Paravertebral Sympathetic Ganglia Research Articles

Dissection of the Sympathetic Nerves Around the Mesorectum at the Abdominopelvic Border.

Introduction Along the border between the abdominal cavity and pelvis are nervous structures that belong to the autonomous nervous system, which is delicate. These can be easily injured during regional surgical procedures such as the total mesorectal excision, where the preservation of the nervous structures should be one of the main objectives. In our study, we aimed to dissect all the sympathetic nerve formations listed at the abdominopelvic border and to present their formation, anatomical routes, and relations, as well as the surgical importance of their preservation. Method We performed anatomical dissections on eight 60- to 75-year-old cadavers (three male and five female) in the Dissection Laboratory of Carol Davila University of Medicine and Pharmacy, Bucharest, ROM. We sectioned each pelvis along the right pararectal line and exposed the hypogastric plexuses and their branches, following their pathways toward the pelvic viscera. Results We highlight the main nervous structures in the pelvis, namely the paravertebral sympathetic ganglion chain, which continues into the pelvis with the sacral ganglion chain, and the prevertebral component of the abdominal sympathetic system, represented by the superior hypogastric plexus and its continuation via the hypogastric nerves toward the inferior hypogastric plexuses. We followed the pathway of the superior hypogastric plexus from its origin down to its bifurcation into the two hypogastric nerves. We then followed the nerves into the pelvis and observed the formation of the inferior hypogastric plexuses, from which branches emerged toward the pelvic organs. Along the way, we point out anatomical landmarks that are crucial in an attempt to spare these nervous structures during regional surgical procedures. Conclusions While performing surgeries such as rectal resection with the excision of the mesorectum, radical hysterectomy, and radical prostatectomy, a thorough knowledge of the sympathetic nerve structures that pass from the abdominal cavity into the pelvis is required to spare pelvic innervation. In such a context, the dissection and anatomical assessment of regional sympathetic nerves can prove to be crucial in establishing operative protocols.

Synchronous ipsilateral adrenal cortical adenoma and ganglioneuroma: A case report

ABSTRACT Synchronous tumors comprising of cortical as well as medullary differentiation are rare in the adrenal gland. Collision tumors comprise of two independent neoplasms arising from the cortex and the medulla without any histological admixture. Adrenal cortico-medullary mixed tumors are rare tumors comprising of adrenal cortical and chromaffin cells intermixed with each other. Ganglioneuroma is a rare benign tumor originating from the paravertebral sympathetic ganglia and is rarely seen in the adrenal medulla. The presence of a synchronous ganglioneuroma with an adrenal cortical adenoma in the ipsilateral adrenal gland is exceedingly rare. We report a collision tumor comprising of an adrenal cortical adenoma and a ganglioneuroma detected as an incidental finding in a pediatric patient who presented with hypertension and palpitations.

Computed tomography-controlled paravertebral sympathectomy in the treatment of obliterating diseases of the arteries of extremities

Surgeries on the paravertebral sympathetic ganglia still keep their meaning. They become surgeries of choice in cases of peripheral arterial damage. Sympathectomy ensures maximum arterial bed dilation, increases blood flow to the ischemic zone, accelerates the angiogenesis. Minimally invasive chemical destruction of the lumbar sympathetic ganglia under the control of a spiral computed tomograph is an alternative to surgical lumbar sympathectomy. It has comparable effectiveness in comparison with open intervention treatment both in the immediate and long-term periods. The study reflects the results of the influence of computed tomographically controlled puncture paravertebral sympathectomy on the symptoms of obliterating diseases of the arteries of lower extremities.

Deconstruction of a hypothalamic astrocyte-white adipocyte sympathetic axis that regulates lipolysis in mice

The role of non-neuronal glial cells in the regulation of adipose sympathetic nerve activity and adipocyte functions such as white adipose tissue lipid lipolysis is poorly understood. Here, we combine chemo/optogenetic manipulations of medio-basal hypothalamic astrocytes, real-time fiber photometry monitoring of white adipose tissue norepinephrine (NE) contents and nerve activities, electrophysiological recordings of local sympathetic inputs to inguinal white adipose tissue (iWAT), and adipose tissue lipid lipolytic assays to define the functional roles of hypothalamic astrocytes in the regulation of iWAT sympathetic outflow and lipolysis. Our results show that astrocyte stimulation elevates iWAT NE contents, excites sympathetic neural inputs and promotes lipolysis. Mechanistically, we find that sympathetic paravertebral ganglia (PG) partake in those astrocyte effects. We also find that astrocyte stimulation excites pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH), and chemogenetic inhibition of POMC neurons blunts the effects induced by astrocyte stimulation. While we cannot exclude potential roles played by other cell populations such as microglia, our findings in this study reveal a central astrocyte-peripheral adipocyte axis modulating sympathetic drive to adipose tissues and adipocyte functions, one that might serve as a target for therapeutic intervention in the treatment of obesity.

Patch-clamp analysis of nicotinic synapses whose strength straddles the firing threshold of rat sympathetic neurons.

Neurons in paravertebral sympathetic ganglia are innervated by converging nicotinic synapses of varying strength. Based upon intracellular recordings of excitatory postsynaptic potentials (EPSPs) with sharp microelectrodes these synapses were classified in the past as either primary (strong) or secondary (weak) by their ability to trigger postsynaptic action potentials. Here we present an analysis of 22 synapses whose strength straddled threshold, thereby distinguishing them from the original classification scheme for primary and secondary synapses. Recordings at 36°C were made from intact superior cervical ganglia isolated from 13 male and 3 female Sprague-Dawley rats and from 4 male spontaneously hypertensive (SHR) rats. Ganglia were pretreated with collagenase to permit patch recording. By dissecting a 1 cm length of the presynaptic cervical sympathetic nerve as part of the preparation and through use of graded presynaptic stimulation it was possible to fractionate synaptic inputs by their distinct latencies and magnitudes, and by the presynaptic stimulus threshold for each component. Comparison of cell-attached extracellular recordings with intracellular recordings of synaptic potentials and synaptic currents indicated that straddling EPSPs are not an artifact of shunting damage caused by intracellular recording. The results also showed that in cells where a single presynaptic shock elicits multiple action potentials, the response is driven by multiple synapses and not by repetitive postsynaptic firing. The conductance of straddling synapses also provides a direct estimate of the threshold synaptic conductance (9.8 nS ± 7.6 nS, n = 22, mean ± SD). The results are discussed in terms of their implications for ganglionic integration and an existing model of synaptic amplification.

Brainstem noradrenergic neurons: Identifying a hub at the intersection of cognition, motility, and skeletal muscle regulation.

Brainstem noradrenergic neuron clusters form a node integrating efferents projecting to distinct areas such as those regulating cognition and skeletal muscle structure and function, and receive dissimilar afferents through established circuits to coordinate organismal responses to internal and environmental challenges. Genetic lineage tracing shows the remarkable heterogeneity of brainstem noradrenergic neurons, which may explain their varied functions. They project to the locus coeruleus, the primary source of noradrenaline in the brain, which supports learning and cognition. They also project to pre-ganglionic neurons, which lie within the spinal cord and form synapses onto post-ganglionic neurons. The synapse between descending brainstem noradrenergic neurons and pre-ganglionic spinal neurons, and these in turn with post-ganglionic noradrenergic neurons located at the paravertebral sympathetic ganglia, support an anatomical hierarchy that regulates skeletal muscle innervation, neuromuscular transmission, and muscle trophism. Whether any noradrenergic neuron subpopulation is more susceptible to damaged protein deposit and death with ageing and neurodegeneration is a relevant question that answer will help us to detect neurodegeneration at an early stage, establish prognosis, and anticipate disease progression. Loss of muscle mass and strength with ageing, termed sarcopenia, may predict impaired cognition with ageing and neurodegeneration and establish an early time to start interventions aimed at reducing central noradrenergic neurons hyperactivity. Complex multidisciplinary approaches, including genetic tracing, specific circuit labelling, optogenetics and chemogenetics, electrophysiology, and single-cell transcriptomics and proteomics, are required to test this hypothesis pre-clinical.

Thoracic ganglioneuroma with extension into the epidural space

A patient in their 30s presented with chronic right upper quadrant abdominal pain, nausea, bloating, and constipation. Her clinical exam was unremarkable, and computed tomography (CT) of the chest and abdomen which showed a large right-sided thoracic mass with extension into the thoracic spinal canal. A needle biopsy revealed a diagnosis of ganglioneuroma, the patient then underwent a combined approach for excision the tumor. Ganglioneuroma is a neuroblastic tumor of a neural crest origin, it originates from paravertebral sympathetic chain ganglia of the posterior mediastinum or retroperitoneum. They usually extend through neuroforamina to involve the epidural space and surgical excision can be curative.

Recurrence of Pheochromocytoma With Metastases After Resection of Primary Tumor

Pheochromocytomas and paragangliomas are rare tumors that arise from the chromaffin cells of the adrenal medulla or sympathetic paravertebral ganglia, respectively. Long-term surveillance is recommended regardless of the thoroughness of surgical resection. Here, we present a patient who was diagnosed with pheochromocytoma who underwent right adrenalectomy and was lost to follow up. She presented 15 years later with recurrence and was found to have multiple metastases. Subsequent genetic testing was also negative.

Metastatic non-functional paraganglioma to the lung

IntroductionParagangliomas are rare endocrine tumors that arise from the extra-adrenal autonomic paraganglia and sympathetic paragangliomas usually secret catecholamines and are located in the sympathetic paravertebral ganglia of thorax, abdomen, and pelvis. In contrast, most parasympathetic paragangliomas are nonfunctional and located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull. Such neoplasms, although rare, are clinically important because they may recur after surgical resection and 10% of them give rise to metastases causing death with the lymphatic nodes, bones, liver, and lungs being the most common locations.Case presentationWe present a case of a 26-year-old male patient that was diagnosed with paraganglioma of the right-frontal lobe infiltrating the falx and frontal bone which was diagnosed after suffering from a headache and abnormal vision. On initial work-up he was found to have right pulmonary nodules that increased in size after follow up and other nodules appeared in the contralateral lung. He underwent subtotal resection of the brain tumor and complete resection of the bilateral pulmonary nodules.ConclusionTo our knowledge, paraganglioma is considered to be a rare entity in the central nervous system with very few cases being reported in the supratentorial region and no cases were reported of metastatic such paraganglioma to the lung.

MON-398 Clinical Case Of Retroperitoneal Paraganglioma

Background: Paraganglioma is a rare neuroendocrine tumor from extra-adrenal chromaffin cells of the sympathetic paravertebral ganglia of thorax, abdomen, and pelvis. In most cases paragangliomas produce catecholamines in large concentrations and the lack of treatment can lead to cardiovascular and cerebral catastrophes [1]. That is why early diagnosis of this tumor is so important and, consequently, knowledge of its diagnostic criterion, too. Clinical case: A 59-year-old man was presented to a cardiologist for rapid increasing of blood pressure (up to 220/120 mmHg), which was accompanied by severe headache and epigastric pain in September 2017. From anamnesis it is known: the disease began suddenly and had paroxysmal flow. The first attack lasted for about 3 minutes and finished itself. Then such attacks occured with different frequency (from 1 per month to several times per week) and were connected with physical activity. The cardiologist suspected diagnosis of pheochromocytoma. The result of urinary fractionated metanephrines measurement showed its levels higher than normal rage but did not confirm suspected diagnosis reliably, so antihypertensive therapy was prescribed to minimize the symptoms. Despite this, the attacks persisted and the patient referred to a surgeon in May 2018. On the basis of patient’s complaints on epigastric pain during the attacks and the neck inflection of the gallbladder revealed by the ultrasound examination, it was decided to carry out cholecystectomy. A week after the operation the patient referred to the endocrinologist because of the continuing attacks. The diagnosis of pheochromocytoma was suspected again, the urinary fractionated metanephrines measurement was repeated, which revealed elevated normetanephrine level (1008 µg/day). A CT of retroperitoneal space revealed a spherical mass sized about 17х16х18 mm in paraaortal region under the left renal vein. The retroperitoneal tumor was removed laparoscopically in August 2018. Pathological examination of the removed mass showed a paraganglioma with uncertain potential of biological behaviour. BP was normal and remained within range without the need of any antihypertensive medication until discharge from hospital. The patient is asymptomatic and normotensive during his follow-up visits. Conclusion: This clinical case shows how a tumor with bright and specific symptoms can be revealed only in several years and after referring to several specialists. Also, this case highlights the importance of knowledge of diagnostic process of different diseases. In the present case the paraganglioma would have been revealed earlier if only the CT of retroperitoneal space had been done just after getting the results of free metanephrines, which were higher than normal.

SAT-318 A Case of Metastatic Paraganglioma

Background: Paraganglioma is a tumor derived from extra-adrenal chromaffin cells of the sympathetic paravertebral ganglia of thorax, abdomen, and pelvis. Malignancy is defined as the presence of metastases in nonchromaffin tissue (1). We discuss a case of metastatic paraganglioma for unusual course of disease and multiple challenges that arose in the management. Case presentation: 51-year-old female with mosaic turner presented to emergency with nausea, vomiting and abdominal pain. She had recent history of episodic high blood pressure and newly diagnosed diabetes mellitus. An abdominal CT scan which was done to assess abdominal pain revealed a retroperitoneal mass suspicious for paraganglioma. Subsequent blood work showed high plasma normetanephrine (x7 upper limit of normal). She underwent surgical resection of intra abdominal mass after blood pressure control with adequate alfa blockade treatment. Surgical pathology result confirmed the diagnosis of paraganglioma and showed high Ki-67 level and mitoses count. Three months post surgery, she developed severe blood pressure difficult to control; and her blood work revealed high plasma and urine normetanephrine suggestive of paraganglioma recurrence. The pre-op imaging including CT chest and abdomen were negative for any evidence of malignancy. However, repeat imaging three months post surgery showed multiple bone lesion in the skull, sternum, spine, and pelvic suggestive of metastatic disease. One week after the diagnosis of metastatic disease, she developed acute onset right eye proptosis due to retro-orbital mass which was resected. Surgical pathology was positive for metastatic paraganglioma. To determine extent of the disease and therapeutic choice, an octreotide scan was done which showed mild octreotide uptake in bone lesions. Therefore, peptide receptor radionucleotide radiation treatment (PRRT) was not considered for her metastatic disease treatment. In consultation with medical oncology, systemic chemotherapy was suggested, but it was also declined given her poor functional status. Eventually, she was started on targeted molecular therapy with sunitinib with good tolerance and response. We report this patient, first for the unusual course of disease given progression of metastatic disease over three months after surgical resection; second for the challenging therapeutic decision given the patient and disease unique characteristics. Conclusion: This case demonstrates an aggressive course of metastatic paraganglioma disease over a short period of time following surgical resection of primary tumor mass which shows the importance of earlier follow up post surgical resection of paraganglioma. This case might also justify broader work up such as MIBG or octreotide scan to determine the extent of disease and plan for the best therapeutic approach in certain cases prior to surgery.

SAT-312 A Rare Case of Metastatic Paraganglioma with Positive SDHB Mutation: An Incidentally Found Silent Monster

Introduction: Although paragangliomas (PG) are derived from extra-adrenal chromaffin cells of sympathetic paravertebral ganglia in the thorax, abdomen, and pelvis, they can also arise from parasympathetic ganglia located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull. Non-secretory PG have a low prevalence, are often silent, and can present as a malignant tumor with mass effects. Symptoms often include: unilateral hearing loss, pulsatile tinnitus, cough, hoarseness, pharyngeal fullness, swallowing difficulty, pain, and/or problems with tongue motion. Case: A 25 year old African American woman presented with 2 yrs of exertional presyncope, night sweats, subjective fevers, 20 lb. weight loss and a nontender enlarging left neck mass. Family history: Mother had thyroid cancer. Physical exam- BMI 21 kg/m2, BP 118/72 mmHg, HR 74, with indurated, fixed, nontender mass in left upper neck, inferior to mandibular angle. Laboratory-Hgb 6.9 g/dl, MCV 71.7, Iron 137 mcg/dl, TIBC 151 mcg/dl, Ferritin 155 ng/ml, CRP 65.20 mg/dl, ESR 122 mm/hr, AST 107 U/l, ALT 7 U/L, Alk Phos 81 U/l. EGD and Colonoscopy-normal. CT scan of neck, abdomen and pelvis: 6.0x3.5x2.7 cm heterogeneously enhancing mass in left neck involving skull base at carotid canal level, within the internal carotid space, causing external compression of left internal jugular vein, with multiple hypervascular lesions in bilateral lungs, liver and spleen, as well as cervical, thoracic, lumbar and sacral spine. Packed red blood cells were transfused. Liver Biopsy-metastatic paraganglioma with SDHB mutation. Laboratory tests- normal plasma catecholamines, thyroid function tests, prolactin, cortisol, ACTH, LH, FSH. A few weeks later, she reported new onset left sided tinnitus, orbital pain and vision changes. MRI Brain/orbit- 10 x 11 mm enhancing lesion centered in left cavernous sinus near orbital apex without intra or extraconal lesion. Chemotherapy was started with vincristine, cyclophosphamide and dacarbazine. After 12 weeks of chemotherapy, the left neck mass size decreased, tinnitus, and vision changes resolved. She was referred for genetic counseling and multidisciplinary care. Discussion: Our patient had malignant head and neck PG with SDHB mutation. Mutations in the gene encoding SDH subunit B (SDHB) can lead to metastatic disease in ≥ 40% of patients, are frequently familial, and are associated with other malignancies (renal cell carcinoma, pituitary adenoma, breast and thyroid cancer). Although there are current guidelines regarding diagnosis and management of non-malignant secretory paraganglioma/pheochromocytoma, screening and management of metastatic disease is not clear. Therefore, it is important to have a low threshold of suspicion for early diagnosis. Provider awareness and education regarding diagnosis and management is needed.

Heme Oxygenase Inhibition Sensitizes Neuroblastoma Cells to Carfilzomib.

Neuroblastoma (NB) is an embryonic malignancy affecting the physiological development of adrenal medulla and paravertebral sympathetic ganglia in early infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a possible pharmacological treatment for solid tumors including NB. In the present study, we tested the effect of a novel non-competitive inhibitor of heme oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene expression (about 18-fold) and HO activity (about 8-fold), following activation of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity was further confirmed by the protective effect of pharmacological induction of HO-1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion, our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 / 71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER stress activation. These results suggest that PIs may represent a possible pharmacological treatment for solid tumors and that HO-1 inhibition may represent a possible strategy to overcome chemoresistance and increase the efficacy of chemotherapic regimens.

Autonomic Regulation and Ventricular Arrhythmias.

Autonomic nervous system (ANS) has a crucial role of regulating cardiac function in the physiological state and contributes to the pathogenesis of arrhythmias in the diseased state. The cardiac neuraxis consists of multiple feedback loops consisting of efferent and afferent limbs, mediating neurotransmission to and from the heart. Efferent parasympathetic neurotransmission is mediated by the vagus nerve, while paravertebral sympathetic ganglia relay efferent sympathetic neurotransmission to the heart. The association between autonomic activity and ventricular arrhythmias (VAs) has been studied extensively in both experimental models and humans. Efferent parasympathetic activity is felt to be antiarrhythmic, while the activation of efferent sympathetic signals is proarrhythmic. The cardiac neuraxis undergoes remodeling and becomes dysfunctional in the setting of myocardial infarction (MI), chronic cardiomyopathy (CMY), and structural heat disease. Altered ANS function has been shown to initiate and/or maintain VAs via various mechanisms. Interventions targeting the ANS have been used clinically to treat VAs, particularly in patients with hereditary heart rhythm disorders and structurally abnormal hearts. Clinical applications of cardiac neuraxial modulation at the level of spinal cord, stellate ganglion, and peripheral sympathetic and vagus nerve are being developed. In this review, the anatomy of cardiac autonomic innervation, the association between autonomic activity and ventricular arrhythmogenesis, and clinical applications of neuraxial modulation in the treatment of VAs are discussed.

Origin and initiation mechanisms of neuroblastoma.

Neuroblastoma is an embryonal malignancy that affects normal development of the adrenal medulla and paravertebral sympathetic ganglia in early childhood. Extensive studies have revealed the molecular characteristics of human neuroblastomas, including abnormalities at genome, epigenome and transcriptome levels. However, neuroblastoma initiation mechanisms and even its origin are long-standing mysteries. In this review article, we summarize the current knowledge about normal development of putative neuroblastoma sources, namely sympathoadrenal lineage of neural crest cells and Schwann cell precursors that were recently identified as the source of adrenal chromaffin cells. A plausible origin of enigmatic stage 4S neuroblastoma is also discussed. With regard to the initiation mechanisms, we review genetic abnormalities in neuroblastomas and their possible association to initiation mechanisms. We also summarize evidences of neuroblastoma initiation observed in genetically engineered animal models, in which epigenetic alterations were involved, including transcriptomic upregulation by N-Myc and downregulation by polycomb repressive complex 2. Finally, several in vitro experimental methods are proposed that hopefully will accelerate our comprehension of neuroblastoma initiation. Thus, this review summarizes the state-of-the-art knowledge about the mechanisms of neuroblastoma initiation, which is critical for developing new strategies to cure children with neuroblastoma.

Lack of pathogenic potential of peripheral \u03b1-synuclein aggregates from Parkinson\u2019s disease patients

In Parkinson’s disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been speculated they may progressively spread to the central nervous system through synaptically-connected brain networks and reach the substantia nigra to trigger herein dopaminergic dysfunction/degeneration and subsequent parkinsonism. Supporting a pathogenic role for α-synuclein aggregates we have previously shown that LB purified from postmortem PD brains promote α-synuclein pathology and dopaminergic neurodegeneration when intracerebrally inoculated into wild-type mice. However, the pathogenic capacity of PD-derived peripheral α-synuclein aggregates remains unknown. Here we addressed this question using purified LB-type α-synuclein aggregates from postmortem PD stellate ganglia (SG), a paravertebral sympathetic ganglion that exhibits consistent and conspicuous Lewy pathology in all PD patients. In contrast to our previous findings using nigral LB extracts, intracerebral inoculation of SG-derived LB into mice did not trigger long-term nigrostriatal neurodegeneration nor α-synuclein pathology. The differential pathogenic capacities of central- and peripheral-derived α-synuclein aggregates appear independent of the absolute amount and basic biochemical properties of α-synuclein within these aggregates and may rely instead on differences in α-synuclein conformation and/or yet unrecognized brain region-specific intrinsic factors. Our results argue against a putative pathogenic capacity of peripheral α-synuclein aggregates to promote α-synuclein pathology in the brain, propagate between neuronal networks or induce neurodegeneration.

Differential Distribution of Renal Nerves in the Sympathetic Ganglia of the Rat.

The renal nerve plexus comprises efferent and afferent fibers. It controls urine production and bodily fluid homeostasis. Efferent fibers to the kidney include sympathetic nerve fibers from their main ganglia, the prevertebral suprarenal ganglia (SrG), and the paravertebral sympathetic chain ganglia (ChG). In the present study, we examined topological innervation from these ganglia to the renal parenchymal segments of the left kidney of the rat. Fluoro-Gold was injected into the rostral or caudal poles of the left kidney. Approximately 50% of the cells in the SrG of rats injected in the rostral pole were labeled, while 60% of the cells in the ChG T13 of rats injected in the caudal pole were labeled. In addition, we performed dual-probe retrograde tracing of the nerves using two kinds of fluorescent-conjugated cholera toxins (f-CTbs) injected into the rostral and caudal poles of the left kidney. The cells labeled with each f-CTb were distributed differently in the left SrG and the lower ChGs; no dual-labeled cells were found in these ganglia. Anterograde tracing with pCAGGS-tdTomato vector transfected into the left SrG showed that tdTomato-labeled nerve varicosities extended to the cortical arterioles and urinary tubules. Immunohistochemistry revealed that they were positive to tyrosine hydroxylase and synaptophysin, suggesting that they possessed sympathetic nerve endings. Our results show that renal efferent nerves in the SrG may control the rostral part of the kidney and innervate the multiple effectors in the cortex. Anat Rec, 300:2263-2272, 2017. © 2017 Wiley Periodicals, Inc.

Video-Assisted Thoracoscopic Removal of a Paraspinal Neuroblastoma Presenting as a Parotid Mass

Introduction: Neuroblastoma is the most common extracranial cancer in childhood. Paravertebral neuroblastomas arise from the paravertebral sympathetic ganglia. The cancer metastasizes through both lymphatic and hematogenous routes to bone, skin, and liver. The video demonstrates an atypical presentation of a paraspinal neuroblastoma with surgical resection of the primary paraspinal lesion. Materials and Methods: The patient presented with increased swelling over the right mandible for 2 weeks despite antibiotic treatment for presumed parotitis. Preoperative computed tomography (CT) imaging of the mass revealed a lytic lesion. CT-guided fine needle aspiration revealed neuroblastoma. CT of head/chest/abdomen/pelvis was performed for staging that revealed a left paraspinal mass measuring 2.5 × 3.0 × 1.3 cm adjacent to T10–T11. A bone scan and metaiodobenzylguanidine (MIBG) scan showed metastatic disease consistent with Stage IV neuroblastoma. After four cycles of chemotherapy, the patient had a >50% reduction in the primary paraspinal lesion. Video-assisted thoracoscopic surgery (VATS) was performed. The mass and accompanying lymph node were excised without complication. Results and Conclusion: Final pathology demonstrated a 1.5 × 1.2 × 0.8 cm neuroblastic tumor with treatment effect with involvement of the margin. The accompanying lymph node was negative for tumor involvement. The patient underwent subsequent chemotherapy under the guidance of pediatric oncology. Repeat CT, bone scan, and MIBG scan at 1-year follow-up were negative for disease recurrence. Parotid metastases of neuroblastoma are rare with fewer than five case reports have been published in the past several decades.1 Common causes of parotid masses include salivary gland tumors and parotitis. Typically, metastatic disease in the parotid gland arises from nearby head and neck neoplasms. For a practicing clinician, it is important to keep in mind this rare entity when apparent parotitis does not respond to conventional antibiotic treatment. For Stage IV neuroblastoma, chemotherapy and immunomodulatory therapy are critical. Surgical resection is attempted with the goal of removal of the entire tumor and histologic staging; however, negative microscopic tumor margins are not necessary.2 Currently, open thoracotomy has been the standard procedure for thoracic disease in children, whereas VATS has remained controversial.3 However, recently, VATS for neurogenic tumors has shown to give good results with minimal postoperative complications. Major advantages include avoidance of open thoracotomy complications and enhanced surgical visualization.4 Several other advantages include decreased morbidity and duration of hospital stay. The case presented demonstrates an atypical presentation of paraspinal neuroblastoma with metastasis to the parotid gland. VATS procedure was used for removal of the primary paraspinal mass. This case shows that the VATS procedure is a safe and effective method of surgery for thoracic masses in children. No competing financial interests exist. Runtime of video: 5 mins 29 secs

Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor.

Pituitary adenylate cyclase-activating polypeptide (PACAP, encoded by adcyap1) plays an important role in ectodermal development. However, the involvement of PACAP in the development of other germ layers is still unclear. This study assessed the expression of a PACAP-specific receptor (PAC1) gene and protein in mouse bone marrow (BM). Cells strongly expressing PAC1+ were large in size, had oval nuclei, and merged with CD34+ cells, suggesting that the former were hematopoietic progenitor cells (HPCs). Compared with wild-type mice, adcyap1−/− mice exhibited lower multiple potential progenitor cell populations and cell frequency in the S-phase of the cell cycle. Exogenous PACAP38 significantly increased the numbers of colony forming unit-granulocyte/macrophage progenitor cells (CFU-GM) with two peaks in semi-solid culture. PACAP also increased the expression of cyclinD1 and Ki67 mRNAs. These increases were completely and partially inhibited by the PACAP receptor antagonists, PACAP6-38 and VIP6-28, respectively. Little or no adcyap1 was expressed in BM and the number of CFU-GM colonies was similar in adcyap1−/− and wild-type mice. However, PACAP mRNA and protein were expressed in paravertebral sympathetic ganglia, which innervate tibial BM, and in the sympathetic fibers of BM cavity. These results suggested that sympathetic nerve innervation may be responsible for PACAP-regulated hematopoiesis in BM, mainly via PAC1.

Targeted stellate decentralization: Implications for sympathetic control of ventricular electrophysiology

Selective bilateral cervicothoracic sympathectomy has proven to be effective for managing ventricular arrhythmias in the setting of structural heart disease. In the procedure currently used, the caudal portions of both stellate ganglia along with thoracic chain ganglia down to T4 ganglia are removed. The purpose of this study was to define the relative contributions of the T1-T2 and T3-T4 paravertebral ganglia in modulating ventricular electrical function. In anesthetized vagotomized porcine subjects (n = 8), the heart was exposed via sternotomy along with right and left paravertebral sympathetic ganglia to the T4 level. A 56-electrode epicardial sock was placed over both ventricles to assess epicardial activation-recovery intervals (ARIs) in response to individually stimulating right and left stellate vs T3 paravertebral ganglia. Responses to T3 stimuli were repeated after surgical removal of the caudal portions of stellate ganglia and T2 bilaterally. In intact preparations, stellate ganglion vs T3 stimuli (4 Hz, 4-ms duration) were titrated to produce equivalent decreases in global ventricular ARIs (right side: 85 ± 6 ms vs 55 ± 10 ms; left side: 24 ± 3 ms vs 17 ± 7 ms). Threshold of stimulus intensity applied to T3 ganglia to achieve threshold was 3 times that of T1 threshold. ARIs in unstimulated states were unaffected by bilateral stellate-T2 ganglion removal. After acute decentralization, T3 stimulation failed to change ARIs. Preganglionic sympathetic efferents arising from the T1-T4 spinal cord that project to the heart transit through stellate ganglia via the paravertebral chain. Thus, T1-T2 surgical excision is sufficient to functionally interrupt central control of peripheral sympathetic efferent activity.