Impact of Center Volume on Cardiopulmonary and Mortality Outcomes after Immune-Checkpoint Inhibitors for Cancer: A Systematic Review and Meta-Analysis.

Immune-checkpoint inhibitors (ICIs) were proven effective in inducing tumor regression. However, its toxicity tends to be fatal. We sought to investigate the hospital volume/outcomes relationship. Databases were searched for studies reporting immune-checkpoint inhibitors adverse events (AEs) in patients with solid-organ malignancies. The outcomes were A) the pooled events rate (PER) of grade 5, grade 3-4, cardiac-related, and pulmonary-related AEs, and B) the assessment of the volume/outcomes relationship. One hundred and forty-seven studies met our inclusion criteria. The PER of grade 5, grade 3-4, and any-grade AEs was 2.75% (95%CI: 2.18-3.47), 26.69% (95%CI: 21.60-32.48), and 77.80% (95%CI: 70.91-83.44), respectively. The PER of pulmonary-related AEs was 4.56% (95%CI: 3.76-5.53). A higher number of annual cases per center was significantly associated with reduced grade 5 (p = 0.019), grade 3-4 (p = 0.004), and cardiac-related AEs (p = 0.035) in the meta-regression. In the current era of cancer immunotherapy, knowledge regarding the early diagnosis and management of immunotherapy-related AEs is essential. Our meta-analysis demonstrates the importance of center volume in improving outcomes and reducing the incidence of severe AEs.

Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

Succinate dehydrogenase mutations in head and neck paragangliomas: A systematic review and meta-analysis of individual patients' data.

BACKGROUND: Head and neck paragangliomas (HNPs) have been associated with gene mutations in the succinate dehydrogenase (SDH) complex, but the clinical significance remains unclear. We sought to explore the demographics, clinical characteristics, treatment methods, and outcomes of SDH-mutated HNPs. METHODS: Databases were systematically searched. Pooled event ratio and relative 95% confidence intervals were calculated for dichotomous outcomes. Meta-regression was performed. Cochran's Q test and I2 test assessed heterogeneity. Funnel plot and Egger's regression test assessed publication bias. RESULTS: Forty-two studies with 8849 patients were included. Meta-regression revealed a significant correlation between multifocality and SDHD mutations (0.03 ± 0.006, p < 0.0001) and between distant metastases and SDHB mutations (0.06 ± 0.023, p = 0.008). There was no correlation between sex, age, tumor size, or familial occurrences and SDH-related mutations. CONCLUSION: Multifocality of HNPs correlates with the SDHD mutational subtype, and metastases correlate with the SDHB subtype. Knowledge of HNP phenotypes associated with SDH-related mutations has the potential to influence the management approach to such HNPs.

Primary Cardiac Schwannoma: A Meta-Analysis of Individual Case Reports.

Primary cardiac schwannoma (PCS) is a neurogenic tumor that arises from Schwann cells. Malignant schwannoma (MSh) is an aggressive cancer comprising 2% of all sarcomas. Information on the proper management of these tumors is limited. Four databases were searched for case reports/series of PCS. The primary outcome was overall survival (OS). Secondary outcomes included therapeutic strategies and the corresponding outcomes. Among 439 potentially eligible studies, 53 met the inclusion criteria. The patients included had 43.72 ± 17.76 years and 28.3% were males. Over 50% of patients had MSh, with 9.4% also demonstrating metastases. Schwannoma commonly occurs in the atria (66.0%). Left-sided PCS were more common than right-sided ones. Surgery was performed in almost 90% of the cases; chemotherapy and radiotherapy were used in 16.9% and 15.1% of cases, respectively. Compared to benign cases, MSh occurs at a younger age and is commonly located on the left side. OS of the entire cohort at 1 and 3 years were 60.7%, and 54.0%, respectively. Females and males OS were similar up to 2 years follow-up. Surgery was associated with higher OS (p < 0.01). Surgery is the primary treatment option for both benign and malignant cases and was the only factor associated with a relative improvement in survival.

Volume outcome relationship in post-esophagectomy leak: A systematic review and meta-analysis.

BACKGROUND: Anastomotic leak after esophagectomy carries important short and long-term sequelae. We conducted a systematic review and meta-analysis to determine its association with surgical volume. MATERIALS AND METHODS: A systematic literature review was performed to identify all studies reporting on anastomotic leak after esophagectomy. Studies with <100 cases were excluded. The primary outcome was post-esophagectomy anastomotic leak, while secondary outcomes were operative mortality overall and after anastomotic leak. Pooled event rates (PER) were calculated and association with annual esophagectomy volume by center was investigated. RESULTS: Of the 3,932 retrieved articles, 472 were included (n=177,566 patients). The PER of anastomotic leak was 8.91% [95%CI=8.32; 9.53%]. The PER of early mortality overall and after anastomotic leak was 2.49% [95%CI=2.27; 2.74] and 11.39% [95%CI=9.66; 13.39], respectively. Centers with <37 annual esophagectomies had a higher leak rate compared to those with ≥37 annual esophagectomies (9.58% vs. 8.34%; P=0.040). On meta-regression, surgical volume was inversely associated with the PER of esophageal leak and of early mortality. CONCLUSION: The frequency of anastomotic leaks after esophagectomy, perioperative and leak associated mortality are inversely associated with esophagectomy volume.

Lung Cancer as a Leading Cause among Paraneoplastic Non-Bacterial Thrombotic Endocarditis: A Meta-Analysis of Individual Patients' Data.

Hypercoagulability is strongly associated with cancer and may result in non-bacterial thrombotic endocarditis (NBTE). The aim of our meta-analysis was to explore the demographics and characteristics of this condition in cancer. Databases were systematically searched. The outcomes were to identify the annual trend in premortem diagnosis among the entire cohort and different subgroups and to identify differences in characteristics and survival in the considered population. A total of 121 studies with 144 patients were included. The proportion of marantic endocarditis associated with lung cancer was 0.29 (95% CI, 0.21-0.37; p < 0.001), that associated with pancreatic cancer was 0.19 (95% CI, 0.13-0.27; p < 0.001), that associated with advanced cancer stage (metastasis) was 0.69 (95% CI, 0.61-0.76; p < 0.001), and that associated with adenocarcinoma was 0.65 (95% CI, 0.56-0.72; p < 0.001). Median and 6-month overall survival (OS) were 1.3 months and 32.3%, respectively, with 6-month OS of 20.8% vs. 37.0% in lung vs. other cancers, respectively (p = 0.06) and 42.9% vs. 31.1% among those who underwent intervention vs. those who did not (p = 0.07). Cases discovered in recent years had better survival (HR = 0.98 (95% CI, 0.96-0.99; p = 0.003). While cancer-associated NBTE is a rare entity, lung cancers were the most common tumor site and are frequently associated with more advanced and metastatic cancer stages. The prognosis is dismal, especially among lung cancers.

Geographic variation in malignant cardiac tumors and their outcomes: SEER database analysis.

Introduction: Primary malignant cardiac tumors (PMCTs) are rare. Geographical distribution has been demonstrated to affect cancer outcomes, making the reduction of geographical inequalities a major priority for cancer control agencies. Geographic survival disparities have not been reported previously for PMCT and the aim of this study is to compare the prevalence and the long-term survival rate with respect to the geographic location of PMCTs using the Surveillance, Epidemiology, and End Results (SEER) research plus data 17 registries between 2000 and 2019. Methods: The SEER database was queried to identify geographic variation among PMCTs. We classified the included states into 4 geographical regions (Midwest, Northeast, South and West regions) based on the U.S. Census Bureau-designated regions and divisions. Different demographic and clinical variables were analyzed and compared between the four groups. Kaplan Meier curves and Cox regression were used for survival assessment. Results: A total of 563 patients were included in our analysis. The median age was 53 years (inter-quartile range (IQR): 38 - 68 years) and included 26, 90, 101, and 346 patients from the Midwest, Northeast, South, and West regions respectively. Sarcoma represented 65.6% of the cases, followed by hematological tumors (26.2%), while mesothelioma accounted for 2.1%. Treatment analysis showed no significant differences between different regions. Median overall survival was 11, 21, 13, and 11 months for Midwest, Northeast, South and West regions respectively and 5-year overall survival was 22.2%, 25.4%, 14.9%, and 17.6% respectively. On multivariate Cox regression, significant independent predictors of late overall mortality among the entire cohort included age (Hazard Ratio [HR] 1.028), year of diagnosis (HR 0.967), sarcoma (HR 3.36), surgery (HR 0.63) and chemotherapy (HR 0.56). Conclusion: Primary malignant cardiac tumors are rare and associated with poor prognosis. Sarcoma is the most common pathological type. Younger age, recent era diagnosis, surgical resection, and chemotherapy were the independent predictors of better survival. While univariate analysis revealed that patients in the South areas had a worse survival trend compared to other areas, geographic disparity in survival was nullified in multivariate analysis.

Novel Mediastinoscope-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Minimally invasive surgery is an expanding field of surgery that has replaced many open surgical techniques. Surgery remains a cornerstone in the treatment of esophageal cancer, yet it is still associated with significant morbidity and technical difficulties. Mediastinoscope-assisted esophagectomy is a promising technique that aims to decrease the surgical burden and enhance recovery. METHODS: PubMed, MEDLINE, and EMBASE databases were searched for publications on mediastinoscope-assisted esophagectomies for esophageal cancer. The primary endpoint was a postoperative anastomotic leak, while secondary endpoints were assessment of harvested lymph nodes (LNs), blood loss, chyle leak, hospital length of stay (LOS), operative (OR) time, pneumonia, wound infection, mortality, and microscopic positive margin (R1). The pooled event rate (PER) and pooled mean were calculated for binary and continuous outcomes respectively. RESULTS: Twenty-six out of the 2274 searched studies were included. The pooled event rate (PER) for anastomotic leak was 0.145 (0.1144; 0.1828). The PERs for chyle leak, recurrent laryngeal nerve injury/hoarseness, postoperative pneumonia, wound infection, early mortality, postoperative morbidity, and microscopically positive (R1) resection margins were 0.027, 0.185, 0.09, 0.083, 0.020, 0.378, and 0.037 respectively. The pooled means for blood loss, hospital stay, operative time, number of total harvested LNs, and number of harvested thoracic LNs were 159.209, 15.187, 311.116, 23.379, and 15.458 respectively. CONCLUSIONS: Mediastinoscopic esophagectomy is a promising minimally invasive technique, avoiding thoracotomy, patient repositioning, and lung manipulation; thus allowing for shorter surgery, decreased blood loss, and decreased postoperative morbidity. It can also be reliable in terms of oncological safety and LN dissection.

Comparison of meta-analytical estimates of outcomes after Alfieri or neochordal repair in isolated anterior mitral prolapse.

OBJECTIVES: Repair of the isolated degenerative anterior mitral leaflet has been considered more challenging and associated with compromised durability compared with isolated posterior leaflet in major series. Implantation of neochordae or Alfieri edge-to-edge is the most employed repair technique for isolated anterior repair currently, but little data exist comparing their relative durability. We sought to investigate this issue with this meta-analysis. METHODS: A literature search was performed (Ovid MEDLINE, Ovid Embase and The Cochrane Library). The primary outcome was the incidence rate (IR) of reoperation, the secondary outcomes were recurrent moderately severe/severe mitral regurgitation (MR), in-hospital/30-day reoperation and mortality and follow-up mortality. A random-effect model was used. Leave-one-out, subgroup analysis (Alfieri versus neochordae) and meta-regression were done. RESULTS: Seventeen studies (including 1358 patients) were included. At a weighted mean follow-up of 5.56 ± 3.31 years, the IR for reoperation was 14.45 event per 1000 person-year and significantly lower in Alfieri than neochordae repair (9.40 vs 18.61, P = 0.04) on subgroup analysis. The IR of follow-up moderately severe/severe MR was 19.89 event per 1000 person-year and significantly lower in Alfieri than neochordae repair (10.68 and 28.63, P = 0.01). In a sensitivity analysis comparing homogenous studies, a significant difference in the recurrence of regurgitation in favour of the Alfieri approach remained. There were no differences in operative outcomes or survival. There were significant associations between increased incidence of late reoperation and New York Heart Association class III/IV and associated coronary artery bypass graft procedure for whole cohort. CONCLUSIONS: Alfieri repair may be associated with a lower incidence of recurrent MR compared with neochordae-based repair in the setting of isolated degenerative anterior mitral pathology. This is the first such meta-analysis and further inquiry into this area is needed.

Mortality after sternal reconstruction with pectoralis major flap vs omental flap for postsurgical mediastinitis: A systematic review and meta-analysis.

BACKGROUND: Deep sternal wound infections are rare but severe complications after median sternotomy and can be managed with sternal reconstruction. The use of pectoralis major flap (PMF) has traditionally been the first-line approach for flap reconstruction but the advantage in patients' survival when compared to the omental flap (OF) transposition is still not clear. We performed a study-level meta-analysis evaluating the association of the type of flap on postoperative outcomes. METHODS: A systematic search of the literature was performed to identify all studies comparing the postoperative outcomes of PMF versus OF for sternal reconstruction. The primary outcome was postoperative mortality. Secondary outcomes were the occurrence of sepsis, pneumonia, operative time, and length of stay. Binary outcomes were pooled using an inverse variance method and reported as odds ratio (OR) with corresponding 95% confidence interval (CI). Continuous outcomes were pooled using an inverse variance method and reported as standardized mean difference (SMD) with corresponding 95% CI. RESULTS: Four studies with a total of 528 patients were included in the analysis. Overall, 443 patients had PMF reconstruction, and 85 patients had OF reconstruction. Baseline characteristics were similar in both groups. There were no statistically significant differences between PMF patients and OF patients in mortality (OR 0.6 [0.16; 2.17]; p = .09), sepsis (OR 1.1 [0.49; 2.47]; p = .43), pneumonia (OR 0.72 [0.18; 2.8]; p = .11), length of stay (SMD -0.59 [-2.03; 0.85]; p < .01), and operative time (SMD 0.08 [-1.21; 1.57]; p < .01). CONCLUSION: Our analysis found no association between the type of flap and postoperative mortality, the incidence of pneumonia, sepsis, operation time, and length of stay.

Outcomes of Octogenarians with Primary Malignant Cardiac Tumors: National Cancer Database Analysis.

Data concerning age-related populations affected with primary malignant cardiac tumors (PMCTs) are still scarce. The aim of the current study was to analyze mortality differences amongst different age groups of patients with PMCTs, as reported by the National Cancer Database (NCDB). The NCDB was retrospectively reviewed for PMCTs from 2004 to 2017. The primary outcome was late mortality differences amongst different age categories (octogenarian, septuagenarian, younger age), while secondary outcomes included differences in treatment patterns and perioperative (30-day) mortality. A total of 736 patients were included, including 72 (9.8%) septuagenarians and 44 (5.98%) octogenarians. Angiosarcoma was the most prevalent PMCT. Surgery was performed in 432 (58.7%) patients (60.3%, 55.6%, and 40.9% in younger age, septuagenarian, and octogenarian, respectively, p = 0.04), with a corresponding 30-day mortality of 9.0% (7.0, 15.0, and 38.9% respectively, p < 0.001) and a median overall survival of 15.7 months (18.1, 8.7, and 4.5 months respectively). Using multivariable Cox regression, independent predictors of late mortality included octogenarian, governmental insurance, CDCC grade II/III, earlier year of diagnosis, angiosarcoma, stage III/IV, and absence of surgery/chemotherapy. With increasing age, patients presented a more significant comorbidity burden compared to younger ones and were treated more conservatively. Early and late survival outcomes progressively declined with advanced age.

Learning curve and volume outcome relationship of endoscopic trans-oral versus trans-axillary thyroidectomy; A systematic review and meta-analysis.

BACKGROUND: In the modern era, minimally invasive surgery is rapidly evolving and even replacing conventional open techniques in many surgical fields. Thyroidectomy was not an exception, with the introduction of multiple endoscopic thyroidectomy techniques. Trans-oral endoscopic trans-vestibular thyroidectomy (TOT) is a novel technique with promising outcomes. We conducted this meta-analysis to compare surgical outcomes and learning curves for TOT and other endoscopic thyroidectomy techniques. METHODS: A systematic review in PubMed, MEDLINE, and EMBASE databases was conducted searching for publications on TOT versus trans-axillary thyroidectomy (TAT). The primary endpoint was operative (OR) time. Secondary endpoints were number of harvested lymph nodes (LNs), estimated blood loss (EBL), recurrent laryngeal nerve (RLN) injury, hoarseness, seroma, infection, chyle leak, hypocalcemia, hospital length of stay (LOS), and Cost. We also investigated the learning curve for each technique. Leave-out-out analysis, meta-regression, and subgroup analysis were used. Random effect inverse variance method was utilized. RESULTS: Among 3820 retrieved studies, 15 studies (10 unmatched and 5 matched), with 2173 (TOT: 1024(47.12%) and TAT:1149(52.87%)) patients, met the inclusion criteria. The operative time and harvested L. Ns number were higher in TOT versus TAT (standard mean difference (SMD) = 0.72 [95%CI 0.07; 1.37], P = 0.029 and SMD = 0.32 [95%CI 0.02; 0.62], P = 0.036 respectively) while less EBL in TOT versus TAT (SMD = -0.26 [-0.43; -0.09], P = 0.0018). All other outcomes showed no significant difference between both groups. Weighted mean values for TOT and TAT were 158.03 vs 144.97 min for OR time, 6.33 vs 5.16 for harvested LNs, and $5,919.05 vs $6,253.79 for the cost. Statistical significance in learning curve development was noticed ranging between 6 and 15 annual cases. CONCLUSION: Trans-oral thyroidectomy is a safe and reliable technique with outcomes comparable to other endoscopic techniques. It provides better access to the central compartment with a more feasible LN dissection. Improvement in surgical outcomes is expected with growing learning curve and technique mastery.