Single-cell transcriptome analysis reveals tumoral microenvironment heterogenicity and hypervascularization in human carotid body tumor.

Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high vascularization and abnormal proliferation. However, single-cell transcriptome analysis of the microenvironment composition and molecular complexity in CBT has yet to be performed. In this study, we performed single-cell RNA sequencing (scRNA-seq) analysis on human CBT to define the cells that contribute to hypervascularization and chronic hyperplasia. Unbiased clustering analysis of transcriptional profiles identified 16 distinct cell populations including endothelial cells (ECs), smooth muscle cells (SMCs), neuron cells, macrophage cells, neutrophil cells, and T cells. Within the ECs population, we defined subsets with angiogenic capacity plus clear signs of later endothelial progenitor cells (EPCs) to normal ECs. Two populations of macrophages were detectable in CBT, macrophage1 showed enrichment in hypoxia-inducible factor-1 (HIF-1) and as well as an early EPCs cell-like population expressing CD14 and vascular endothelial growth factor. In addition to HIF-1-related transcriptional protein expression, macrophages1 also display a neovasculogenesis-promoting phenotype. SMCs included three populations showing platelet-derived growth factor receptor beta and vimentin expression, indicative of a cancer-associated fibroblast phenotype. Finally, we identified three types of neuronal cells, including chief cells and sustentacular cells, and elucidated their distinct roles in the pathogenesis of CBT and abnormal proliferation of tumors. Overall, our study provided the first comprehensive characterization of the transcriptional landscape of CBT at scRNA-seq profiles, providing novel insights into the mechanisms underlying its formation.

Prevalence, characteristics, evaluation, and management of carotid body tumors: Systematic analysis based on available evidence.

OBJECTIVE: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to December 1, 2022, for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9291 patients and 9862 tumors were identified. The pooled results indicated that the median age of patients with CBT was 45.72 years, and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. Sixteen percent of patients experienced multiple paragangliomas, and 12% of CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared with non-PE, PE reduced the estimated blood loss (standardized mean difference, -0.95; 95% confidence interval [CI], -1.70 to -0.20) and the operation time (standardized mean difference, -0.56; 95% CI, -1.03 to -0.09), but it increased the incidence of stroke (odds ratio, 2.44; 95% CI, 1.04-5.73). Higher Shamblin grade tumors were associated with more operative complications. Patients who were SDH gene mutation-positive were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the estimated blood loss and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. Patients who were SDH gene mutation-positive had the most relevant family histories and symptoms.

The value of color doppler ultrasonography combined with computed tomography angiography and magnetic resonance angiography in the preoperative quantification and classification of carotid body tumors: a retrospective analysis.

BACKGROUND: Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) provide accurate vascular imaging information, but their use may be contraindicated. Color Doppler ultrasonography (CDU) provides simple, safe, noninvasive, and reproducible imaging. We therefore investigated the role of preoperative CDU combined with CTA and MRA in the quantification, typing, and diagnosis of carotid body tumors (CBTs). METHODS: We retrospectively analyzed patients with CBTs categorized into group A (type I [n = 1] and type II [n = 10]) or group B (type III [n = 56]) per the intraoperative Shamblin classification. CDU, CTA, and MRA characteristics of CBTs were observed, surgical results were correlated, and the diagnostic threshold of the CBT classification was calculated. RESULTS: CBTs were usually located at the common carotid artery bifurcation, encircling the carotid artery. An increased angle was found between the internal and external carotid arteries. On CDU, CBTs primarily presented as homogeneous hypoechoic masses with clear boundaries, rich flow signals, and a high-speed, low-resistance artery-like flow spectrum. CTA showed uniform or heterogeneous marked enhancement. MRA showed mixed T1 and slightly longer T2 signals and uniform or uneven obvious enhancement. With increases in the lesion size, amount of blood transfused, and operation time, the intraoperative classification level and possibility of skull-base invasion increased. When the maximum diameter of the lesion, the volume of the tumor, the distance between the upper margin of the tumor to the mastoid and the mandibular angle were 3.10 cm, 10.15 cm3, - 3.26 cm, and 0.57 cm, respectively, the largest Youden index was the best diagnostic boundary value for Shamblin type III tumors. CONCLUSIONS: CDU combined with CTA and MRA can accurately evaluate the size and classification of CBTs.

Novel insights into the classification of Shamblin III carotid body tumors from a neurosurgical perspective.

BACKGROUND AND PURPOSE: The classic Shamblin system fails to provide valuable guidance in many Shamblin's III carotid body tumors (III-CBTs) due to the variable forms of carotid arteries and the complex anatomic relationships in parapharyngeal space. We proposed a modified classification to separately divide III-CBTs into different subgroups on the basis of arterial relevant features and anatomical relevant features. MATERIALS AND METHODS: From 2020 to 2023, a total of 129 III-CBTs at a single institution were retrospectively analyzed. All cases were independently classified as arterial-relevant and anatomical-relevant subgroups. The pre-, peri- and postoperative data were summarized and compared accordingly. RESULTS: Among the 129 cases, 69 cases were identified as "Classical type", 23 cases as "Medial type", 27 cases as "Lateral type" and 10 cases as "Enveloped type" according to arterial morphologies. Besides, 76 cases were identified as "Common type", 15 cases as "Pharynx- invasion type", 18 cases as "Skull base-invasion type" and 20 cases as "Mixed type" according to anatomical relationships. "Enveloped type" of tumors in arterial-relevant classification and "Mixed type" of tumors in anatomical-relevant classification are the most challenging cases for surgeons with the lowest resection rate, highest incidence of carotid arteries injury and postoperative stroke. CONCLUSION: The modified classifications provide comprehensive understanding of different III-CBTs which are applicable for individualized treatment in clinical practice.

Ruptured carotid artery pseudoaneurysm following excision of a carotid body tumor: a rare complication managed successfully with surgery and literature review.

A 47-year-old male presented with a right-sided Shamblin type 2 carotid body tumor measuring 5*5 cm. After preoperative embolization, a sub adventitial resection of the tumor was done. He was discharged after postoperative day 5 and presented again to emergency 10 days later with a bleeding pseudoaneurysm at the surgical site causing dysphagia and dyspnea. He was taken for emergency exploration of the surgical wound and, intraoperatively, it was observed that the proximal ends of the internal carotid artery and external carotid artery close to the bifurcation were forming a pseudoaneurysm, 1 cm distal to the common carotid artery. The external carotid artery was ligated and a common carotid to internal carotid artery bypass was done with a reversed saphenous vein graft. He recovered well in the postoperative period and was discharged on day 7. Pseudoaneurysm formation following carotid body tumor resection is extremely rare and has only been reported thrice in the literature.

Um homem de 47 anos apresentou tumor carotídeo Shamblin tipo 2 no lado direito, medindo 5 x 5 cm. Após embolização pré-operatória, foi realizada ressecção subadventicial do tumor. O paciente teve alta no quinto dia pós-operatório e voltou à emergência 10 dias depois, com pseudoaneurisma hemorrágico no sítio operatório causando disfagia e dispneia. Foi levado para exploração emergencial da ferida cirúrgica, e, no intraoperatório, 1 cm distalmente à artéria carótida comum, as extremidades proximais da artéria carótida interna e da artéria carótida externa próximas à bifurcação formavam um pseudoaneurisma. A artéria carótida externa foi ligada, e foi realizada uma ponte de safena de carótida comum para a artéria carótida interna com a veia safena invertida. O paciente se recuperou bem no pós-operatório e recebeu alta no sétimo dia. A formação de pseudoaneurisma após ressecção de tumor do corpo carotídeo é extremamente rara, tendo sido relatada apenas três vezes na literatura.

An analysis from the CAPACITY database of outcomes of preoperative embolization before carotid body tumor surgery compared with resection alone.

OBJECTIVE: There is no definitive consensus on the impact of preoperative embolization on carotid body tumor (CBT) treatment. The objective of this study was to compare surgical outcomes of patients who underwent preoperative embolization before CBT resection vs patients who underwent resection alone. METHODS: The CAPACITY registry included 1432 patients with CBT from 11 medical centers in four different countries. The group of patients undergoing CBT resection with preoperative embolization was matched in a 1:6 ratio from a pool of patients from the CAPACITY database, using a generated propensity score with patients who did not underwent preoperative embolization. RESULTS: A total of 553 patients were included for analysis. Mean patient age was 56.23 ± 12.22 years. Patients were mostly female (n = 469; 84.8%). Bilateral CBT was registered in 60 patients (10.8%). Seventy-nine patients (14.3%) underwent preoperative embolization. Embolized patients had larger CBT sizes than non-embolized patients (33.8 mm vs 18.4 mm; P = .0001). Operative blood loss was lower in the embolized group compared with the non-embolized group (200 mL vs 250 mL; P = .031). Hematomas were more frequent in the non-embolized group (0% vs 2.7%; P = .044). Operative time, rates of stroke, cranial nerve injuries, and death were not statistically significant between groups. CONCLUSIONS: Embolization before CBT resection was associated with significantly lower blood loss and lower neck hematomas than patients who underwent resection alone. Operative time, stroke, cranial nerve injuries, and death were similar between groups.

Effect of distance to the base of skull and tumor size characteristics on cranial nerve injuries in carotid body tumor resections.

OBJECTIVE: In the present study, we aimed to confirm the findings reported by Kim et al. They stated that the tumor's distance to the base of the skull was predictive of injury to the cranial nerves and their branches during carotid body tumor resection in an Austrian cohort. METHODS: In the present retrospective observational trial, we included all consecutive patients who had been discharged from our tertiary care teaching hospital with the diagnosis of a carotid body tumor (CBT) between January 2004 and December 2019. Tumor-specific parameters were measured from the preoperative contrast-enhanced computed tomography or magnetic resonance imaging studies. Patient-specific data were obtained from the patients' medical records. The effect of these parameters on the occurrence of cranial nerve injuries was calculated using univariate logistic regression analysis. Parameters significant on univariate analysis were included in a multivariate model. RESULTS: A total of 48 CBTs had been resected in 43 patients (29 women [67.4%] and 14 men [32.6%]), with a mean age of 55.6 years (95% confidence interval, 51.8-58.5). The mean distance to the base of the skull was 43.2 mm (95% confidence interval, 39.9-46.5). A total of 18 injuries to the cranial nerves and their branches in 10 CBTs were detected. The tumor-specific parameters that were significant on univariate analysis were the distance to the base of the skull (P = .009), craniocaudal tumor diameter (P = .027), and tumor volume (P = .036). Stepwise multivariate logistic regression analysis revealed that the distance to the base of the skull was the only parameter that remained statistically significant. CONCLUSIONS: We found that the distance to the base of the skull is a highly predictive parameter for injuries to the cranial nerves and their branches during CBT resection and should be included in the surgical risk assessment and patient information.

Preoperative embolization is necessary for large-volume carotid body tumor (≥ 6670 mm3) resection.

BACKGROUND: To investigate the impact of preoperative embolization (p-TAE) on CBT surgical resection and explore the optimal tumor volume for p-TAE of CBT resection. METHODS: This retrospective study reviewed 139 surgically excised CBTs. According to Shamblin classification, tumor volumes, and whether to carry out the p-TAE, the patients were classified into different groups. The demographic, clinical features, and the intraoperative and post-operative information about the patients were retrieved and analyzed from the patient records. RESULTS: A total of 139 CBTs was excised in 130 patients. According to the results of subgroup analysis, there were no significant differences in surgical time, blood loss, adverse events (AEs), and the revascularization when compared with non-embolization group (NEG) for type I, II, III, respectively (all p > 0.05) except for the surgical time in type I (p < 0.05). Then the X-tile program was employed and determine the cutoff point (tumor volume = 6670 mm3) for tumor volumes and blood loss. The average tumor volume was (29,782.37 vs. 31,345.10 mm3, p = 0.65) for embolization group (EG) and NEG. The mean surgical time (208.86 vs. 264.67 min, p > 0.05) and intraoperative blood loss (252.78 vs. 430.00 mL, p < 0.05) were less, and the incidence of revascularization required (35.56 vs. 52.38%, p > 0.05) and total complications (27.78 vs. 57.14%, p < 0.05) were lower in EG when compared with NEG (tumor volume ≥ 6670 mm3). However, the results were not statistically significant when the tumor size was less than 6670 mm3. No surgery-related mortality was observed during the follow-up. CONCLUSIONS: Preoperative selective embolization of CBT is an effective and safe adjunct for surgical resection, especially for Shamblin class II and III tumors (≥ 6670 mm3).

BILATERAL CAROTID BODY PARAGANGLIOMAS - LITERATURE REVIEW AND COMMENTS IN A PATIENT WITH NO SIGNS OF MEN SYNDROME.

Paragangliomas are rare neuroendocrine slow-growing tumors, often asymptomatic, that originate from embryonic neural crest cell. In the head and neck area, the most common location is the carotid body, followed, with decreasing frequency, in jugular, tympanic and vagal sites. Bilateral carotid body tumors are extremely rare. Aim: To present the most important features of carotid body paragangliomas, illustrating the clinical characteristics, associated with a thorough analysis of the diagnostic imaging elements, but also the current therapeutic strategies, with respective anatomical, surgical considerations and potential complications that can occur. Surgical resection is the main line of treatment. The complex anatomy of the cervical region and the close relationships of carotid body paragangliomas with carotid vessels and cranial nerves, as well as its intense vascularization makes the surgical intervention a real challenge even for an experienced surgeon. Discussion: Starts from a bilateral carotid paraganglioma in a 35-year-old male, with painless lateral neck swelling, accidentally discovered by his barber about two years ago. Diagnosis was suspected on the basis of history, clinical and radiological findings. "Wait and scan" strategy plus endocrinologic assessment for MEN syndromes were considered the optimal therapeutic approach in this case.

Epidemiology and survival of patients with malignant carotid body tumors in the SEER database.

OBJECTIVE: The objective of this study was to investigate population-based epidemiology, survival outcomes, and prognostic factors of malignant carotid body tumors (CBTs). METHODS: Patients with malignant CBTs who were diagnosed between 1975 and 2018 were screened from nine registries of the Surveillance, Epidemiology, and End Results (SEER) database. Cases that were coded as "carotid body tumor, malignant" or malignant tumors with the primary site recorded as "carotid body" were screened for inclusion in the study. The incidence of malignant CBT was calculated with SEER∗Stat software. Survival outcomes were analyzed using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 72 patients with malignant CBT were screened for inclusion in the study, including 41 females (56.9%) and 31 males (43.1%). Based on the SEER program data, the incidence of malignant CBT was found to fluctuate between 0 to 0.02 cases per 100,000 people per year, with a slow but noticeable uptick after 1990. The most commonly affected populations included women and patients between the ages of 35 and 44, which accounted for 59.9% and 27.8% of patients in the study, respectively. During a median follow-up of 82 months, four patients were lost to follow-up, and 28 deaths were identified. Of those, 20 were considered disease-specific deaths. Further analysis found that the 5-year and 10-year overall survival rates were 78.9% and 67.8%, respectively, whereas the 5-year and 10-year disease-specific survival rates were 84.5% and 75.2%, respectively. The Kaplan-Meier method and log-rank tests indicated that age <50 years, sex, race, tumor number, and surgical treatment were unrelated to both overall survival and disease-specific survival. CONCLUSIONS: A retrospective review of the SEER database found that the incidence of malignant CBT was extremely rare and prone to fluctuation, but that it slowly trended upward over time. Malignant CBT was found to more likely affect females, and it could be diagnosed at any age. The overall prognosis for malignant CBT appeared to be good, with acceptable 5-year and 10-year survival rates. Due to a number of factors complicating malignant CBT surgery, surgical treatment should be considered with caution.

Paragangliomas of the head and neck.

Paragangliomas are rare neuroendocrine tumors that can be found from the skull base to the pelvis. Head and neck paragangliomas have been historically treated with surgery. However, surgical resection adds risk of injury to vascular structures and cranial nerves that can lead to morbidity such as hoarseness, dysarthria, dysphagia, or aspiration. Recently, improved understanding of the behavior of these tumors and increasing experience in non-surgical treatments, such as observation and radiation therapy, have changed the paradigms of management of this entity. Multiple series now show a trend toward a more conservative management, with a higher percentage of patients being observed or treated with radiotherapy. Several factors should be taken into consideration when deciding the most appropriate treatment for head and neck paragangliomas, starting by differentiating carotid body tumors from non-carotid body tumors. In general, surgical resection is normally recommended for carotid body tumors as the complications from treatment are usually minimal. In contrast, for non-carotid body tumors, surgery is often associated with significant functional impairment due to cranial nerve paralysis. As such, non-surgical treatment is now usually recommended for this subset of head and neck paragangliomas. In young patients with no comorbidities and a small to medium carotid body tumors, surgery should be considered. Moreover, surgery should be offered for secreting tumors, malignant tumors, tumors with rapid growth or increase in symptomatology, and when radiotherapy cannot be performed. Conversely, conservative management with active surveillance or radiotherapy can be offered in the remaining cases in order to avoid unnecessary morbidity while still providing acceptable tumor control.

Perioperative blood pressure and heart rate alterations after carotid body tumor excision: a retrospective study of 108 cases.

BACKGROUND: Arising from chemoreceptor cells, carotid body tumors (CBTs) are rare neoplasms associated with hemodynamics. Perioperative changes in blood pressure (BP) and heart rate (HR) are not completely understood. METHODS: This retrospective, observational, controlled study included all CBT patients from 2013 to 2018 in Peking Union Medical College Hospital. Perioperative changes in BP/HR within or between unilateral/bilateral/control groups were investigated. Perioperative details across Shamblin types were also assessed. RESULTS: This study included 108 patients (116 excised CBTs). The postoperative systolic BP and HR increased in both unilateral (mean difference of systolic BP = 5.9mmHg, 95% CI 3.1 ~ 8.6; mean difference of HR = 3.7 bpm, 95% CI 2.6 ~ 4.9) and bilateral (mean difference of systolic BP = 10.3mmHg, 95% CI 0.6 ~ 19.9; mean difference of HR = 8.4 bpm, 95% CI 0.5 ~ 16.2) CBT patients compared with the preoperative measures. Compared with control group, the postoperative systolic BP increased (difference in the alteration = 6.3mmHg, 95% CI 3.5 ~ 9.0) in unilateral CBT patients; both systolic BP (difference in the alteration = 9.2mmHg, 95% CI 1.1 ~ 17.3) and HR (difference in the alteration = 5.3 bpm, 95% CI 1.0 ~ 9.6) increased in bilateral CBT patients. More CBT patients required extra antihypertensive therapy after surgery than controls (OR = 2.5, 95% CI 1.14 ~ 5.5). Maximum tumor diameter, intraoperative vascular injury, continuous vasoactive agent requirement, total fluid volume, transfusion, estimated blood loss, operation duration, postoperative pathology, overall complications, and intensive care unit/hospital lengths of stay significantly varied among Shamblin types. CONCLUSION: CBT excision may be associated with subtle perioperative hemodynamic changes. Perioperative management of CBT patients necessitates careful assessment, full preparation and close postoperative monitoring.

Necessity of Intraoperative Level IIA Lymph Node Dissection in Patients with Carotid Body Tumors: A Retrospective Study of 126 Cases.

BACKGROUND: Carotid body tumors (CBTs) are relatively uncommon neoplasms that rarely have malignant potential. However, malignant CBTs (MCBTs) are still associated with a poor prognosis and the treatment is still challenging clinically. Therefore, we evaluated the necessity of intraoperative level IIA lymph node dissection in patients with CBT. METHODS: The clinical characteristics, intraoperative details, and pathological diagnosis of 126 CBT patients who had undergone surgery were retrospectively reviewed. The patients were divided into 2 groups according to whether level IIA lymph node dissection was performed. The prognosis was analyzed using Kaplan-Meier curves and Cox model multivariate survival analysis. RESULTS: Among the 126 patients, 7 patients (10.3%) in the selective lymph node dissection (SLND) group (68 patients) were diagnosed with MCBTs with evidence of lymph node metastasis. Two patients (3.4%) in the lymph node nondissection (LNND) group (58 patients) were diagnosed with MCBTs later after the second operation because they could not be diagnosed as malignant initially because of the lack of lymph node pathology results although the pathology of the primary lesion showed features of malignancy. The SLND group had a significantly higher relapse-free survival rate than the LNND group (94.1% vs. 79.3%, p = 0.021). Patients with a confirmed diagnosis had a better prognosis than those with insufficient evidence of a malignancy due to the lack of lymph node information. Twenty-nine patients in the SLND group and 26 patients in the LNND group had postoperative nerve injuries, with no significant difference between the groups (p = 0.879). CONCLUSION: Intraoperative dissection of level IIA lymph nodes around the tumor in CBT patients can help improve the diagnosis and prognosis of MCBTs without causing additional cranial nerve injury.

[Modern conceptions on neck paragangliomas]. / Paragangliomy shei.

Neck paragangliomas are orphan diseases with incidence 1:30 000-1:100 000. Life expectancy is poor in patients with distant metastasis (5-year overall survival 11.8%), whereas 5-year overall survival in patients with regional metastasis is 76.8-82.4%. Meanwhile, there is still no any reliable tool for prediction of malignant potential of paraganglioma. Above-mentioned data indicate an importance of early diagnosis and timely treatment of neck paragangliomas. Total resection of tumor in ablastic conditions is a gold standard of treatment. However, surgery is associated with a high risk of neurovascular complications and requires multidisciplinary approach. Nevertheless, new knowledge dedicated to different aspects of pathogenesis of neck paraganglioma, diagnosis and treatment arise every year. This review is devoted to modern data on neck paragangliomas.

Surgical outcomes and factors associated with malignancy in carotid body tumors.

OBJECTIVE: To compare the surgical outcomes of benign and malignant carotid body tumor (CBT), and to evaluate the associated factors of malignant CBT. METHODS: Patients who underwent surgical resection of CBT from 2005 to 2018 in a tertiary center were reviewed retrospectively. The common study follow-up end date was December 31, 2019. The tumor size was measured as the maximum transverse diameter on computed tomography scan. Surgical outcomes of benign and malignant CBT were compared. Associated factors of malignancy were analyzed by multivariate logistic analysis. RESULTS: There were 229 patients undergoing CBT resection. Sixteen patients were diagnosed with malignant CBT. The median follow-up time was 66 months (range, 6-142 months). Basic information including age, sex, course of disease, family history, lesion side, tumor size, and Shamblin classification showed no significant differences between the benign and malignant CBT groups. Patients with malignant CBTs showed a higher rate of preoperative symptoms (31.3% vs 12.2%; P < .05). The rates of vascular reconstruction or repair (P < .01) and neurologic complications (P < .05) were significantly higher in the malignant CBT group. In addition, a significantly longer average procedural time was required for malignant CBTs (P < .05). However, the estimated blood loss and length of hospital stay showed no significant difference. Multivariate logistic regression analysis revealed that the malignant odds of CBT with bilateral lesions (P = .0042; odds ratio, 8.30; 95% confidence interval, 1.84-35.88) or CBT with preoperative symptoms (P = .0016; odds ratio, 7.59; 95% confidence interval, 2.13-27.89) were high. CONCLUSIONS: Compared with benign CBT, malignant CBT is prone to invasive clinical behaviors, resulting in an increased possibility of vascular reconstruction or repair during the surgery as well as postoperative neurologic complications. In addition, the malignant odds of CBT with bilateral lesions or CBT with preoperative symptoms are high.

Multispecialty surgical management of carotid body tumors in the modern era.

OBJECTIVE: The objective of this study was to assess the perioperative and long-term outcomes of carotid body tumor (CBT) resection with a multispecialty (head and neck surgery/vascular surgery) approach. METHODS: Our institutional data registry was queried for Current Procedural Terminology codes (60600, 60605) pertaining to CBT excision. These patient records and operative reports were individually reviewed to determine laterality, preoperative tumor embolization, operative time, estimated blood loss, need for intraoperative transfusion, intraoperative electroencephalogram changes, intraoperative division of the external carotid artery, carotid artery repair, resection of the carotid bifurcation, tumor volume, final pathology, cranial nerve injury, stroke, death, and clinical or radiographic evidence of recurrence. RESULTS: From 1996 to 2018, 74 CBT resections were identified in 68 patients (41 [60%] females; mean age, 50.83 years). The mean tumor volume was 9.92 ± 14.26 cm3 (range, 0.0250-71.0627 cm3). Embolization was performed by a neurointerventional specialist in 27 CBT resections (36%) based on size (embolization 14.27 ± 16.84 cm3 vs 7.17 ± 11.86 cm3; P = .063) and superior extension. This practice resulted in one asymptomatic vertebral dissection, which postponed the surgery. There was a trend toward greater blood loss in the embolization group (embolization 437 ± 545 mL vs 262 ± 222 mL; P = .17); however, no transfusions were required in any patient. The mean operative time was also significantly longer in the embolization group (198.33 ± 61.13 minutes vs 161.5 ± 55.56 minutes; P = .03). Three resections had reversible intraoperative electroencephalogram changes, one of which occurred during carotid clamping. These changes resolved with shunting. Eight external carotid resections (11%) and 6 carotid reconstructions (8.1%; two primary, two patch, and two primary anastomosis) were required. Malignancy was identified in four tumors (5.4%), accounting for four of the six carotid reconstructions. There were no postoperative cranial nerve injuries, no strokes, no reexplorations, and no deaths. One patient developed transient dysphagia from pharyngeal tumor infiltration. Long-term follow-up (mean, 43 ± 54 months), available in 61 of the 68 patients (89.7%), revealed three (4.4%) recurrences. CONCLUSIONS: This large, single-institution series demonstrates that a multispecialty team combining two surgical skill sets for the treatment of this rare, challenging condition yields unparalleled low complication rates with short operative times. This approach, including long-term surveillance for recurrent disease, should be considered to optimize outcomes of CBT resection.

Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis.

Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56 years (44-69 years). With a median clinical and radiological follow-up of 44 months (9-161 months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p = 0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r = - 0.4, p = 0.001), right-sided tumor (r = - 0.3, p = 0.03), primary SRS (r = - 0.5, p ≤ 0.001), and initial clinical presentation of hearing loss (r = - 0.4, p = 0.001). To achieve a LC ≥ 90%, a median marginal dose (Gy) of 15 (range, 12-30 Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

[Risk Factors for Patients Using Intraoperative Vasopressor Infusions During Carotid Body Tumor Excision].

Objective To investigate the risk factors for patients using intraoperative vasopressor infusions during carotid body tumor(CBT)excision.Patients' mean arterial pressure(MAP)and heart rate(HR)fluctuations as well as their requirements for vasoactive agents during surgery were assessed. Methods The patients receiving CBT excision in Peking Union Medical College Hospital from May 1,2013 to July 31,2017 were included for a retrospective cohort study.The potential factors of intraoperative requirement for vasopressor infusions were investigated using univariate analysis and Logistic multivariate analysis.Furthermore,the relationships of Shamblin types of CBT with intraoperative MAP/HR fluctuations and requirements for vasoactive agents were analyzed. Results A total of 108 patients with 116 CBTs were included.Univariate analysis revealed that maximum tumor diameter >4 cm,intraoperative internal carotid artery injury,internal carotid artery reconstruction,malignant pathology,advanced Shamblin types(type Ⅱ and Ⅲ),estimated blood loss ≥400 ml,and operation duration >4 hours were associated with intraoperative requirements for vasopressor infusions.Logistic analysis showed that Shamblin type Ⅲ(OR=2.286,95% CI=1.324-14.926,P=0.016)and operation duration >4 hours(OR=3.874,95% CI=1.020-14.623,P=0.046)were risk factors for intraoperative requirements for vasopressor infusions during CBT surgery.In addition,Shamblin type Ⅲ was associated with intraoperative abnormal HR elevation and requirements for vasopressors.Conclusions Shamblin type Ⅲ and operation duration>4 hours are risk factors for intraoperative requirements of patients for using vasopressor infusions during CBT surgery.Shamblin type Ⅲ is associated with intraoperative abnormal HR elevation and requirements for vasopressors.

Tumor-specific prognosis of mutation-positive patients with head and neck paragangliomas.

BACKGROUND: Genetic testing to identify succinate dehydrogenase (SDH) mutations in patients with head and neck paraganglioma (HNP) has been in clinical practice for more than a decade. However, the recurrence and metachronous tumor occurrence risks in surgically treated mutation-positive patients are not well studied. METHODS: Clinical and procedural details of consecutive patients who underwent excision for HNP from January 1996 to October 2016 were retrospectively reviewed. End points included recurrence, metachronous tumor detection, and mortality. Germline DNA was tested to identify mutations in SDHx genes. Patients were divided into three groups on the basis of genetic testing: group I, positive; group II, negative; and group III, unknown or offered but not tested. RESULTS: HNP was diagnosed in 268 patients, 214 (147 female; mean age, 47 years) included in this study. Directed genetic testing was performed in 68; mutations were detected in SDH in 47 (69%), a majority SDHD. In group I, 47 patients had 64 procedures for 81 tumors (52 carotid body tumors [CBTs]); 17 (36%) were bilateral, 7 (15%) multiple, 3 (6%) functional, and 7 (15%) malignant. Residual tumor in 10 was significant in 2, managed by radiation therapy and reoperation. Local recurrence was detected in 12 patients (25%) at a median of 8 years; 11 metachronous mediastinal and retroperitoneal paragangliomas were detected in 8 (17%) at a median of 13 years. Systemic metastases occurred in five (10%). Six patients (13%) had more than one recurrence. In group II, 21 patients had 22 procedures for 23 tumors, 17 CBTs. Two (9%) were bilateral and two (9%) malignant. Excision was complete in all with no recurrence or systemic metastasis at last follow-up. For group III, 146 patients underwent 153 procedures for 156 tumors, 95 CBTs; 7 (5%) were bilateral, 2 (1%) multiple, 8 (5%) functional, and 1 (0.6%) malignant. Local recurrence was detected in nine (6%) at a median of 9 years and metachronous HNP in three (2%) at a median of 5 years. Systemic metastases occurred in two (1%). Mortality was 4% in group I and 3% in group III, none procedure or tumor related. Group I (mutation positive) had 10-year overall, recurrence-free, and metachronous tumor-free survival rates of 93%, 69.4%, and 73%, respectively, lower than the other groups (P < .001). CONCLUSIONS: Bilateral, functional, malignant, recurrent, and metachronous tumors are more common in SDH mutation-positive patients with HNP. Overall survival in patients with HNP is high. Metachronous tumors or local recurrences occur late, and long-term follow-up is necessary.

Management and outcomes of vascular reconstruction in carotid body tumor resection: retrospective analysis of 60 cases.

PURPOSE: Carotid body tumors (CBTs) are rare tumors of the head and neck area. We evaluated outcomes after carotid body tumor resection (CBR) requiring vascular reconstruction. METHODS: We retrospectively reviewed the patients, who underwent CBR in our clinic. Medical records were retrospectively reviewed for clinical data, operative details, Shamblin's classification, complications. Comparisons were performed between those undergoing CBR alone and CBR requiring vascular reconstruction (CBR-VASC). RESULTS: Of the 60 patients, who underwent CBR, 29 (48.3%) underwent vascular reconstruction after the tumor resection. In patients; who underwent carotid endarterectomy and reconstruction of a kinked carotid artery, the blood flow measurements obtained before and after the vascular reconstruction were significantly different. The blood flow measurement parameters obtained before and after the vascular reconstruction were not significantly different in patients undergoing primary repair surgery, patch graft angioplasty, and the use of reversed saphenous vein graft procedures. The overall complication rate was 25% (n = 60) for at least one perioperative problem (CBR 6.4% vs. CBR-VASC 44.8%, p > 0.05). While most patients with Shamblin's class I and II tumors underwent CBR, CBR-VASC was performed more frequently in patients with Shamblin's class III tumors (p = 0.016). The tumor size ( p = 0.016), the volume of intraoperative blood loss (p = 0.002), and the length of hospital stay (p = 0.006) were significantly different between the two groups. The length of the operation time (p = 0.154) and the volume of the postoperative blood drainage (p = 0.122) were not different between the two groups. CONCLUSION: The decision for surgical reconstruction should be made by evaluating the carotid artery blood flow before and after CBR. The type of the reconstruction method does not cause differences in the duration of the surgery and does not elevate the complication rates.