The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database.