Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell Lung Cancer

Purpose: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival.

Methods: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible.

Results: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency.

Conclusion: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.

Models of cardiovascular surgery biobanking to facilitate translational research and precision medicine

Biobanking in health care has evolved over the last few decades from simple biological sample repositories to complex and dynamic units with multi-organizational infrastructure networks and has become an essential tool for modern medical research. Cardiovascular tissue biobanking provides a unique opportunity to utilize cardiac and vascular samples for translational research into heart failure and other related pathologies. Current techniques for diagnosis, classification, and treatment monitoring of cardiac disease relies primarily on interpretation of clinical signs, imaging, and blood biomarkers. Further research at the disease source (i.e. myocardium and blood vessels) has been limited by a relative lack of access to quality human cardiac tissue and the inherent shortcomings of most animal models of heart disease. In this review, we describe a model for cardiovascular tissue biobanking and databasing, and its potential to facilitate basic and translational research. We share techniques to procure endocardial samples from patients with hypertrophic cardiomyopathy, heart failure with reduced ejection fraction, and heart failure with preserved ejection fraction, in addition to aortic disease samples. We discuss some of the issues with respect to data collection, privacy, biobank consent, and the governance of tissue biobanking. The development of tissue biobanks as described here has significant scope to improve and facilitate translational research in multi-omic fields such as genomics, transcriptomics, proteomics, and metabolomics. This research heralds an era of precision medicine, in which patients with cardiovascular pathology can be provided with optimized and personalized medical care for the treatment of their individual phenotype.

Step-by-step harvesting of various grafts for coronary artery bypass surgery

One of the key aspects to obtain good long-term outcomes after coronary artery bypass grafting is graft quality. Meticulous graft harvesting is an important technical aspect in successfully performing high-quality coronary surgery and is associated with improved long-term graft patency. Hence, developing surgical skills in this necessary surgical step is of utmost importance in coronary bypass surgery. The following video tutorial presents a step-by-step audiovisual description of the skeletonized harvesting technique of the left internal mammary artery, open and endoscopic radial artery harvesting, and open saphenous vein graft harvesting.

Post-operative outcomes of inflammatory thoracic aortitis: a study of 41 patients from a cohort of 1119 surgical cases.

Aortitis is found in 2-12% of thoracic aortic aneurysm repair/replacement surgeries. Yet little is known about such patients’ post-operative outcomes or the role of post-operative corticosteroids. The study was undertaken across three tertiary referral hospitals in Sydney, Australia. Prospectively collected data for all thoracic aortic repair/replacement patients between 2004 and 2018 was accessed from a national surgical registry and analysed. Histopathology records identified cases of inflammatory aortitis which were subclassified as clinically isolated aortitis (CIA), giant cell arteritis (GCA), Takayasu (TAK) or other aortitis. Between-group outcomes were compared utilising logistic and median regression analyses. Between 2004 and 2018, a total of 1119 thoracic aortic surgeries were performed of which 41 (3.7%) were inflammatory aortitis cases (66% CIA, 27% GCA, 5% TAK, 2% other). Eight out of 41 (20%) aortitis patients received post-operative corticosteroids. Compared to non-aortitis patients, the aortitis group was predominantly female (53.7% vs. 28.1%, p < 0.01), was older (mean 70 vs. 62 years, p < 0.01) and had higher prevalence of hypertension (82.9% vs. 67.1%, p = 0.03) and pre-operative immunosuppression (9.8% vs. 1.4%, p < 0.01). There was no difference (p > 0.05) between aortitis and non-aortitis groups for 30-day mortality (7.3% vs 6.5%), significant morbidity (14.6% vs. 22.4%), or infection (9.8% vs. 6.4%). Outcomes were similar for the non-corticosteroid-treated aortitis subgroup. Histologic evidence of inflammatory thoracic aortitis following surgery did not affect post-operative mortality or morbidity. Withholding corticosteroids did not adversely affect patient outcomes. These findings will assist rheumatologists and surgeons in the post-operative management of aortitis

Meta-analysis of intentional sublobar resections versus lobectomy for early stage non-small cell lung cancer

Background: Surgical resection is the preferred treatment modality for eligible candidates with non-small cell lung cancer (NSCLC). However, the selection of sublobar resection versus lobectomy for early-stage NSCLC remains controversial. Previous meta-analyses comparing these two procedures presented data without considering the significant differences in the patient selection processes in individual studies. The present study aimed to compare the overall survival (OS) and disease-free survival (DFS) outcomes of patients who underwent sublobar resections who were also eligible for lobectomy procedures with those who underwent lobectomy.

Methods: An electronic search was conducted using five online databases from their dates of inception to December 2013. Studies were selected according to predefined inclusion criteria and meta-analyzed using hazard ratio (HR) calculations.

Results: Twelve studies met the selection criteria, including 1,078 patients who underwent sublobar resections and 1,667 patients who underwent lobectomies. From the available data, there was no significant differences in OS [HR 0.91; 95% confidence interval (CI) 0.64-1.29] or DFS (HR 0.82; 95% CI 0.60-1.12) between the two treatment arms. In addition, no significant OS difference was detected for patients who underwent segmentectomies compared to lobectomies (HR 1.04; 95% CI 0.66-1.63, P=0.86).

Conclusions: Using the available data in the current literature, patients who underwent sublobar resection for small, peripheral NSCLC after intentional selection rather than ineligibility for greater resections achieved similar long-term survival outcomes as those who underwent lobectomies. However, patients included for the present meta-analysis were a highly selected cohort and these results should be interpreted with caution. The importance of the patient selection process in individual studies must be acknowledged to avoid conflicting outcomes in future meta-analyses.

A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin

Background: The objective of the present meta-analysis was to analyze the survival outcomes of patients with colorectal peritoneal carcinomatosis (CRPC), with particular focus on cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC).

Methods: A search was conducted on Medline from 1950 to February 2009 and Pubmed from 1950 to February 2009 for original studies on CRS with PIC. All articles included in this study were assessed with the application of predetermined selection criteria. Results regarding the overall survival in the meta-analysis were expressed as hazard ratios with 95% confidence intervals.

Results: Forty-seven manuscripts were selected in the present systematic review, including 4 comparative studies and 43 observational studies of CRS with PIC. From the meta-analysis, it can be seen that a significant improvement in survival was associated with treatment by CRS and hyperthermic intraperitoneal chemotherapy compared with palliative approach (P < 0.0001). The pooled data did not show a significant improvement in overall survival for patients treated by CRS and early postoperative intraperitoneal chemotherapy versus surgery and systemic chemotherapy (P = 0.35). The overall effect of PIC is significantly better than the control group (P = 0.0002). The current literature suggests that patients with liver metastasis amendable to resection should not be excluded from CRS and PIC. However, there is a need for further evaluation of the prognostic significance of lymph node and liver involvement, ideally in large prospective trials.

Conclusions: The meta-analysis showed that combined therapy involving CRS and PIC had a statistically significant survival benefit over control groups.

Comparison of optimally resected hepatectomy and peritonectomy patients with colorectal cancer metastasis

Background: Hepatectomy is the standard of care for patients with colorectal liver metastases (CRLM) but cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) are still not widely accepted as the definitive treatment for patients with peritoneal carcinomatosis of colorectal origin (CRPC). We analyzed our data to compare survival outcomes for patients in these two groups who achieved optimal resection.

Methods: We examined our prospectively collected database for CRLM and CRPC patients who underwent hepatectomy or peritonectomy from 1995 to 2008.

Results: We identified 46 CRPC patients who achieved CCR-0/CCR-1 and 237 CRLM patients had a margin-negative hepatectomy. CRS patients had 1-, 2-, 3-, 5-year overall survival rates of 83.6%, 65.4%, 51.4%, and 32.1%, respectively. Comparatively, CRLM patients had 1-, 2-, 3-, 5-year overall survival rates of 88.1%, 69.4%, 51.9%, and 33.3%, respectively. Median survival for the two groups were 37.0 months (1-72) for CRPC patients and 37.0 months (0-120) for CRLM patients. There was no statistical significance in overall survival (P = 0.792).

Conclusions: There was no significant difference in survival outcomes for CRLM and CRPC patients who achieved optimal resection. Selected CRPC patients with potentially resectable disease should be considered for CRS and PIC.

Malignant peritoneal mesothelioma

Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.

A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy

Perioperative intraperitoneal chemotherapy in combination with cytoreductive surgery has been shown to be of benefit for treating selected patients with peritoneal surface malignancy. It has become a new standard of care in the management of diffuse malignant peritoneal mesothelioma and peritoneal dissemination of appendiceal malignancy. Numerous recent publications on carcinomatosis from colorectal cancer and gastric cancer identify groups of patients that would benefit from this local-regional approach for prevention and treatment of carcinomatosis. This review focuses on pharmacological information regarding intraperitoneal chemotherapeutic agents commonly used in gastrointestinal oncology.

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