Background. Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the ...influence of an α-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without α-receptor blockade undergoing surgery for catecholamine producing tumours.
Methods. Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) α-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI).
Results. No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024).
Conclusions. Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an α-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative α- receptor blockade for phaeochromocytoma surgery demands further study.
Introduction
Laryngeal ultrasound has been increasingly used for the evaluation of the vocal cords mobility after thyroid and parathyroid surgery. The sensitivity and positive predictive value of the ...method are reported to be higher than 80%. Nevertheless, the visualization rate in male patients remains low; therefore, ultrasound is not attractive for the perioperative workup in those patients. In the present study, we evaluate the ability to improve the visualization rate for male patients by using a gel pad as an interface between the skin and the ultrasound probe.
Methods and Materials
Between December 2018 and January 2019, 92 male patients (mean age 49 years; range: 20–80 years) referred to our hospital with different thyroid pathologies received a laryngeal ultrasound without (TLUS) and subsequently with gel pad (G-TLUS). TLUS was performed by B-scan (probe 5–13 MHz, aperture 40 mm). The data were prospectively collected and statistically analyzed.
Results
The visualization rate in the TLUS group was 35% (32 out of 92 patients). The use of the gel pad could increase the rate to 78% (
p
< 0.0001). For both groups, visualization rates are lower in older patients (> 50 years) compared to younger individuals (TLUS: 25% vs. 45%,
p
< 0.05; G-TLUS: 75% vs 82%,
p
= 0.45).
Conclusion
The gel pad significantly improves the vocal cord visualization rate in male patients and should be used routinely.
Background
We analyze the long‐term outcome of surgery for Cushing's syndrome (CS) and the influence of the extent of surgical resection on the duration of postoperative cortisone substitution.
...Methods
One‐hundred forty‐one patients (129 female, 12 males; mean age: 45.7 ± 12.8 years) operated between January 2000 to June 2020 were included in the analysis. Patients suffered from manifest (124) or subclinical (17) CS due to benign unilateral adrenal neoplasia. All tumors were removed by the posterior retroperitoneoscopic approach. 105 patients had total (TA) and 36 partial (PA) adrenalectomies. All patients were discharged with ongoing corticosteroid supplementation therapy.
Results
Follow‐up data could be obtained for 83 patients. Twenty‐four (1 male, 23 females; mean age 42.3 years) underwent PA and 59 TA (6 males, 53 females; mean age 44.6 years). Mean follow‐up time was 107 ± 68 months (range: 6–243 months). The median duration of postoperative corticosteroid therapy was 9.5 months after PA and 11 months after TA (p = 0.1). Significantly, more patients after total adrenalectomy required corticosteroid therapy for more than 24 months (25% vs. 4%; p = 0.03). Recurrent ipsilateral disease occurred in one case after partial adrenalectomy and was treated by completion adrenalectomy. A case of contralateral recurrence associated with subclinical Cushing's syndrome was observed after total adrenalectomy.
Conclusions
The risk of local recurrence after partial adrenalectomy in CS is low. Cortical‐sparing surgery may shorten corticosteroid supplementation therapy after surgery.
Background
Surgery for catecholamine‐producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but ...none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected.
Methods
Twenty‐one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α‐receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality.
Results
Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α‐receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex‐sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α‐receptor blockade and 0·9 per cent (3 of 343) among patients without α‐receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non‐pretreated patients.
Conclusion
There is substantial variability in the perioperative management of catecholamine‐producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.
Antecedentes
La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros.
Métodos
Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000‐2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria.
Resultados
Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente.
Conclusión
Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.
Morbidity and mortality rates are difficult to determine in rare diseases like phaeochromocytoma. To date there has been no randomized study of the perioperative management of these patients. Therefore, an international and interdisciplinary effort was made to provide a broad overview of the current management of phaeochromocytoma.
Adverse effects frequent with preoperative blocking
For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow ...precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours.
In order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16).
Concerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist.
miRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential.
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the ...expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 was also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Moreover, depletion of PFKFB4-attenuated cellular biosynthetic activity and resulted in the accumulation of reactive oxygen species and cell death in the absence of p53. Finally, silencing of PFKFB4-induced apoptosis in p53-deficient cancer cells in vivo and interfered with tumour growth. These results demonstrate that PFKFB4 is essential to support anabolic metabolism in p53-deficient cancer cells and suggest that inhibition of PFKFB4 could be an effective strategy for cancer treatment.
Diffusion tensor imaging (DTI) can noninvasively quantify white matter (WM) integrity. Although its application in adult traumatic brain injury (TBI) is common, few studies in children have been ...reported. The purposes of this study were to examine the alteration of fractional anisotropy (FA) in children with TBI experienced during early childhood and to quantify the association between FA and injury severity.
FA was assessed in 9 children with TBI (age = 7.89 +/- 1.00 years; Glasgow Coma Scale GCS = 10.11 +/- 4.68) and a control group of 12 children with orthopedic injuries without central nervous system involvement (age = 7.51 +/- 0.95 years). All of the subjects were at minimum 12 months after injury. We examined group differences in a series of predetermined WM regions of interest with t test analysis. We subsequently conducted a voxel-wise comparison with Spearman partial correlation analysis. Correlations between FA and injury severity were also calculated on a voxel-wise basis.
FA values were significantly reduced in the TBI group in genu of corpus callosum (CC), posterior limb of internal capsule (PLIC), superior longitudinal fasciculus (SLF), superior fronto-occipital fasciculus (SFO), and centrum semiovale (CS). GCS scores were positively correlated with FA in several WM areas including CC, PLIC, SLF, CS, SFO, and inferior fronto-occipital fasciculus (IFO).
This DTI study provides evidence that WM integrity remains abnormal in children with moderate-to-severe TBI experienced during early childhood and that injury severity correlated strongly with FA.
Purpose
Visualization and precise dissection of the parathyroid glands are a crucial step of thyroidectomy. Moreover, identification of parathyroid adenoma in patients with primary ...hyperparathyroidism can be challenging due to the possible abnormal location of the enlarged parathyroid. Near-infrared fluorescence (NIR) can be adopted during video-assisted neck surgery in addition to standard endoscopic magnification to enhance the visualization of the parathyroid tissue.
Methods
Between July and August 2017, five patients (one male, four females) underwent video-assisted neck surgery at our hospital. One patient suffered from primary hyperparathyroidism. The four remaining patients underwent thyroidectomy for multinodular goiter or Graves’ disease. The parathyroid glands were firstly identified by the video-assisted approach and then confirmed by the NIR visualization of the endogenous autofluorescence of the parathyroid tissue. Low-dose (2.5 mg/ml) indocyanine green was administered to visualize the vascular supply during and/or after the dissection. The standard dose of 2.5 mg (1 ml per injection) was used to allow repeated injection during the same procedure.
Results
An endogenous parathyroid autofluorescence could be visualized by the NIR camera in all patients. The right upper parathyroid adenoma could be detected prior to fully dissection of the gland from the surrounding tissue. Twelve out of 16 parathyroid glands have been visually identified during four total thyroidectomies. Eleven glands showed an autofluorescence prior to indocyanine green (ICG) injection. Further, ICG injection has been used for guiding the dissection of the gland in three cases and for confirmation of the vascular supply at the end of the procedure in the remaining cases. There were neither intraoperative nor postoperative complications.
Conclusion
The 5-mm 30° NIR camera allows for enhanced visualization of the parathyroid tissue during video-assisted thyroidectomy. This promising tool can become standard for video-assisted neck surgery.
Background
Treatment of postoperative chylothorax can be challenging. Conservative treatment and/or surgical management by means of open or minimally invasive thoracic duct ligation for persistent ...chylothorax are accepted therapeutic options. We present a new retroperitoneoscopic approach for thoracic duct ligation.
Methods
Between January 2006 and May 2017, posterior retroperitoneoscopic thoracic duct ligation was performed in four patients. The thoracic duct was identified transdiaphragmatically and ligated cranially to the cisterna chyli using absorbable clips.
Results
Retroperitoneoscopic ligation resulted in a complete and lasting chylothorax resolution in three patients and marked improvement in a fourth one. Mean operative time was 86 min (range 40–135). There were no perioperative or postoperative complications.
Conclusions
Retroperitoneoscopic thoracic duct ligation is feasible and safe. It allows for a precise anatomical exploration of the thoracic duct caudally to the chyle leak, avoiding the previous operative field and resulting in minimal morbidity. In patients with persistent chylothorax, our approach provides an additional therapeutic option.
Background
A surgical approach preserving functional adrenal tissue allows biochemical cure while avoiding the need for lifelong steroid replacement. The aim of this experimental study was to ...evaluate the impact of intraoperative imaging during bilateral partial adrenalectomy on remnant perfusion and function.
Methods
Five pigs underwent bilateral posterior retroperitoneoscopic central adrenal gland division (9 divided glands, 1 undivided). Intraoperative perfusion assessment included computer‐assisted quantitative fluorescence imaging, contrast‐enhanced CT, confocal laser endomicroscopy (CLE) and local lactate sampling. Specimen analysis after completion adrenalectomy (10 adrenal glands) comprised mitochondrial activity and electron microscopy.
Results
Fluorescence signal intensity evolution over time was significantly lower in the cranial segment of each adrenal gland (mean(s.d.) 0·052(0·057) versus 0·133(0·057) change in intensity per s for cranial versus caudal parts respectively; P = 0·020). Concordantly, intraoperative CT in the portal phase demonstrated significantly lower contrast uptake in cranial segments (P = 0·031). In CLE, fluorescein contrast was observed in all caudal segments, but in only four of nine cranial segments (P = 0·035). Imaging findings favouring caudal perfusion were congruent, with significantly lower local capillary lactate levels caudally (mean(s.d.) 5·66(5·79) versus 11·58(6·53) mmol/l for caudal versus cranial parts respectively; P = 0·008). Electron microscopy showed more necrotic cells cranially (P = 0·031). There was no disparity in mitochondrial activity (respiratory rates, reactive oxygen species and hydrogen peroxide production) between the different segments.
Conclusion
In a model of bilateral partial adrenalectomy, three intraoperative imaging modalities consistently discriminated between regular and reduced adrenal remnant perfusion. By avoiding circumferential dissection, mitochondrial function was preserved in each segment of the adrenal glands.
Surgical relevance
Preservation of adrenal tissue to maintain postoperative function is essential in bilateral and hereditary adrenal pathologies. There is interindividual variation in residual adrenocortical stress capacity, and the minimal functional remnant size is unknown.
New intraoperative imaging technologies allow improved remnant size and perfusion assessment. Fluorescence imaging and contrast‐enhanced intraoperative CT showed congruent results in evaluation of perfusion.
Intraoperative imaging can help to visualize the remnant vascular supply in partial adrenalectomy. Intraoperative assessment of perfusion may foster maximal functional tissue preservation in bilateral adrenal pathologies and procedures.
Antecedentes
Un abordaje quirúrgico que preserve la función del tejido suprarrenal permite lograr la curación bioquímica, a la vez que evita la necesidad de tratamiento sustitutivo con corticoides de por vida. El objetivo de este estudio experimental fue evaluar el impacto de las técnicas de imagen intraoperatorias en la suprarrenalectomía parcial (partial adrenalectomy, AE) bilateral sobre la perfusión y función del remanente glandular.
Métodos
Cinco cerdos fueron sometidos a una división bilateral central de la glándula suprarrenal por retroperitoneoscopia posterior (n = 9, 1 sin dividir). Durante la intervención, la evaluación de la perfusión incluyó la fluorescencia con cuantificación asistida por ordenador (Realidad Aumentada basada en la Fluorescencia, FLuorescence‐based Enhanced Reality, FLER), tomografía computarizada (computed tomography, CT), endomicroscopia con laser confocal (confocal laser endomicroscopy, CLE) y un muestreo local de lactato. El análisis de la pieza quirúrgica tras completar la AE (n = 10) incluyó actividad mitocondrial y microscopia electrónica.
Resultados
La evolución de la intensidad de la señal de fluorescencia a lo largo del tiempo (ΔI/s) fue significativamente más baja en el segmento craneal de cada una de las glándulas (0,052 ± 0,057 craneal versus 0,133 ± 0,057 caudal, P = 0,02). De forma concordante, la CT intraoperatoria en la fase portal demostró una captación de contraste significativamente más baja en los segmentos craneales (P = 0,03). En la CLE, el contraste de fluoresceína se observó en todos los segmentos caudales, pero solo en el 44% de los segmentos craneales (P = 0,04). Los hallazgos obtenidos en las pruebas de imagen favorables a la perfusión caudal fueron congruentes con niveles significativamente más bajos de lactato capilar a nivel local (11,58 ± 6,53 mmol/L craneal versus 5,66 ± 5,79 mmol/L caudal, P = 0,008). A nivel craneal, la microscopia electrónica mostró más células necróticas (P = 0,03). La actividad mitocondrial (tasas de respiración, especies reactivas de oxígeno y producción de H2O2) no mostraron disparidad entre los diferentes segmentos.
Conclusión
En un modelo de AE parcial bilateral, las tres modalidades de pruebas de imagen intraoperatorias podrían discriminar de forma consistente una perfusión regular y reducida del remanente suprarrenal. Al evitar una disección circunferencial, se preservó la función mitocondrial en cada segmento de las glándulas suprarrenales.
Currently, the minimal functional adrenal remnant size, and the impact of intraoperative imaging technologies on remnant function after partial adrenalectomy, is unknown. In the present experimental study, intraoperative perfusion assessment, using quantitative fluorescence imaging, confocal laser endomicroscopy and contrast‐enhanced CT, enabled identification of gland segments at risk. Mitochondrial function essential for steroidogenesis was preserved in all adrenal segments in this model of partial adrenalectomy.
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