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Cureus Mar 2022This study aimed to compare the outcomes of coblation versus bipolar diathermy in pediatric patients undergoing tonsillectomy. A systematic review and meta-analysis were... (Review)
Review
This study aimed to compare the outcomes of coblation versus bipolar diathermy in pediatric patients undergoing tonsillectomy. A systematic review and meta-analysis were performed per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines. An electronic search of information was conducted to identify all Randomized Controlled Trials (RCTs) comparing the outcomes of coblation versus bipolar in pediatric patients undergoing tonsillectomy. Primary outcome measures were intraoperative bleeding, reactionary hemorrhage, delayed hemorrhage, and post-operative pain. Secondary outcome measures included a return to a normal diet, effects on the tonsillar bed, operation time, and administration of analgesia. Fixed and random-effects models were used for the analysis. Seven studies enrolling 1328 patients were identified. There was a significant difference between coblation and bipolar groups in terms of delayed hemorrhage (Odds Ratio [OR] = 0.27, P = 0.005) and post-operative pain (standardized mean difference [MD] = -2.13, P = 0.0007). Intraoperative bleeding (MD = -43.26, P = 0.11) and reactionary hemorrhage did not show any significant difference. The coblation group improved analgesia administration, diet and tonsillar tissue recovery, and thermal damage for secondary outcomes. No significant difference was reported in terms of operation time. In conclusion, coblation is comparable to a bipolar technique for pediatric patients undergoing tonsillectomy. It improves postoperative pain and delayed hemorrhage and does not worsen intraoperative bleeding and reactionary hemorrhage.
PubMed: 35419233
DOI: 10.7759/cureus.23066 -
International Journal of Surgery... Jul 2023The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased.
OBJECTIVES
The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases.
METHODS
The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software.
RESULTS
Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP.
CONCLUSIONS
CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.
Topics: Humans; Pancreatectomy; Pancreatic Fistula; Retrospective Studies; Pancreas; Pancreatic Neoplasms; Postoperative Complications
PubMed: 37300889
DOI: 10.1097/JS9.0000000000000326 -
The Cochrane Database of Systematic... Feb 2023Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion.
OBJECTIVES
To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss.
SEARCH METHODS
We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes.
AUTHORS' CONCLUSIONS
Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.
Topics: Adult; Humans; Aprotinin; Blood Transfusion; Deamino Arginine Vasopressin; Fibrin Tissue Adhesive; Hemorrhage; Network Meta-Analysis; Tranexamic Acid
PubMed: 36800489
DOI: 10.1002/14651858.CD013649.pub2 -
Arab Journal of Urology 2022To determine the advantages and disadvantages of both methods by comparing classic circumcision methods with circumcision methods assisted by ring instruments. (Review)
Review
AIM
To determine the advantages and disadvantages of both methods by comparing classic circumcision methods with circumcision methods assisted by ring instruments.
MATERIAL-METHODS
Only studies that compared open procedures and ring devices for male circumcision were included. A total of 6226 patients were examined in 14 studies. The methodological quality of RCT was evaluated using Cochrane collaboration's tools. The Review Manager software statistical package was used to analyze the ORs for dichotomous variables and the mean differences for continuous variables. The proportion of heterogeneity across the studies was tested using the I 2 index. Potential publication bias was assessed by identifying the presence of visual asymmetry/symmetry with funnel plot studies.
RESULTS
There were 1812 patients in the open circumcision group and 4414 patients in the ring groups. In total, there was no difference identified between the groups. The open procedure had an advantage compared to the Plastibell subgroup for hemorrhage, while in the other two subgroups, the ring instrument groups had the advantage. Statistically significant in favor of ring devices was found in operating time.There was no difference between the groups for early (postoperative) pain scores. For late-period pain scores, differences with statistical significance were identified in favor of ring devices both in subgroups and in total. For satisfaction, apart from one study in the PrePex group, statistical significance was obtained in favor of ring devices for the other subgroups and in total.
CONCLUSION
The main factors in favor of the use of ring instruments for circumcision are the short total surgical duration, not requiring advanced surgical experience, ease of learning and application, and patient relative satisfaction rates. However, it is a condition to know open circumcision methods and to have experience of this surgery for use in situations with hemorrhage complications, mainly, and without ring instruments of appropriate size.
PubMed: 35935913
DOI: 10.1080/2090598X.2022.2071545 -
The American Journal of Cardiology Sep 2023Alternative vascular accesses to transfemoral access for transcatheter aortic valve replacement (TAVR) can be divided into intrathoracic (IT)-transapical and... (Meta-Analysis)
Meta-Analysis
Alternative vascular accesses to transfemoral access for transcatheter aortic valve replacement (TAVR) can be divided into intrathoracic (IT)-transapical and transaortic- and extrathoracic (ET)-transcarotid, transsubclavian, and transaxillary. This study aimed to compare the outcomes and safety of IT and ET accesses for TAVR as alternatives to transfemoral access. A systematic review with meta-analysis was performed by searching PubMed/MEDLINE and EMBASE databases for all studies comparing IT-TAVR with ET-TAVR published until April 2023. Outcomes included in-hospital or 30-day all-cause mortality (ACM), 1-year ACM, postoperative and 30-day complications. A total of 18 studies with 6,800 IT-TAVR patients and 5,032 ET-TAVR patients were included. IT accesses were associated with a significantly higher risk of in-hospital or 30-day ACM (relative risk 1.99, 95% confidence interval 1.67 to 2.36, p <0.001), and 1-year ACM (relative risk 1.31, 95% confidence interval 1.21 to 1.42, p <0.001). IT-TAVR patients presented more often with postoperative life-threatening bleeding, 30-day new-onset atrial fibrillation or flutter, and 30-day acute kidney injury needing renal replacement therapy. The risks of postoperative permanent pacemaker implantation and significant paravalvular leak were lower with IT-TAVR. ET-TAVR patients were more likely to be directly discharged home. There was no statistically significant difference regarding the 30-day risk of stroke. Compared with ET-TAVR, IT-TAVR was associated with higher risks of in-hospital or 30-day ACM, 1-year ACM and higher risks for some critical postprocedural and 30-day complications. Our results suggest that ET-TAVR could be considered as the first-choice alternative approach when transfemoral access is contraindicated.
Topics: Humans; Transcatheter Aortic Valve Replacement; Acute Kidney Injury; Databases, Factual; Hospitals; Postoperative Hemorrhage
PubMed: 37633682
DOI: 10.1016/j.amjcard.2023.07.091 -
HPB : the Official Journal of the... May 2022Major abdominal surgery and malignancy lead to a hypercoagulable state, with a risk of venous thromboembolism (VTE) of approximately 3% after pancreatic surgery. No... (Review)
Review
BACKGROUND
Major abdominal surgery and malignancy lead to a hypercoagulable state, with a risk of venous thromboembolism (VTE) of approximately 3% after pancreatic surgery. No guidelines exist to assist surgeons in managing VTE prophylaxis or anticoagulation in patients undergoing elective pancreatic surgery for malignancy or premalignant lesions. A systematic review specific to VTE prophylaxis and anticoagulation after resectional pancreatic surgery is herein provided.
METHODS
Six topic areas are reviewed: pre- and perioperative VTE prophylaxis, early postoperative VTE prophylaxis, extended outpatient VTE prophylaxis, management of chronic anticoagulation, anti-coagulation after vascular reconstruction, and treatment of VTE. A Medline and PubMED search was completed with systematic medical literature review for each topic. Level of evidence was graded and strength of recommendation ranked according to the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system for practice guidelines.
RESULTS
Levels of evidence and strength of recommendations are presented.
DISCUSSION
While strong data exist to guide management of chronic anticoagulation and treatment of VTE, data for anticoagulation after reconstruction is inconclusive and support for perioperative chemoprophylaxis with pancreatic surgery is similarly limited. The risk of post-pancreatectomy hemorrhage often exceeds that of thrombosis. The role of universal chemoprophylaxis must therefore be examined critically, particularly in the preoperative setting.
Topics: Anticoagulants; Blood Coagulation; Hemorrhage; Humans; Neoplasms; Risk Factors; Venous Thromboembolism
PubMed: 35063354
DOI: 10.1016/j.hpb.2021.12.010 -
PloS One 2023To comprehensively investigate risk factors for proliferative vitreoretinopathy (PVR) after retinal detachment (RD) surgery. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To comprehensively investigate risk factors for proliferative vitreoretinopathy (PVR) after retinal detachment (RD) surgery.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were systematically searched until May 22, 2023. Risk factors included demographic and disease-related risk factors. Odds ratios (ORs) and weighted mean differences (WMDs) were used as the effect sizes, and shown with 95% confidence intervals (CIs). Sensitivity analysis was conducted. The protocol was registered with PROSPERO (CRD42022378652).
RESULTS
Twenty-two studies of 13,875 subjects were included in this systematic review and meta-analysis. Increased age was associated with a higher risk of postoperative PVR (pooled WMD = 3.98, 95%CI: 0.21, 7.75, P = 0.038). Smokers had a higher risk of postoperative PVR than non-smokers (pooled OR = 5.07, 95%CI: 2.21-11.61, P<0.001). Presence of preoperative PVR was associated with a greater risk of postoperative PVR (pooled OR = 22.28, 95%CI: 2.54, 195.31, P = 0.005). Presence of vitreous hemorrhage was associated with a greater risk of postoperative PVR (pooled OR = 4.12, 95%CI: 1.62, 10.50, P = 0.003). Individuals with aphakia or pseudophakia had an increased risk of postoperative PVR in contrast to those without (pooled OR = 1.41, 95%CI: 1.02, 1.95, P = 0.040). The risk of postoperative PVR was higher among patients with macula off versus those with macula on (pooled OR = 1.85, 95%CI: 1.24, 2.74, P = 0.002). Extent of RD in patients with postoperative PVR was larger than that in patients without (pooled WMD = 0.31, 95%CI: 0.02, 0.59, P = 0.036). Patients with postoperative PVR had longer duration of RD symptoms than those without (pooled WMD = 10.36, 95%CI: 2.29, 18.43, P = 0.012).
CONCLUSION
Age, smoking, preoperative PVR, vitreous hemorrhage, aphakia or pseudophakia, macula off, extent of RD, and duration of RD symptoms were risk factors for postoperative PVR in patients undergoing RD surgery, which may help better identify high-risk patients, and provide timely interventions.
Topics: Humans; Retinal Detachment; Vitreoretinopathy, Proliferative; Vitreous Hemorrhage; Pseudophakia; Risk Factors; Aphakia
PubMed: 37903162
DOI: 10.1371/journal.pone.0292698 -
Cancers Mar 2023To date, gross total resection (GTR) of the contrast-enhancing area of glioblastoma (GB) is the benchmark treatment regarding surgical therapy. However, GB infiltrates... (Review)
Review
A Systematic Review and Meta-Analysis of Supramarginal Resection versus Gross Total Resection in Glioblastoma: Can We Enhance Progression-Free Survival Time and Preserve Postoperative Safety?
To date, gross total resection (GTR) of the contrast-enhancing area of glioblastoma (GB) is the benchmark treatment regarding surgical therapy. However, GB infiltrates beyond those margins, and most tumors recur in close proximity to the initial resection margin. It is unclear whether a supramarginal resection (SMR) enhances progression-free survival (PFS) time without increasing the incidence of postoperative surgical complications. The aim of the present meta-analysis was to investigate SMR with regard to PFS and postoperative surgical complications. We searched for eligible studies comparing SMR techniques with conventional GTR in PubMed, Cochrane Library, Web of Science, and Medline databases. From 3158 initially identified records, 11 articles met the criteria and were included in our meta-analysis. Our results illustrate significantly prolonged PFS time in SMR compared with GTR (HR: 11.16; 95% CI: 3.07-40.52, = 0.0002). The median PFS of the SMR arm was 8.44 months (95% CI: 5.18-11.70, < 0.00001) longer than the GTR arm. The rate of postoperative surgical complications (meningitis, intracranial hemorrhage, and CSF leaks) did not differ between the SMR group and the GTR group. SMR resulted in longer median progression-free survival without a negative postoperative surgical risk profile. Multicentric prospective randomized trials with a standardized definition of SMR and analysis of neurologic functioning and health-related quality of life are justified and needed to improve the level of evidence.
PubMed: 36980659
DOI: 10.3390/cancers15061772 -
Journal of Vascular Surgery May 2022The long-term outcomes after endovascular abdominal aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) have been inferior to those after open surgical repair... (Review)
Review
OBJECTIVE
The long-term outcomes after endovascular abdominal aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) have been inferior to those after open surgical repair with regard to reinterventions and late mortality. AAA sac remodeling after EVAR has been associated with endoleaks, reinterventions, and mortality. Therefore, knowledge of the predictors of AAA sac remodeling could indirectly give insight into the long-term EVAR outcomes. In the present review, we aimed to provide an overview of the evidence for anatomic predictors of positive and negative AAA sac remodeling after EVAR.
METHODS
A systematic literature review and analysis were conducted in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) and Cochrane guidelines. The PubMed and Scopus databases were searched using terms of AAA sac growth, shrinkage, and remodeling. Eligible studies were identified, and only those studies that had included currently used endografts were included.
RESULTS
A total of 19 studies that had reported on a total of 27 anatomic parameters of the aortoiliac anatomy were included. Only 4 parameters had been investigated by more than five studies, 7 parameters were investigated by three to five studies, 7 parameters were investigated by two studies, and 9 parameters were investigated by one study. For the presence of neck thrombus, three of four studies had reported similar results, indicating that the presence of neck thrombus might predict for less AAA sac shrinkage. AAA thrombus, the total AAA volume, the flow-lumen volume, aortic calcification, and the number of hostile neck parameters were only investigated by two to three studies. However, these parameters seemed promising for the prediction of sac remodeling. For hostile neck anatomy, neck length, infrarenal neck angulation, and patency of the inferior mesenteric artery, no significant association with any category of AAA sac remodeling was found.
CONCLUSIONS
The present review demonstrates neck thrombus, AAA thrombus, number of hostile neck parameters, total AAA volume, AAA flow-lumen volume, and aortic calcification as important anatomic features that are likely to play a role in AAA remodeling after endovascular repair and should be further explored using advanced imaging techniques. We also found that strong, consistent evidence regarding the anatomic predictors of AAA sac remodeling after EVAR is lacking. Therefore, further research with large patient groups for a broad range of predictors of AAA sac change after EVAR is needed to complement the current gap in the evidence.
Topics: Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis Implantation; Endoleak; Endovascular Procedures; Humans; Retrospective Studies; Risk Factors; Stents; Treatment Outcome
PubMed: 34952192
DOI: 10.1016/j.jvs.2021.11.071 -
Langenbeck's Archives of Surgery Aug 2023Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity... (Meta-Analysis)
Meta-Analysis Review
The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.
BACKGROUND
Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC).
METHODS
A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS).
RESULTS
Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group.
CONCLUSIONS
This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately.
PROTOCOL REGISTRATION
PROSPERO (CRD42021277495) on the 25th of October 2021.
Topics: Humans; Pancreaticoduodenectomy; Duodenal Neoplasms; Prospective Studies; Pancreas; Postoperative Complications; Laparoscopy; Pancreatic Neoplasms; Retrospective Studies
PubMed: 37581763
DOI: 10.1007/s00423-023-03047-4