Application of Ultrasound-guided Intercostal Nerve Block in Retroperitoneal Laparoscopic Nephrectomy

Purpose: Surgical stimulation causes many pathophysiological changes which are not conducive to the recovery of patients, this trail aims to investigate whether intercostal nerve block can reduce the perioperative stress response and postoperative pain in patients undergoing elective retroperitoneal laparoscopic nephrectomy.Patients and methods:40 patients were recruited and randomly assigned to Test groupand Blank group.Results: Our study found that the catecholamine and cortisol levels in two groups were higher than the baseline value after pneumoperitoneum, (P＜0.05), while the catecholamine level was lower in Test groupthan in Blank group (P＜0.05), and there is no differences of cortisol levels was observed in two groups. The catecholamines and cortisol levels of two groups were basically restored to the preoperative level after 24 hours surgery, The concentration of IL-6 and IL-10 in two groups increased at 24 hours after surgery, but there was no differences was observed between the two groups at the same point. And the usage of analgesic during operation was less in the Test group than Blank group (P＜0.05).Conclusion : Intercostal nerve block can reduce the stress response of patients undergoing retroperitoneal laparoscopic nephrectomy and reduce the usage of perioperative analgesics.Tial registration statement : This trial has been applied by the ethics Association of Chongqing cancer hospital.

Dopamine secreting pheochromocytoma and paraganglioma

Predominantly or exclusively dopamine-secreting pheochromocytoma and paraganglioma are very rare. We report a 64-year-old woman with an adrenal incidentaloma. She was normotensive and had no symptoms of catecholamine excess. The 24-hour urine catecholamine level showed normal norepinephrine (122.9 μg/day), epinephrine (24.3 μg/day), whereas markedly elevated dopamine (148,212.4 μg/day). 123I-metaiodobenzylguanidine (MIBG) scintigraphy revealed tumor uptake. After α-blockade as preoperative management, she successfully underwent laparoscopic left adrenalectomy and was finally diagnosed with an exclusively dopamine-secreting pheochromocytoma. The tumor was histologically comprised of small polygonal cells with high cellularity and was immunohistochemically positive for all three catecholamine synthesizing enzymes: tyrosine hydroxylase (very weak), dopamine β-hydroxylase (heterogeneous), and phenylethanolamine N-methyltransferase (very weak). Electron microscopy revealed very few catecholamine-containing small vesicles with a few organelles, which reflected immature cells. No biochemical or imaging evidence of recurrence or metastasis were evident 1 year after the surgery. We conducted a literature search in the Pubmed database. A total of 33 cases were collected. Our case had the second-highest 24-hour urinary dopamine excretion and was the first in which immunostaining for catecholamine synthase and electron microscopy were performed together. Histological findings in our case give a possible hypothesis that the mechanism underlying a dopamine-secreting pheochromocytoma is associated with immature catecholamine vesicles in which DBH is localized, thus resulting in inhibited conversion from dopamine to norepinephrine. We also discuss the reasons for the lack of catecholamine excess symptoms, whether preoperative management of α-blockade is needed, and the association between the prognosis and genetic mutation with an extensive literature review.

SAT-231 A Case of Metastatic Pheochromocytoma Associated with Beckwith-Wiedemann Syndrome

Introduction: Beckwith-Wiedemann Syndrome (BWS) is an autosomal dominant disorder of chromosome 11p15 that results in increased IGF-2 and CDK1NC. This leads to excessive cell proliferation and tumor formation. The following highlights a case of metastatic pheochromocytoma in a patient with BWS. Clinical Case: A 30-year-old male presented with sudden onset blurry vision without any associated complaints. His past medical history was significant for BWS. His family history was negative for uncontrolled hypertension, sudden death, thyroid cancer or hyperparathyroidism. Physical examination was notable for an elevated systolic blood pressure of 200/160 mm of hg and fundoscopy revealed features of hypertensive emergency. Laboratory investigations revealed an elevated plasma normetanephrine [10445 pg/ml (normal: <148)], metanephrine [93 pg/ml (normal: <57)], total metanephrine [10538 pg/ml (normal: <205)], epinephrine [134 pg/ml (normal:<50)], norepinephrine [23526 pg/ml (normal: 112-658), total catecholamine level [23660 (normal: 123-671pg/ml)] and dopamine [403 pg/ml (normal<30)] levels. His PTH, corrected serum calcium, gastrin, insulin, carcinoembryonic antigen, calcitonin levels and basal metabolic panel were all normal. MRI of the abdomen demonstrated bilateral adrenal nodules with a large mass encasing the celiac axis along with evidence of hepatic lesions. I-123 MIBG scan showed mild radioactive tracer uptake in the adrenal nodules and mass near the celiac axis but not in the hepatic lesions. PET scan confirmed MRI findings and was negative for any evidence of malignancy in the chest, pelvis and skeleton. MRI of the brain was negative for metastasis as well as pituitary abnormalities. Ultrasound-guided liver biopsy was positive for malignant cells that stained positive for chromogranin and synaptophysin confirming the diagnosis of metastatic pheochromocytoma. He was treated with phenoxybenzamine, diltiazem and lisinopril. He underwent cycles of cyclophosphamide, vincristine and dacarbazine. Genetic testing revealed a variant in SDHD gene which was of uncertain significance. Repeat biochemical testing on follow up after a year and a half showed a decreased plasma normetanephrine [487pg/ml] and metanephrine levels [110 pg/ml] in comparison to his levels on presentation. Repeat imaging revealed a decrease in tumor burden including bilateral adrenal nodules, celiac axis mass and hepatic metastases. Conclusion: This is an unusual case of malignant pheochromocytoma in the absence of SDHB mutation in a patient with BWS. Genetic causes in these patients are yet to be determined. However, genes H19 and KCNQ1OT1 have been implicated in addition to IGF-2 and CDK1NC

Detection of severe hypertension in a patient with neurofibromatosis type 1 during anesthesia induction: a case report

Background Neurofibromatosis type 1 has a higher prevalence of pheochromocytoma and paraganglioma than the general population: 1.0–5.7% versus 0.2–0.6%. Currently, there are no generally accepted guidelines for screening for pheochromocytoma and paragangliomas in asymptomatic patients with neurofibromatosis type 1. Case presentation Severe hypertension developed during anesthesia induction in our patient, a 44-year-old Chinese man with neurofibromatosis type 1. We screened for catecholamine level after glioma resection, and the patient was diagnosed with combined pheochromocytoma and paraganglioma. Conclusions A delay in diagnosis or lack of a diagnosis in pheochromocytoma and paraganglioma may increase the perioperative morbidity and mortality risk due to excess catecholamine secretion. Therefore, routine pheochromocytoma and paraganglioma screening preoperatively in patients with neurofibromatosis type 1 is very important.

Pheochromocytomas and Paragangliomas: From Genetic Diversity to Targeted Therapies

Pheochromocytoma and paraganglioma (PCPGs) are rare neuroendocrine tumors that arise from the chromaffin tissue of adrenal medulla and sympathetic ganglia. Although metastatic PCPGs account for only 10% of clinical cases, morbidity and mortality are high because of the uncontrollable mass effect and catecholamine level generated by these tumors. Despite our expanding knowledge of PCPG genetics, the clinical options to effectively suppress PCPG progression remain limited. Several recent translational studies revealed that PCPGs with different molecular subtypes exhibit distinctive oncogenic pathways and spectrum of therapy resistance. This suggests that therapeutics can be adjusted based on the signature molecular and metabolic pathways of PCPGs. In this review, we summarized the latest findings on PCPG genetics, novel therapeutic targets, and perspectives for future personalized medicine.

On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

Abbreviations: AC – acetylcholyne; AF – atrial fibrillation; AP – action potential; BLM – bi-lipid membrane; DPA – Dimethylphenylacetamide; VA – ventricular arrhythmia Introduction: The study aim was to identify essential elements of the antiarrhythmic action mechanism of tertiary and quaternary derivatives of Dimethylphenylacetamide. Materials and Methods: The study was conducted in albino rats and mice of both sexes; isolated neurons of mollusc Limneastagnalis; and strips of rats’ right ventricle myocardium. Two compounds of Dimethylphenylacetamide LKhT-3-00 and LKhT-12-02 were studied. The cholynolytic property of the compounds was investigated by using a Schallek method in the authors’ modification. The adrenotropic activity of the derivatives was explored by Moore and Spear (1984), as well a by the method of catecholamine level detection in heart tissue. The permeability of derivatives through BLM was evaluated experimentally and theoretically. The derivatives’ influence on Na+-current was studied directly and indirectly. Results and Discussion: Neither tertiary nor quaternary derivatives possess the cholynolytic property. LKhT-3-00 prevented an increase in the adrenaline concentration in the left ventricle myocardium. The compounds prevent catecholamine arrhythmia and conductivity disorders. LKhT-3-00 like Lidocaine passes through the BLM of the cardiac cell in an ionised form, whereas the quaternary derivative permeates cardiac cell membrane in an electro-neutral form. Lidocaine derivatives restrain acute ischemia-induced oxidative process growth in the cardiac muscle. Simultaneously, the LKhT-3-00 compound can activate antioxidant mechanisms and prevent acidosis and optimise the balance between [O2] and [CO2] concentrations in coronary dark blood. At a concentration of 10 mg/ml, although the derivatives reduce the amplitude of the leading edge of AP and its rate of increase, they do not, however, affect the duration of AP. Conclusions: The compounds possess the Na+-blocking and cell-protecting properties. They do not affect K+-current through Kv4.3-channels.

Of Mice and Men – or a Lack of Positive Effect of Enhanced Vegetative Nervous System Tonus on Mobilization of Hematopoietic Stem and Progenitor Cells – Results in Patients with Elevated Catecholamine Level in Peripheral Blood Suffering from Acute Psychotic and Anxiety Disorders

Background. It is well known that hematopoietic stem/progenitor cells (HSPCs) circulate under steady-state conditions at detectable levels in peripheral blood (PB), with their numbers increasing in response to stress, inflammation, and tissue and organ injury. Moreover, it has been demonstrated in mice that enhanced tonus of vegetative nervous system regulates mobilization of HSPCs into PB. Moreover, UDP-galactose:ceramide galactosyltransferase-deficient mice, which exhibit aberrant nerve conduction and do not release norepinephrine (NE) into the BM microenvironment, do not mobilize HSPCs in response to G-CSF. However, as recently reported modification of sympathetic output does not affect G-CSF-induced mobilization in humans, as would be predicted. Specifically, normal human HSPC volunteer donors who were receiving NE reuptake inhibitors (NRI) for depression or β2-blockers because of hypertension mobilize in a similar manner as normal controls (Leukemia 2013; 27:24-31). Mobilization in these patients was neither enhanced by NRI administration nor suppressed by β2-blockers, as one would expect based on murine data reported in the literature. Aim of the study. To address this intriguing issue and discrepancy between human and mice, we analyzed levels of circulating HSPCs in patients suffering from acute psychosis and anxiety disorders – clinical situations with elevated level of catecholamine in PB. Namely, these patients are under the influence of several neural mediators, and it is well known that the levels of NE and dopamine are elevated in peripheral tissues and blood. Material and Metods. Enrolled in this study were 30 unrelated individuals with a diagnosis of the first-episode psychosis and 30 patients suffering from acute anxiety disorders. The patients were compared with an ethnic- and gender-matched control group of 35 healthy volunteers without psychiatric disorders, which were excluded according to an examination by a specialist psychiatrist. Patients with a history of serious lifetime medical events, organic brain injuries, or drug/alcohol dependence were excluded from the study. Mobilization of HSPCs was evaluated by i) FACS to enumerate the number of CD34+, CD133+, CD34+CD45+Lin–, and CD133+CD45+Lin– cells circulating in PB, which are enriched for HSPCs, as well as by ii) functional in vitro assays to detect the number of CFU-GM and BFU-E clonogenic progenitors circulating in PB. In parallel we measured level of adrenaline, norepinephrine (NE) and dopamine in PB serum. Both cells and catecholamine levels were enumerated in acute psychotic and anxiety disorders patients before and after treatment and compared with age- and sex-matched controls. Results. We did not observe any significant differences in the numbers of circulating CD34+, CD133+, CD34+CD45+Lin–, and CD133+CD45+Lin– cells as well as clonogenic BFU-E and CFU-GM between normal controls and psychotic patients and patients with anxiety disorders. In particular number of circulating in PB HSPCs was not affected by increased level of adrenaline, norepinephrine and dopamine in PB of patients suffering from acute psychotic syndromes. Conclusions. Our data argue against an effect of enhanced vegetative nervous system tone on the number of HSPCs circulating in PB in humans. Our negative data performed on patients suffering from acute psychoses and anxiety disorders somewhat corroborate data reported for normal HSPC volunteer donors that were previously treated with NRI because of depression or with β2-blockers because of high blood pressure and mobilized with G-CSF (Leukemia 2013; 27:24-31). This finding suggests that there are some clear differences between rodents and humans in the effect of the vegetative nervous system on HSPCs mobilization. Disclosures No relevant conflicts of interest to declare.