Cascade of Complications Following Carotid Body Tumor Excision.
Ontology highlight
ABSTRACT:
SUBMITTER: Garg PK
PROVIDER: S-EPMC8561026 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Paragangliomas are commonly associated with germline and somatic mutations involving at least one of more than thirty causative genes. However, the specific functionality of a number of these genes involved in the formation of paragangliomas has not yet been fully investigated. METHODS:Exome library preparation was carried out using Nextera® Rapid Capture Exome Kit (Illumina, USA). Sequencing was performed on NextSeq 500 System (Illumina). RESULTS:Exome analysis of 52 CBTs revealed potential driver mutations (PDMs) in 21 genes: ARNT, BAP1, BRAF, BRCA1, BRCA2, CDKN2A, CSDE1, FGFR3, IDH1, KIF1B, KMT2D, MEN1, RET, SDHA, SDHB, SDHC, SDHD, SETD2, TP53BP1, TP53BP2, and TP53I13. In many samples, more than one PDM was identified. There are also 41% of samples in which we did not identify any PDM; in these cases, the formation of CBT was probably caused by the cumulative effect of several not highly pathogenic mutations. Estimation of average mutation load demonstrated 6-8 mutations per megabase (Mb). Genes with the highest mutation rate were identified. CONCLUSIONS:Exome analysis of 52 CBTs for the first time revealed the average mutation load for these tumors and also identified potential driver mutations as well as their frequencies and co-occurrence with the other PDMs.
| S-EPMC5836820 | biostudies-literature
Project description:BackgroundCarotid body tumor (CBT) is a rare neoplasm arising from paraganglion located near the bifurcation of the carotid artery. There is great intra-tumor heterogeneity, and CBT development could be associated with both germline and somatic allelic variants. Studies on the molecular genetics of CBT are limited, and the molecular mechanisms of its pathogenesis are not fully understood. This work is focused on the estimation of mutational load (ML) in CBT.MethodsUsing the NextSeq 500 platform, we performed exome sequencing of tumors with matched lymph node tissues and peripheral blood obtained from six patients with CBT. To obtain reliable results in tumors with low ML, we developed and successfully applied a complex approach for the analysis of sequencing data. ML was evaluated as the number of somatic variants per megabase (Mb) of the target regions covered by the Illumina TruSeq Exome Library Prep Kit.ResultsThe ML in CBT varied in the range of 0.09-0.28/Mb. Additionally, we identified several pathogenic/likely pathogenic somatic and germline allelic variants across six patients studied (including TP53 variants).ConclusionsUsing the developed approach, we estimated the ML in CBT, which is much lower than in common malignant tumors. Identified variants in known paraganglioma/pheochromocytoma-causative genes and novel genes could be associated with the pathogenesis of CBT. The obtained results expand our knowledge of the mutation process in CBT as well as the biology of tumor development.
| S-EPMC6416835 | biostudies-literature
Project description:BackgroundCarotid body tumors (CBTs) are rare entities for which surgical resection remains the gold standard. Given their hypervascularity, preoperative embolization is often used; however, controversy exists over whether a benefit is associated. Proponents of embolization argue that it minimizes blood loss and complications. Critics argue that cost and stroke outweigh benefits. This study aimed to investigate the impact of embolization on outcomes following CBT resection.MethodsPatients undergoing CBT resection were identified using the Healthcare Cost and Utilization Project State Inpatient Database for 5 states between 2006 and 2013. Patients were divided into 2 groups: carotid body tumor resection alone (CBTR) and carotid body tumor resection with preoperative arterial embolization (CBETR). Descriptive statistics were calculated using arithmetic means with standard deviations for continuous variables and proportions for categorical variables. Patients were propensity score matched on the basis of sex, age, race, insurance, and comorbidity prior to analysis. Risk-adjusted odds of mortality, stroke, nerve injury, blood loss, and length of stay (LOS) were calculated using mixed-effects regression models with fixed effects for age, race, sex, and comorbidities.ResultsA total of 547 patients were identified. Of these, 472 patients underwent CBTR and 75 underwent CBETR. Mean age was 54.7 ± 16 years. Mean number of days between embolization and resection was 0.65 ± 0.72 days (range 0-3). When compared with CBTR, there were no significant differences in mortality for CBETR (1.35% vs. 0%, P = 0.316), cranial nerve injury (2.7% vs. 0%, P = 0.48), and blood loss (2.7% vs. 6.8%, P = 0.245). Following risk adjustment, CBETR increased the odds of prolonged LOS (odds ratio 5.3, 95% confidence interval 2.1-13.3).ConclusionsCBT resection is a relatively rare procedure. The utility of preoperative tumor embolization has been questioned. This study demonstrates no benefit of preoperative tumor embolization.
| S-EPMC5726906 | biostudies-literature
Project description:IntroductionCholedochal cyst (CC) is a morphological malformation characterized by dilatations of the biliary tree that might present later with clinical symptoms, including jaundice, abdominal pain or pancreatitis.Presentation of caseHere, we reported a 10-month-old female infant with CC presenting with jaundice and a right upper quadrant mass and who was malnourished following a surgical excision of retroperitoneal teratoma one month ago. Laboratory findings were total bilirubin of 14.17 mg/dL, direct bilirubin of 12.24 mg/dL, gamma glutamyl transferase of 1157 U/L, and alkaline phosphatase 187 U/L. Abdominal computed tomography scan showed a CC that caused dilatation of the proximal common bile duct (CBD), common hepatic duct, and intrahepatic bile duct. We decided to perform an explorative laparotomy and found a CC with diameter of 5 cm. Then, we conducted a Roux-en-Y hepaticojejunostomy. Due to hepaticojejunostomy anastomosis leakage, relaparotomies were done. The patient was uneventfully discharged 17 days after the third surgery.DiscussionOur findings are unique because the patient had a normal biliary tree previously and underwent intraabdominal tumor surgery. Notably, besides being an acquired CC, our case might be due to inadvertent bile duct ligation during the first operation or bile duct obstruction as a complication of the first operation.ConclusionsCC should be considered as a potential complication of intraabdominal tumor excision, especially if its location is near the CBD. Roux-en-Y hepaticojejunostomy is still the best choice for CC management.
| S-EPMC7452007 | biostudies-literature
Project description:Numerous case studies have reported spontaneous regression of metastases following tumor excision, but underlying mechanisms are elusive. Here we present a model of metastases regression and latency elicited by the removal of a primary tumor, and identify underlying mechanisms. Human breast cancer cells, expressing highly sensitive luciferase, were implanted into the mammary fat-pad of mice, and the progression of early stage micrometastases, was monitored. Upon establishment of micrometastases, the primary tumor was excised, inducing a robust regression of metastatic signal, resulting in latent foci. In vivo supplementation of tumor secretome immediately upon tumor excision diminished this regression, implicating primary tumor secreted factors in promotion of metastatic growth. In vitro, cancer cell conditioned medium reduced apoptosis and enhanced adhesion of non-confluent cancer cells, and induced angiogenesis in endothelial cells. Cytokine array and proteomic analysis of cancer cells secretome identified 359 extracellular secreted factors, with significant enrichment of angiogenic factors, growth factors activity, focal adhesion, apoptosis, and metalloprotease processes. In vivo blockade of four key potential mediators of these processes, IL-8, PDGFaa, Serpin E1 (PAI-1), and MIF, arrested development of micrometastases. Moreover, high protein levels of these four factors were correlated with poor patient outcome. These results demonstrate regression and latency of metastases following tumor excision and a crucial role for primary tumor secretome in promoting early metastatic stages, suggesting novel mechanisms to control minimal residual disease.
2020-10-07 | PXD008384 | Pride
Project description:Objective ?Treatment for head and neck paragangliomas (HNGPL) can be more harmful than the disease. After diagnosis, an initial period of surveillance is often indicated, and surgery or radiotherapy is reserved for progressive disease. With the aim to optimize this "wait and scan" strategy, we studied growth and possible predictors. Design ?A retrospective cohort study was conducted. Setting ?This study was conducted at a tertiary referral center for patients with HNGPL. Methods ?Tumor volume was estimated for 184 SDHD -related carotid and vagal body paragangliomas using sequential magnetic resonance imaging. Cox regression was used to study predictors of tumor growth. Results ?The estimated fraction of growing tumors ranged from 0.42 after 1?year of follow-up to 0.85 after 11 years. A median growth rate of 10.4 and 12.0% per year was observed for carotid and vagal body tumors, respectively. Tumor location, initial volume, and age ( p ?<?0.05) were included in our prediction model. The probability of growth decreased with increasing age and volume, indicating a decelerating growth pattern. Conclusions ?We created a prediction model (available online), enabling a more individualized "wait and scan" strategy. The favorable natural course of carotid and vagal body paragangliomas was confirmed; although with long follow-up growth will be observed in most cases.
| S-EPMC5680030 | biostudies-literature
Project description:BackgroundNumerous case studies have reported spontaneous regression of recognized metastases following primary tumor excision, but underlying mechanisms are elusive. Here, we present a model of regression and latency of metastases following primary tumor excision and identify potential underlying mechanisms.ResultsUsing MDA-MB-231HM human breast cancer cells that express highly sensitive luciferase, we monitored early development stages of spontaneous metastases in BALB/c nu/nu mice. Removal of the primary tumor caused marked regression of micro-metastases, but not of larger metastases, and in vivo supplementation of tumor secretome diminished this regression, suggesting that primary tumor-secreted factors promote early metastatic growth. Correspondingly, MDA-MB-231HM-conditioned medium increased in vitro tumor proliferation and adhesion and reduced apoptosis. To identify specific mediating factors, cytokine array and proteomic analysis of MDA-MB-231HM secretome were conducted. The results identified significant enrichment of angiogenesis, growth factor binding and activity, focal adhesion, and metalloprotease and apoptosis regulation processes. Neutralization of MDA-MB-231HM-secreted key mediators of these processes, IL-8, PDGF-AA, Serpin E1 (PAI-1), and MIF, each antagonized secretome-induced proliferation. Moreover, their in vivo simultaneous blockade in the presence of the primary tumor arrested the development of micro-metastases. Interestingly, in the METABRIC cohort of breast cancer patients, elevated expression of Serpin E1, IL-8, or the four factors combined predicted poor survival.ConclusionsThese results demonstrate regression and latency of micro-metastases following primary tumor excision and a crucial role for primary tumor secretome in promoting early metastatic growth in MDA-MB-231HM xenografts. If generalized, such findings can suggest novel approaches to control micro-metastases and minimal residual disease.
| S-EPMC7646068 | biostudies-literature
Project description: Not available
| S-EPMC3114940 | biostudies-literature
Project description:BackgroundThere is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications.MethodsThis was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4-month interval (October-December 2014) were eligible for inclusion. The primary outcome was the 30-day major complication rate (Clavien-Dindo grade III-V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital-level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.).ResultsOf 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30-day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147).ConclusionOverweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight.
| S-EPMC4973675 | biostudies-literature
Project description:Removal of carotid body (CB) improves animal models of hypertension (HTN) and heart failure, via withdrawal of chemoreflex-induced sympathetic activation. Effect of CB tumor (CBT) resection on blood pressure (BP) in subjects with HTN is unknown. A retrospective analysis of 20 subjects with HTN (BP?140/90 mmHg or anti-hypertensives use) out of 134 with CBT resection. Short-term (30 days from surgery) and long-term (slope of regressions on time over the entire follow-up) changes in BP and heart rate were adjusted for covariates (interval between readings, total follow-up, number of readings and changes in therapy). Age and duration of HTN were 56±4 and 9±5 years. Adjusted short-term decreases in systolic (SBP: -9.9±3.1, p<0.001) and pulse pressures (PP: -7.9±2.7, p<0.002) were significant and correlated with their respective long-term changes (SBP: r=0.47, p=0.047; PP: r=0.54, p=0.019). There was a strong relationship between adjusted short-term changes in SBP and PP (r=0.64, p<0.004). Six (50% of responders or 33% of the total) had short-term falls of SBP ?10 mmHg and of PP ? 5 mmHg. First study to show that unilateral CBT resection is associated with sustained reduction of BP in hypertensive patients. Targeted CB chemoreflex removal could play a role in the therapy of human HTN.
| S-EPMC4785596 | biostudies-literature