Anesthesia Management in Hereditary Pheochromocytoma and Paraganglioma:Updated Insights into Clinical Features and Perioperative Care

Approximately 40% of pheochromocytoma and paraganglioma(PPGL) cases are familial, typically presenting earlier with more complex symptoms. This paper synthesizes literature and guidelines to inform on clinical characteristics and perioperative care for PPGL. Pheochromocytoma in von Hippel-Lindau(VHL) disease exhibits heightened secretion activity without significant perioperative hemodynamic changes. Tumors in multiple endocrine neoplasia type 2(MEN2) have a stronger endocrine function, which may induce hemodynamic fluctuations during surgery. Therefore, pheochromocytoma screening is essential at all stages of MEN2. Neurofibromatosis type 1(NF1) often presents multisystem lesions and can result in difficult airway. Pheochromocytoma should be evaluated when NF1 patients present hypertension. Pheochromocytoma and paraganglioma type 5 may present multiple lesions of pheochromocytoma or paraganglioma. In summary, hereditary PPGLs may present with severe lesions in other systems, beyond tumor function. A multi-disciplinary team(MDT) approach is often invaluable in perioperative management.

Utilizing bioinformatics for integrated analysis of multiple genes in the diagnosis and pathogenesis of metastatic pheochromocytoma and paraganglioma

Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.

Extrasurrenal Pheochromocytoma: A Case Report and Review of the Literature

Introduction: Pheochromocytoma is a rare cause of endocrine hypertension. We report the case of an extra-adrenal pheochromocytoma discovered in the setting of an abdominal mass. Observation: The patient was 25-year-old and presented with headaches, excessive sweating and palpitations, followed by a sensation of abdominal weightlessness and diastolic arterial hypertension. Abdominal computed tomography revealed a retroperitoneal, right para-renal extra-adrenal mass. In biology, an increase in urinary methoxylated derivatives at the expense of normetanephrine. Conclusion: Pheochromocytoma is a rare disease, diagnosed by measuring urinary or plasma methoxylated derivatives. Conventional or nuclear imaging allows topographic diagnosis. Genetic studies helps to identify other tumors.

Case Report:Diagnosis and treatment of pheochromocytoma in urinary bladder

Objective： To study the diagnosis and treatment ofpheochromocytoma in urinary bladder. Methods： Six cases of bladder pheochromocytoma were studied. Four cases showed hypertension, 3 of which were paroxysmal hypertension during urination. Catecholamine （CA） was increased in a case, and vanillymandelic acid （VMA） was increased in 2 cases. Bladder submucosal mass was detected by B-ultrasound in 5 cases （5/5）, computerized tomography （CT） in 3 cases （3/3）, cystoscopy in 5 cases （5/6）. Four cases took a-receptor blocker for 2 weeks, 1 case took β-receptor blocker to decrease heart rate. All patients were treated with surgical operation including 4 partial cystectomies, 2 excavations. Results： Three cases had manifestations including headache, excessive perspiration and hypertension during cystoscopy. Four cases were confirmed before operation. Two cases showed hypertension during operation. All patients were pathologically diagnosed as pheochromocytoma post- operatively. In five cases followed up, blood pressure returned to normal. No patient had relapse and malignancy. Conclusions： Typical hypertension during urination comprised the main symptoms. We should highly suspect bladder pheochromocytoma if a submucosal mass was discovered with B-ultrasound, CT, ^131I-M1BG （methyliodobenzylguanidine） and cystoscopy. The determination of CA in urine is valuable for qualitative diagnosis. The preoperative management of controlling blood pressure and expansion of the blood volume are very important. Surgical operation is a good method for effective treatment. Postoperative long-time followed up is necessary.

Multiple gastrointestinal stromal tumors and bilateral pheochromocytoma in neurofibromatosis

The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively. After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors. Discussion includes review of the literature.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia(paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome(ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma(MTC).

CLINICAL DIAGNOSIS AND TREATMENT OF NONFUNCTIONING PHEOCHROMOCYTOMAS IN 14 PATIENTS

Objective To analyze the clinical characteristics of nonfunctioning pheochromocytoma, and to evaluate the efficacy of 131I-metaiodobenzylguanidine (MIBG) scan in the diagnosis and perioperative treatment of nonfunctioning pheochromocy- toma. Methods The clinical data of 14 patients with nonfunctioning pheochromocytoma were analyzed retrospectively. Plasma free corticoid, renin, aldosterone, and urine catecholamines levels were estimated. B-mode ultrasonography, computed tomo- graphy scan, thoracic X-ray and 131I-MIBG were used. Results All patients with nonfunctioning pheochromocytoma had no hypertension and the tumors were found inciden- tally. The 24 hours urine catecholamines levels in 80% (8/10) patients were normal. The positive rate of 131I-MIBG was 80% (8/10) and the specificity was 100%. All patients underwent surgical operation of tumor resection. No preoperative volume expansion was given to all patients. All tumors were resected completely, and no death accident happened. There was no recurrence and metastasis after operation by long-term follow-up. Conclusion 131I-MIBG scan is the first choice technique for the diagnosis of nonfunctioning pheochromocytoma. Blood volume expansion is unnecessary before resection of pheochromocytoma.no recurrence and metastasis})

Bilateral Pheochromocytoma as First Presentation of von Hippel-Lindau Disease in a Chinese Family

Objective To investigate the clinical and genetic features of a Chinese family with yon Hippel- Lindau （VHL） disease revealed by bilateral pheochromocytoma. Methods The proband and other members in a Chinese family with familial pheochromocytoma were clinically evaluated and followed up. Genomic DNA extracted from the peripheral blood of 8 family members （including 3 patients） was amplified by polymerase chain reaction （PCR） and the PCR products were directly sequenced. Results The first presentation in the proband, his mother, and his sister was bilateral pheochromocytoma, and the missense mutation of 695G-A （Arg161Gln） in exon 3 of VHL gene was detected in the three patients. In the follow-up study, the proband and his mother were found to have other VHL tumors, induding retinal and cerebellar hemangioblastomas and pancreatic tumor. Neither clinical presentation of VHL disease nor gene mutation was found in other family members. Conclusion VHL disease should be suspected in some patients with familial pheochromocytoma, and VHL gene screening helps to achieve early diagnosis of the disease.

Anesthetic management of bilateral pheochromocytoma resection in Von Hippel-Lindau syndrome:A case report

BACKGROUND Von Hippel-Lindau disease(also known as VHL syndrome),is an autosomal dominant inherited disease.We describe a sporadic case of VHL syndrome where bilateral pheochromocytomas were unexpectedly identified.The patient underwent selective laparoscopic resections of the pheochromocytomas,and the anesthetic management during surgery was complex and challenging.CASE SUMMARY A 22-year-old man presented to our hospital to seek medical advice for infertility without any other complaints.The results of computed tomography and catecholamine levels in blood and urine demonstrated adrenal gland masses which were diagnosed as pheochromocytomas.Further examination confirmed that the patient also had VHL syndrome.After thorough preparation,the patient underwent selective laparoscopic resection of the pheochromocytomas and was discharged 10 d after surgery.We describe the process of perioperative anesthesia management in this patient undergoing pheochromocytoma resection.CONCLUSION This case summaries specific clinical traits and considerations in perioperative anesthesia management for VHL syndrome patients undergoing bilateral pheochromocytoma resection.

Octreotide reverses shock due to vasoactive intestinal peptide-secreting adrenal pheochromocytoma: A case report and review of literature

Vasoactive intestinal peptide-producing tumors （VIP-oma） usually originate in the pancreas and are chara-cterized by diarrhea, hypokalemia, and achlorhydria （WDHA syndrome）. In adults, nonpancreatic VIPoma is very rare. Herein, we report an unusual case of VIP-producing pheochromocytoma marked by persistent shock, fushing, and watery diarrhea and high sensitivity to octreotide. A 53-year-old woman was hospitalized for sudden-onset hypertension with convulsions, which then rapidly evolved to persistent shock, fushing, and watery diarrhea. Abdominal computed tomography indicated a left adrenal mass, accompanied by bleeding;and marked elevations of both plasma catecholamine and VIP concentrations were documented via laboratory testing. Surprisingly, all clinical symptoms responded swiftly to octreotide treatment. Once surgically treated, hormonal levels normalized in this patient, and the clinical symptoms dissipated. Postoperative pathological and immunohistopathological studies confrmed a VIP-secreting pheochromocytoma with strong, diffuse positivity for somatostatin receptor type 2. During a 6-mo follow-up period, she seemed in good health andwas symptom-free.

Management of bladder pheochromocytoma by transurethral resection

Bladder pheochromocytoma is the most common extra-adrenal genitourinary tumor.Endoscopic management is feared due to the risk of intra-operative hypertensive crisis.We described a case of successful endoscopic management of a bladder pheochromocytoma and discussed its technical aspects.

Pheochromocytoma and stress cardiomyopathy:Insight into pathogenesis

AIM To investigate the occurrence of cardiomyopathy(CMP)in a cohort of patients with histologically proven pheochromocytoma(pheo),and to determine if catecholamine excess was causative of the left ventricular(LV)dysfunction.METHODS A retrospective chart review spanning years 1998through 2014 was undertaken and patients with a diagnosis of pheo confirmed with histopathologic examination were included.Presenting electrocardiograms and cardiac imaging studies were reviewed.Transthoracic echocardiography(TTE),ventriculography or single positron emission computed tomography imaging was evaluated and if significant abnormalities[left ventricular hypertrophy(LVH)or LV dysfunction]were noted in the pre operative period a follow up post-operative study was also analyzed.Multivariate analysis using logistic regression was used to investigate independent predictors for outcomes of interest,LV dysfunction and LVH.RESULTS We identified 18 patients with diagnosis of pheo confirmed on pathology.Mean age was 54.3±19.3years and 11(61.1%)patients were females.50%of such patients had either resistant hypertension or labile blood pressures during hospitalization,which had raised suspicion for a pheo.Cardiac imaging studies were available for 12(66.7%)patients at the time of inclusion into study and preceding the adrenalectomy.7(58.3%)patients with a TTE available for review had mild or more severe LVH while 3(25%)patients had LV dysfunction of presumably acute onset.In a multivariate analysis,elevated catecholamine levels as assessed by urinary excretion of metabolites was not an independent predictor of development of LV systolic dysfunction or of presence of LVH on TTE.Two female patients with a preceding history of hypertension had marked LV hypertrophy and systolic anterior motion of the mitral valve.Prolongation of the QTc interval was noted in 5(27.8%)patients but no acute arrhythmias were observed in any patient.CONCLUSION This study adds to the growing body of literature on the predilection of patients with pheochromocytomas to develop non-ischemic CMP.Degree of catecholamine excess as measured by urinary secretion of metabolites did not predict the development of CMP but 2 of 3patients developed CMP in the setting of significant acute physiologic stress.Our findings provide support to the proposed etiologic role of elevated catecholamines in TC and other stress induced forms of CMP,however,activation of a brain-neural-cardiac axis from acute stress and local release of catecholamines but not chronic catecholamine elevations are likely to be responsible in pheo related CMP.

Watery diarrhea,hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma

Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma, which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review.

Pheochromocytoma with abdominal aortic aneurysm presenting as recurrent dyspnea,hemoptysis,and hypotension:A case report

BACKGROUND Pheochromocytomas are rare endocrine tumors with various clinical manifestations,and few of them might present with profound,life-threatening conditions.CASE SUMMARY We report the case of a 65-year-old man who complained of sudden dyspnea and hemoptysis for half a day.There was no obvious cause for the patient to have dyspnea,coughing,or coughing up to approximately 100 mL of fresh blood.Finally,he was diagnosed with pheochromocytoma crisis(PCC),coexisting with an abdominal aortic aneurysm(AAA).CONCLUSION We report a case of pheochromocytoma presenting with recurrent hemoptysis,dyspnea and hypotension coexisting with an AAA.It not only proved the uncommon manifestations of pheochromocytoma but also directed clinicians to consider PCC among the possible diagnoses when meeting similar cases.Moreover,surgical excision is the most beneficial method for the treatment of pheochromocytoma coexisting with AAA when the situation is stable.

Pheochromocytoma with delayed tumor thrombus detection in renal vein: A case report

BACKGROUND Pheochromocytomas with inferior vena cava(IVC)or renal vein tumor thrombus are rare.Surgical management is the first choice.CASE SUMMARY We presented a 42-year-old man with adrenal pheochromocytoma and delayed tumor thrombus detection in the renal vein at the entrance of the IVC three months after adrenalectomy.We performed laparoscopic adrenalectomy during the first surgery and robot-assisted laparoscopic nephrectomy and resection of tumor thrombus during the second surgery.CONCLUSION We report the surgical management of a patient with adrenal pheochromocytoma with tumor thrombus at the entrance of the IVC.Robot-assisted laparoscopic surgery is safe and efficient.

Robot-Assisted Laparoscopic Resection of Large-Volume Pheochromocytoma through the Surface of the Kidney

Objective: To investigate the clinical application of robot-assisted laparoscopic surgery on the treatment of large-volume pheochromocytoma. Methods: A retrospective analysis of 31 patients with pheochromocytoma disease admitted to the Department of Urology, Affiliated Hospital of Hebei University from May 2020 to August 2021. According to clinical data, the tumor volume was 62.4 ± 29.5 mm, including 16 males and 15 females, aged (35.6 ± 16.1) years old;17 cases on the left side and 14 cases on the right side. All patients underwent anatomical resection through the renal superficial approach, and underwent pheochromocytoma resection through the retroperitoneal approach. The operation time, blood loss, postoperative complications, retention time of drainage tube and postoperative follow-up were observed. Results: All the 31 operations were successful, and there were no obvious postoperative complications. The average operation time, blood loss, and drainage tube retention time were 71 min, 80 mL, and (1.2 ± 0.6) days, respectively. Postoperative pathology was confirmed to be pheochromocytoma. There was no tumor recurrence in the follow-up for 1 - 15 months. Conclusion: Robot-assisted laparoscopic anatomical resection of large-volume pheochromocytoma through the renal surface of the abdominal cavity can provide a larger operating space during the operation, with clear anatomical landmarks of “lipocrasis”, less bleeding, less trauma, intraoperative and postoperative. The advantages of fewer complications, procedural operation, and shorter learning curve can be promoted in clinical practice.

Multivessel coronary artery ectasia and severe calcification in a patient with pheochromocytoma:a case report

Multivessel coronary artery ectasia with severe calcification is rare among patients with coronary artery disease. A 74-year-old Chinese woman suffered from acute myocardial infarction on a background of 50 years of poorly controlled hypertension secondary to pheochromocytoma, which was surgically removed in June 2012 prior to the presentation. Coronary angiography revealed total occlusion of the proximal left anterior descending artery, and multiple ectasias with severe calcification in the left main, circumflex and right coronary artery. After an aspiration thrombectomy and balloon angioplasty, grade 3 coronary flow was restored in the left descending coronary artery. No cardiac events were found in the 12-month follow-up. We conclude that multivessel coronary artery ectasia and severe calcification may be present in patients with a long-standing history of hypertension secondary to pheochromocytoma.

Malignant pheochromocytoma:Hepatectomy for liver metastases

Malignant pheochromocytoma accounts for approximately 10% of pheochromocytoma cases. The main site of distant metastasis is the liver. Hypertensive crisis due to catecholamine oversecretion is potentially fatal. We present a case of malignant pheochromocytoma with multiple liver metastases. A 60-year-old female with repeated hypertensive episodes was diagnosed with malignant pheochromocytoma. She underwent a left adrenalectomy and partial hepatectomy with resection of segment 6. Catecholamine levels remained high after surgery and she received repeated cycles of chemotherapy. Four months after surgery, multiple liver metastases were detected. In spite of ongoing chemotherapy, catecholamine levels eventually became uncontrollable. Serum and urine noradrenaline andvanillylmandelic acid levels increased, but adrenaline and dopamine levels stayed within the normal range. Preoperative liver imaging revealed multiple metastases in all segments except segment 4. Percutaneous transhepatic portal vein embolization(PTPE) of the right and lateral branches of the portal vein was performed. The functional liver volume of segment 4 increased after PTPE. Right hepatectomy, lateral segmentectomy and partial resection of segment 1 were performed 10 mo after the initial surgery. Intraoperative ultrasonography detected two small tumors in segment 4, which were treated with intraoperative microwave coagulation therapy. Noradrenaline levels normalized immediately after the second hepatectomy. As there was increased telomerase activity in the resected specimen, she received adjuvant chemotherapy. She remained in good health for 2 years. However, further metastases eventually occurred and she subsequently died due to a brain hemorrhage. Hepatectomy may be a therapeutic option for reduction of tumor mass in pheochromocytoma with liver metastases.

Adenovirus-mediated short hairpin RNA interference against p75 neurotrophin receptor in pheochromocytoma cells

Previous studies have confirmed that motor neuron apoptosis in the anterior horn of the lumbosacral spinal cord is positively correlated with p75 neurotrophin receptor （p75NTR） expression in rat models of cauda equina syndrome. This study used adenovirus to carry a short hairpin RNA （shRNA） for p75NTR gene silencing, to reduce p75NTR expression in the damaged phase and to decrease motor neuron apoptosis. Three p75 siRNA template oligonucleotide segments （shRNA） were designed, and cloned into the 1.0 CMV shuttle vector. HEK293 cells were cotransfected with shuttle vector （carrying shRNA） and an adenovirus vector framework expressing enhanced green fluorescent protein. Thus, this study successfully obtained adenovirus carrying p75shRNA. The obtained viruses were named Ad.shRNA1, Ad.shRNA2, and Ad.shRNA3. The recombinant adenoviruses were separately used to infect cultured pheochromocytoma cells （PC12）. Forty-eight hours later, p75NTR mRNA and total protein were analyzed from the PC12 cells. Compared with the negative controls, RNA interference rates were separately 98.49 ± 0.68%, 95.08 ± 1.79% and 96.60 ± 1.14% at the mRNA level, and 72.89 ± 2.17%, 58.83 ± 1.15% and 59.88 ± 0.44% at the protein level in the Ad.shRNA1, Ad.shRNA2, and Ad.shRNA3 groups, respectively. Thus, recombinant adenovirus shRNA-mediated gene silencing successfully suppressed p75NTR expression.