Compact portable higher harmonic generation microscopy for the real time assessment of unprocessed thyroid tissue.

During thyroid surgery fast and reliable intra-operative pathological feedback has the potential to avoid a two-stage procedure and significantly reduce health care costs in patients undergoing a diagnostic hemithyroidectomy (HT). We explored higher harmonic generation (HHG) microscopy, which combines second harmonic generation (SHG), third harmonic generation (THG), and multiphoton excited autofluorescence (MPEF) for this purpose. With a compact, portable HHG microscope, images of freshly excised healthy tissue, benign nodules (follicular adenoma) and malignant tissue (papillary carcinoma, follicular carcinoma and spindle cell carcinoma) were recorded. The images were generated on unprocessed tissue within minutes and show relevant morphological thyroid structures in good accordance with the histology images. The thyroid follicle architecture, cells, cell nuclei (THG), collagen organization (SHG) and the distribution of thyroglobulin and/or thyroid hormones T3 or T4 (MPEF) could be visualized. We conclude that SHG/THG/MPEF imaging is a promising tool for clinical intraoperative assessment of thyroid tissue.

Incidence and oncological implication of adrenal incidentalomas in esophageal cancer patients.

Adrenal incidentalomas are regularly encountered during imaging for esophageal cancer patients, but their oncological significance remains unknown. This study aimed to describe the incidence and etiology of adrenal incidentalomas observed throughout the diagnostic workup. This retrospective cohort study included all esophageal cancer patients referred to or diagnosed in the Amsterdam UMC between January 2012 and December 2016. Radiology and multidisciplinary team meeting reports were reviewed for adrenal incidentalomas. In case of adrenal incidentaloma, the 18FDG-PET/CT was reassessed by a radiologist blinded for the original report. In case of a metachronous incidentaloma during follow-up, visibility on previous imaging was reassessed. Primary outcome was the incidence, etiology and oncological consequence of synchronous adrenal incidentalomas. This study included 1,164 esophageal cancer patients, with a median age of 66 years. Patients were predominantly male (76.1%) and the majority had an adenocarcinoma (69.0%). Adrenal incidentalomas were documented in 138 patients (11.9%) during the diagnostic workup. At primary esophageal cancer workup, 22 incidentalomas proved malignant. However, follow-up showed that four incidentalomas were inaccurately diagnosed as benign and three malignant incidentalomas were visible on staging imaging but initially missed. Stage migration occurred in 15 of 22 (68.2%), but this would have been higher if none were missed or inaccurately diagnosed. The oncological impact of adrenal incidentalomas in patients with esophageal cancer is significant as a considerable part of incidentalomas changed treatment intent from curative to palliative. As stage migration is likely, pathological examination of a synchronous adrenal incidentaloma should be weighted in mind.

Thyroid Lobectomy for Low-Risk 1-4 CM Papillary Thyroid Cancer is not Associated with Increased Recurrence Rates in the Dutch Population with a Restricted Diagnostic Work-Up.

INTRODUCTION: The 2015 American Thyroid Association guidelines recommend to de-escalate treatment such as Thyroid lobectomy instead of total thyroidectomy for 1-4 cm papillary thyroid cancer (PTC). Dutch guidelines endorse restricted work-up for thyroid incidentalomas recommending only fine needle aspiration in case of a 'palpable thyroid nodule'. This diagnostic work-up algorithm may result in the identification of less indolent PTCs and may lead to a patient population with relatively more aggressive PTCs. This study aims to retrospectively analyze recurrence rates of low-risk 1-4 cm PTC in the Netherlands. METHODS: From the national cancer registry, patients with low-risk 1-4 cm PTC between 2005 and 2015 were included for analysis. Disease free survival (DFS) and overall survival were compared between patients who underwent TT ± RAI and TL without RAI. Post-hoc propensity score analysis was performed correcting for age, sex, T-stage, and N-stage. RESULTS: In total 901 patients were included, of which 711 (78.9%) were females, with a median follow-up of 7.7 years. TT was performed in 893 (94.8%) patients. Recurrence occurred in 23 (2.6%) patients. Multivariable analysis showed no significant correlation between extent of surgery and DFS (p = 0.978), or overall survival (p = 0.590). After propensity score matching, multivariable analysis showed no significant difference on extent of surgery and recurrence. CONCLUSION: Low-risk PTC patients with 1-4 cm tumor who underwent TL showed similar recurrence rates as those who underwent TT ± adjuvant RAI, which suggests that TL can be sufficient in treating low-risk 1-4 cm PTC, possibly reducing morbidity of these patients in the Netherlands.

Fluorescence angiography guided resection of small bowel neuroendocrine neoplasms with mesenteric lymph node metastases.

BACKGROUND: Surgery for small bowel neuroendocrine neoplasms (SB-NEN) might result in vascular compromise of the remaining bowel due to resection of lymph node metastases in close proximity to main mesenteric vessels. Fluorescence angiography (FA) has been described as a safe technique to assess perfusion during gastro-intestinal surgery. This study aimed to evaluate the potential value of intraoperative FA during surgery for SB-NEN. METHODS: This study included patients undergoing surgery for SB-NEN of any stage. The planned level of transection was marked by the surgeon, after which FA using indocyanine green (ICG) was performed. The primary study outcome was change in management due to FA. RESULTS: Ten consecutive patients with SB-NEN were included, all with metastatic lymph nodes close to main mesenteric vessels. FA use led to management changes in eight patients (80%); four patients had less bowel resected with a preserved length of 5-35 cm. The other four patients had more extended bowel resections with an additional length varying from 3 to 25 cm. The median postoperative stay was 4 days (interquartile range 4-6). No anastomotic leakage occurred. CONCLUSION: This is the first known series describing preliminary results of FA during SB-NEN surgery. FA led to a management change in 80% of patients with better tailoring the extent of resection of small bowel. Structural implementation of FA to assess small bowel perfusion after dissection for small bowel NET results in change of management, either by preserving small bowel or resecting ill-perfused small bowel.

Hemithyroidectomy versus total thyroidectomy for well differentiated T1-2 N0 thyroid cancer: systematic review and meta-analysis.

BACKGROUND: Evidence for limiting the extent of surgery in patients with low-risk thyroid cancer is lacking. METHODS: A systematic search was performed according to the PRISMA and MOOSE guidelines to assess the effect of total thyroidectomy (TT) with or without radioactive iodine (RAI) treatment versus hemithyroidectomy (HT) on recurrence and overall mortality in patients with differentiated (papillary or follicular) T1-2 N0 thyroid cancer. PubMed, Embase and Cochrane databases were searched, and two authors independently assessed the articles. RESULTS: A total of ten eligible articles were identified. All were observational cohort series, representing a total of 23 134 patients, of which 17 699 were available for meta-analysis. Six studies included patients who had TT followed by RAI treatment. The pooled recurrence rate after TT ± RAI and HT was 2·3 and 2·8 per cent respectively (odds ratio (OR) 1·12, 95 per cent c.i. 0·82 to 1·53; P = 0·48). The pooled 20-year overall survival rate after TT ± RAI was 96·8 per cent, compared with 97·4 per cent for HT (OR 1·30, 0·71 to 2·37; P = 0·40). Overall, higher complication rates were found in the TT ± RAI group. CONCLUSION: Recurrence rates after HT for treatment of well differentiated T1-2 N0 thyroid cancer were similar to those after TT ± RAI, with a lower incidence of treatment-related complications.

ANTECEDENTES: No hay evidencia para limitar la extensión de la cirugía en pacientes con cáncer de tiroides de bajo riesgo. MÉTODOS: Se realizó una búsqueda sistemática siguiendo las recomendaciones PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) y MOOSE (Meta-analysis of Observational Studies in Epidemiology) para evaluar el efecto de la tiroidectomía total (TT) +/− yodo radioactivo (radioactive iodine treatment, RAI) versus hemitiroidectomía (HT) en la recidiva y en la mortalidad global en el cáncer de tiroides diferenciado (papilar/folicular) T1-T2N0. Se realizaron búsquedas en las bases de datos PubMed, Embase y Cochrane, y dos autores evaluaron los artículos de forma independiente. RESULTADOS: Se identificaron un total de 10 artículos de interés. Todos ellos eran estudios de cohortes observacionales, con un total de 23.134 pacientes, de los cuales 17.699 se incluyeron en el metaanálisis. En seis estudios, los pacientes fueron tratados mediante TT seguida de RAI. Las tasas agrupadas de recidiva tras TT +/− RAI y HT fueron 2,3% and 2,8%, respectivamente (razón de oportunidades, odds ratio, OR = 1,12, i.c. del 95% 0,82-1,54, P = 0.48). La supervivencia global a 20 años de TT +/− RAI fue del 96,8% en comparación con el 97,4% para la HT (OR = 1,30, i.c. del 95% 0,71-2,37, P = 0,40). Globalmente, se observaron más complicaciones en el grupo de TT +/− RAI. CONCLUSIÓN: Esta revisión sistemática con metaanálisis demuestra tasas de recidiva similares tras una HT para el tratamiento del cáncer de tiroides T1-2N0 bien diferenciado en comparación con TT +/− RAI, con una menor incidencia de complicaciones relacionadas con el tratamiento.

Robotic Enucleation of an Intra-Pancreatic Insulinoma in the Pancreatic Head.

Pancreatic parenchyma sparing surgery for insulinomas avoids the risk of endocrine and exocrine insufficiency, and potential high-risk anastomoses associated with pancreatic resection. Robotic surgery may be used as an alternative for open pancreatic enucleation without compromising dexterity and 3D-vision. We present the case of a 42-year old woman who presented with sweating, tremor and episodes of hypoglycemia. A fasting test confirmed endogenic insulin overproduction. After inconclusive CT- and MRI imaging, endoscopic ultrasonography showed a hypoechoic lesion, which was fully within the pancreatic head. Although consent was obtained for pancreatoduodenectomy, robotic enucleation seemed feasible. After mobilization, intraoperative ultrasonography was used to identify the lesion and its relation with the pancreatic duct. Dissection was performed using a traction suture, hot shears and bipolar diathermia. A sealant patch was applied for hemostasis and a drain placed. The patient developed a grade B pancreatic fistula for which endoscopic sphincterotomy was performed; the surgical drain could be removed in the outpatient clinic after 20 days. Prospective studies should confirm the short- and long-term benefits of robotic enucleation of insulinomas.

Parathyroidectomy versus cinacalcet for tertiary hyperparathyroidism; a retrospective analysis.

INTRODUCTION: Tertiary hyperparathyroidism (tHPT), i.e., persistent HPT after kidney transplantation, affects 17-50% of transplant recipients. Treatment of tHPT is mandatory since persistently elevated PTH concentrations after KTx increase the risk of renal allograft dysfunction and osteoporosis. The introduction of cinacalcet in 2004 seemed to offer a medical treatment alternative to parathyroidectomy (PTx). However, the optimal management of tHPT remains unclear. METHODS: A retrospective analysis was performed on patients receiving a kidney transplantation (KT) in two academic centers in the Netherlands. Thirty patients undergoing PTx within 3 years of transplantation and 64 patients treated with cinacalcet 1 year after transplantation for tHPT were included. Primary outcomes were serum calcium and PTH concentrations 1 year after KT and after PTx. RESULTS: Serum calcium normalized in both the cinacalcet and the PTx patients. PTH concentrations remained above the upper limit of normal (median 22.0 pmol/L) 1 year after KT, but returned to within the normal range in the PTx group (median 3.7 pmol/L). Side effects of cinacalcet were difficult to assess; minor complications occurred in three patients. Re-exploration due to persistent tHPT was performed in three (10%) patients. CONCLUSION: In patients with tHPT, cinacalcet normalizes serum calcium, but does not lead to a normalization of serum PTH concentrations. In contrast, PTx leads to a normalization of both serum calcium and PTH concentrations. These findings suggest that PTx is the treatment of choice for tHPT.

Influence of neural monitoring during thyroid surgery on nerve integrity and postoperative vocal function.

BACKGROUND: Integrity of the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (EBSLN) can be checked by intraoperative nerve monitoring (IONM) after visualization. The aim of this study was to determine the prevalence and nature of voice dysfunction following thyroid surgery with routine IONM. METHODS: Thyroidectomies were performed with routine division of strap muscles and nerve monitoring to confirm integrity of the RLN and EBSLN following dissection. Patients were assessed for vocal function before surgery and at 1 and 3 months after operation. Assessment included use of the Voice Handicap Index (VHI) 10, maximum phonation time, fundamental frequency, pitch range, harmonic to noise ratio, cepstral peak prominence and smoothed cepstral peak prominence. RESULTS: A total of 172 nerves at risk were analysed in 102 consecutive patients undergoing elective thyroid surgery. In 23·3 per cent of EBSLNs and 0·6 per cent of RLNs nerve identification required the assistance of IONM in addition to visualization. Nerve integrity was confirmed during surgery for 98·8 per cent of EBSLNs and 98·3 per cent of RLNs. There were no differences between preoperative and postoperative VHI-10 scores. Acoustic voice assessment showed small changes in maximum phonation time at 1 and 3 months after surgery. CONCLUSION: Where there is routine division of strap muscles, thyroidectomy using nerve monitoring confirmation of RLN and EBSLN function following dissection results in no clinically significant voice change.

[Intraoperative neuromonitoring in endocrine surgery: when is it appropriate?] / Intraoperatieve neuromonitoring bij endocriene chirurgie: wanneer zinvol?

The use of intraoperative neuromonitoring (IONM) in thyroid surgery has steadily increased in recent years. This technique helps to identify different nerves in and around the operation site, such as the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve. Particularly in patients who undergo a second operation or a complex procedure for malignancy, the technique's value has been demonstrated. However, in non-complex thyroid operations the risk of vocal cord paresis due to iatrogenic injury of the RLN is 0.1%. Therefore, high quality research with sufficient power to assess the effect of IONM on prevention of vocal cord paresis is scarce, and the routine use of IONM in thyroid surgery is currently not indicated.

Multicentre study evaluating the surgical learning curve for posterior retroperitoneoscopic adrenalectomy.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy has gained international popularity in the past decade. Despite major advantages, including shorter duration of operation, minimal blood loss and decreased postoperative pain, many surgeons still prefer laparoscopic transperitoneal adrenalectomy. It is likely that the unfamiliar anatomical environment, smaller working space and long learning curve impede implementation. The present study assessed the number of procedures required to fulfil the surgical learning curve for posterior retroperitoneoscopic adrenalectomy. METHODS: The first consecutive posterior retroperitoneoscopic adrenalectomies performed by four surgical teams from university centres in three different countries were analysed. The primary outcome measure was duration of operation. Secondary outcomes were conversion to an open or laparoscopic transperitoneal approach, complications and recovery time. The learning curve cumulative sum (LC-CUSUM) was used to assess the learning curves for each surgical team. RESULTS: A total of 181 surgical procedures performed by four surgical teams were analysed. The median age of the patients was 57 (range 15-84) years and 61·3 per cent were female. Median tumour size was 25 (range 4-85) mm. There were no significant differences in patient characteristics and tumour size between the teams. The median duration of operation was 89 (range 29-265) min. There were 35 perioperative and postoperative complications among the 181 patients (18·8 per cent); 17 of 27 postoperative complications were grade 1. A total of nine conversions to open procedures (5·0 per cent) were observed. The LC-CUSUM analysis showed that competency was achieved after a range of 24-42 procedures. CONCLUSION: In specialized endocrine surgical centres between 24 and 42 procedures are required to fulfil the entire surgical learning curve for the posterior retroperitoneoscopic adrenalectomy.

Evaluation of collimated polarized light imaging for real-time intraoperative selective nerve identification in the human hand.

Intraoperative peripheral nerve lesions are common complications due to misidentification and limitations of surgical nerve identification. This study validates a real-time non-invasive intraoperative method of nerve identification. Long working distance collimated polarized light imaging (CPLi) was used to identify peripheral radial nerve branches in a human cadaver hand by their nerve specific anisotropic optical reflection. Seven ex situ and six in situ samples were examined for nerves, resulting after histological validation, in a 100% positive correct score (CPLi) versus 77% (surgeon). Nerves were visible during a clinical in vivo observation using CPLi. Therefore CPLi is a promising technique for intraoperative nerve identification.

Morphological aspects of surgical meshes as a risk factor for bacterial colonization.

BACKGROUND: Prosthetic meshes are increasingly popular in abdominal wall reconstructive surgery owing to a reduction in hernia recurrence rate. Individual meshes have been evaluated with respect to the formation of infectious biofilms, but no comprehensive comparison yet exists. The aim of this study was to evaluate the effect of the material and morphology of surgical meshes on biofilm growth. METHODS: Biofilms of a coagulase-negative staphylococcus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were grown in vitro on different meshes. Intact biofilms were stained fluorescently and evaluated with confocal laser scanning microscopy to distinguish dead from live bacteria and slime. RESULTS: Numbers of adhering bacteria and the amount of slime in the biofilm were dependent on the morphology of the mesh. Hydrophobicity and the presence of niches in multifilament meshes contributed most to increased biofilm growth. CONCLUSION: The morphological properties of surgical meshes as well as their hydrophobicity influence bacterial growth and slime production. Differences in slime production may explain why the effectiveness of antibiotic treatment varies for different types of mesh.