Surgery最新文献

Background: Recent multigenomic analysis of adrenocortical carcinomas (ACCs) identified SLC7A11/xCT as a novel biomarker. The Food and Drug Administration-approved anti-inflammatory drug, sulfasalazine (SAS), induces ferroptosis by blocking SLC7A11 expression. We hypothesize that SAS could be repurposed to target ACC cells.

Methods: Expression of SLC7A11 and its association with ACC survival was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). The validated ACC cell lines NCI-H295R, ACC1, and ACC2 were grown in 2D culture. In vitro studies included the CellTiter-Glo assay to calculate viability, Western blot (WB) analysis for apoptosis and other target protein changes, reverse transcriptase polymerase chain reaction for steroidogenic enzyme changes, C11BODIPY for lipid peroxidation, and mass spectrometry for changes in lipids.

Results: The Cancer Genome Atlas Program database analysis in GEPIA showed that SLC7A11 and linked long noncoding RNA OAP5-AS1 are highly expressed in ACC tumors versus normal adrenals (n = 77 vs 128; P < .05). This was associated with poor overall and disease-free survival with hazard ratios of 4.3 and 5.2 for SLC7A11 and 4.8 and 2.7 for OAP5-AS1, respectively. ACC cell line half-inhibitory maximum concentration values after 72-hour SAS treatment ranged from 412 nM (ACC1) to 799 nM (ACC2), and all showed cleavage of poly (ADP-ribose) polymerase, upregulation of p-Akt and p-ERK, and downregulation of GPX4 and SLC7A11 (P < .05) by WB analysis. Sphere formation, migration, and invasion assay showed inhibition, and lipid peroxidation using C11BODIPY, increase in intracellular iron, induction of oxidative stress, and significant upregulation of oxidized polyunsaturated fatty acid phospholipids (P < .05 each) by mass spectrometry suggests induction of ferroptosis.

Conclusion: SAS downregulates tSLC7A11 in ACCs, targets the Akt/ERK pathway and lipid metabolism, and induces cell death in vitro, warranting additional translational studies to define its therapeutic potential in ACC.

Background: Thyroid cancers with mutations in the phosphatidylinositol-3 kinase/AKT pathway have a poorer prognosis. However, knowledge about the relationship between histology, mutation profile, and outcomes is still developing. This study assessed the prognostic value of genomic profiles for patients with advanced thyroid cancer who experienced progression on conventional treatment.

Methods: Patients recruited to a national clinical oncology program for treatment-refractory locally advanced, recurrent or metastatic cancers were analyzed. Patients' archival tumor samples underwent comprehensive genomic profiling. Specific oncogenic mutations and the presence of cancer related pathways were correlated with overall survival.

Results: From 2018 to 2021, 4,955 patients were recruited, with 44 (0.9%) having a diagnosis of thyroid cancer with 4 medullary and the remaining follicular derived: 17 differentiated, 13 poorly differentiated, and 10 anaplastic thyroid cancers. Of the 40 follicular-derived thyroid cancer samples, 17 (42.5%) carried TP53 mutations, followed by 11 with BRAF V600E (27.5%), 9 with NRAS (22.5%), 9 with mutations in the phosphatidylinositol-3 kinase/AKT pathway (22.5%), and 7 with TERT promoter mutations (17.5%). Both TP53 and phosphatidylinositol-3 kinase/AKT pathway alterations were associated with reduced overall survival (hazard ratio, 5.19; 95% confidence interval, 1.59-16.70, P = .02 and hazard ratio, 10.12; 95% confidence interval, 1.61-63.76, P = .01). Cox regression showed histologic type anaplastic thyroid cancer (hazard ratio, 12.93, P = .004), poorly differentiated thyroid cancer (hazard ratio, 5.19, P = .039), and TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations (hazard ratio, 4.73, P = .017) were independently associated with overall survival.

Conclusion: TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations correlated with overall survival independently of histotype in patients with advanced thyroid cancer. Comprehensive genomic profiling has potential to inform prognosis, as well as identifying treatment targets for patients with advanced thyroid cancer.

Background: Improvements in surgical techniques and perioperative care as well as increased patient life expectancies have led cardiothoracic surgeons to perform more complex operations, including reoperative open-heart surgeries. However, there is debate as to which patients are appropriate operative candidates for reoperative procedures.

Methods: This is a retrospective, single-center study of patients who underwent reoperative open-heart surgery via median sternotomy or thoracotomy over a 10-year period. Patients with previous ventricular assist device or heart transplant were excluded. Patients were stratified by age <65 years compared with age ≥65 years for analysis. Survival was assessed using Kaplan-Meier curves and log-rank tests. Multivariate analysis was performed with Cox proportional hazards regression.

Results: A total of 250 patients underwent reoperative open-heart surgery at our center from 2012 to 2022. In total, 176 patients underwent valve surgery, 53 underwent coronary artery bypass grafting, 31 underwent aortic surgery, and 29 underwent other operations. The overall mortality rate was 13.6% at 30 days and 21.2% at 1-year postoperatively. Patients ≥65 years old had a greater average survival compared with patients <65 years old (5.0 vs 4.1 years, P = .046). However, there were no differences in survival by age when patients were stratified by procedure, either coronary artery bypass grafting (P = .29) or valve surgery (P = .16). On multivariate analysis, reoperative valve surgery, intraoperative use of extracorporeal membrane oxygenation, and a greater number of reoperative surgeries were associated with lower survival.

Conclusion: Patients undergoing reoperative open-heart surgery are clinically complex and had lower survival with each subsequent reoperation.

Background: Patients diagnosed with pathologic T1N0 esophageal squamous cell carcinoma and treated with surgery alone have a good prognosis and are generally followed up without adjuvant therapy. However, recurrence has been observed in this patient group. Therefore, this study aimed to identify recurrence and prognostic factors in patients with pathologic T1N0 esophageal squamous cell carcinoma who were treated with surgery alone.

Methods: Of the 532 patients who underwent esophagectomy with R0 resection at Hiroshima University Hospital between August 2003 and November 2018, 124 who underwent only esophagectomy and had pathological T1N0 esophageal squamous cell carcinoma were included in the study. Recurrence and prognostic factors were analyzed and details of recurrence were evaluated.

Results: The 5-year recurrence-free survival and 5-year overall survival rates were 84.7% and 87.2%, respectively. Recurrence was observed in 12 (9.7%) patients. Univariate and multivariate analyses showed that the histologic type (poorly differentiated compared with others) and lymphatic and/or vascular invasion (positive compared with negative) were statistically significant for recurrence-free survival. Kaplan-Meier curves for recurrence-free survival and overall survival showed that prognosis was significantly stratified according to these factors. All patients with poorly differentiated and positive lymphatic and/or vascular invasion experienced recurrence and recurrence pattern is all distant metastases.

Conclusions: Poorly differentiated and lymphatic and/or vascular invasion are important recurrence and prognostic predictors in pathologic T1N0 esophageal squamous cell carcinoma treated with surgery alone. Patients with these prognostic factors experienced increased recurrence rates, often with distant metastasis. Therefore, adjuvant therapy may be beneficial for such patients and follow-ups should be performed at closer intervals.

Background: Tertiary hyperparathyroidism adversely affects kidney allografts, with calcium phosphate deposition hypothesized to be an underlying cause. We analyzed allograft biopsies to investigate risk factors for calcium phosphate deposition and understand its impact on allograft function.

Methods: We reviewed patients who underwent kidney transplantation from 2017 to 2019. Tertiary hyperparathyroidism was defined as an elevated parathyroid hormone and hypercalcemia beyond 3 months' posttransplant or being prescribed cinacalcet. Allograft failure was defined as needing dialysis posttransplantation or retransplantation beyond 3 months' posttransplant. Three- and 12-month allograft biopsies were reviewed for calcium phosphate deposition. The χ², t-test, and multivariate regression were used for statistical analysis.

Results: Of 159 patients who underwent kidney transplantation, 59 (37.1%) were diagnosed with tertiary hyperparathyroidism. Longer preoperative dialysis vintage (odds ratio, 1.47; confidence interval, 1.22-1.80 P < .001) and preoperative cinacalcet usage (odds ratio, 18.4; confidence interval, 7.24-53.0 P < .001) were associated with tertiary hyperparathyroidism. In total, 36 of 59 (61%) patients with tertiary hyperparathyroidism had calcium phosphate deposition on 3- or 12-month kidney allograft biopsy compared with 23 of 100 (23%) patients without tertiary hyperparathyroidism (P < .001). Tertiary hyperparathyroidism (odds ratio, 6.01; confidence interval, 2.91-13.0 P < .001) was associated with calcium phosphate deposition. Calcium phosphate deposition and tertiary hyperparathyroidism were not associated with worse glomerular filtration rate at 3 years' posttransplantation. Of those with data available at 3 years' posttransplantation, 21 of 49 (42.9%) patients remained on cinacalcet. There were 3 of 159 (2%) patients who had allograft failure, 2 of whom had both tertiary hyperparathyroidism and calcium phosphate deposition.

Conclusion: Preoperative variables associated with tertiary hyperparathyroidism included longer dialysis vintage and cinacalcet use. Tertiary hyperparathyroidism was the main risk factor for calcium phosphate deposition posttransplantation. In our population, calcium phosphate deposition and tertiary hyperparathyroidism were not significantly associated with lower glomerular filtration rate.