Closing the RCT Gap-A Large Meta-Analysis on the Role of Surgery in Stage I-III Small Cell Lung Cancer Patients.

INTRODUCTION: Despite clear guideline recommendations, surgery is not consistently carried out as part of multimodal therapy in stage I small cell lung cancer (SCLC) patients. The role of surgery in stages II and III is even more controversial. In the absence of current randomized control trials (RCT), we performed a meta-analysis comparing surgery versus non-surgical treatment in stage I to III SCLC patients. METHODS: A systematic review of the literature was conducted on 1 July 2023, focusing on studies pertaining to the impact of surgery on small cell lung cancer (SCLC). These studies were evaluated using the ROBINS-I tool. Statistical analyses, including I² tests, Q-statistics, DerSimonian-Laird tests, and Egger regression, were performed to assess the data. In addition, 5-year survival rates were analyzed. The meta-analysis was conducted according to PRISMA standards. RESULTS: Among the 6826 records identified, 10 original studies encompassing a collective cohort of 95,323 patients were incorporated into this meta-analysis. Heterogeneity was observed across the included studies, with no discernible indication of publication bias. Analysis of patient characteristics revealed no significant differences between the two groups (p-value > 0.05). The 5-year survival rates in a combined analysis of patients in stages I-III were 39.6 ± 15.3% for the 'surgery group' and 16.7 ± 12.7% for the 'non-surgery group' (p-value < 0.0001). SCLC patients in stages II and III treated outside the guideline with surgery had a significantly better 5-year survival compared to non-surgery controls (36.3 ± 20.2% vs. 20.2 ± 17.0%; p-value = 0.043). CONCLUSIONS: In the absence of current RCTs, this meta-analysis provides robust suggestions that surgery might significantly improve survival in all SCLC stages. Non-surgical therapy could lead to a shortening of life. The feasibility of surgery in non-metastatic SCLC should always be evaluated as part of a multimodal treatment.

Histology of the Primary Tumor Correlates with False Positivity of Integrated 18F-FDG-PET/CT Lymph Node Staging in Resectable Lung Cancer Patients.

This study aimed to evaluate the diagnostic accuracy and false positivity rate of lymph node (LN) staging assessed by integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in patients with operable lung cancer to the tumor histology. In total, 129 consecutive patients with non-small-cell lung cancer (NSCLC) undergoing anatomical lung resections were included. Preoperative LN staging was evaluated in the relationship to the histology of the resected specimens (group 1: lung adenocarcinoma/LUAD; group 2: squamous cell carcinoma/SQCA). Statistical analysis was performed by the Mann-Whitney U-test, the chi2 test, and binary logistic regression analysis. To establish an easy-to-use algorithm for the identification of LN false positivity, a decision tree including clinically meaningful parameters was generated. In total, 77 (59.7%) and 52 (40.3%) patients were included in the LUAD and SQCA groups, respectively. SQCA histology, non-G1 tumors, and tumor SUVmax > 12.65 were identified as independent predictors of LN false positivity in the preoperative staging. The corresponding ORs and their 95% CIs were 3.35 [1.10-10.22], p = 0.0339; 4.60 [1.06-19.94], p = 0.0412; and 2.76 [1.01-7.55], and p = 0.0483. The preoperative identification of false-positive LNs is an important aspect of the treatment regimen for patients with operable lung cancer; thus, these preliminary findings should be further evaluated in larger patient cohorts.

Are Routine Chest X-rays Necessary following Thoracic Surgery? A Systematic Literature Review and Meta-Analysis.

(1) Background: The number of chest X-rays that are performed in the perioperative window of thoracic surgery varies. Many clinics X-ray patients daily, while others only perform X-rays if there are clinical concerns. The purpose of this study was to assess the evidence of perioperative X-rays following thoracic surgery and estimate the clinical value with regard to changes in patient care. (2) Methods: A systematic literature research was conducted up until November 2021. Studies reporting X-ray outcomes in adult patients undergoing general thoracic surgery were included. (3) Results: In total, 11 studies (3841 patients/4784 X-rays) were included. The X-ray resulted in changes in patient care in 488 cases (10.74%). In patients undergoing mediastinoscopic lymphadenectomy or thoracoscopic sympathectomy, postoperative X-ray never led to changes in patient care. (4) Conclusions: There are no data to recommend an X-ray before surgery or to recommend daily X-rays. X-rays immediately after surgery seem to rarely have any consequences. It is probably reasonable to keep requesting X-rays after drain removal since they serve multiple purposes and alter patient care in 7.30% of the cases.

Hyperthermic intrathoracic chemotherapy for the treatment of malignant pleural effusion caused by breast and ovarian cancer: A systematic literature review and pooled analysis.

OBJECTIVES: Breast and ovarian cancer account for over 30% of malignant pleural effusions (MPEs). Treatment of the metastatic disease requires control of the MPE. Even though primarily symptomatic, the treatment of the MPE can potentially affect the oncological course of the disease. The aim of this review is to analyze the effectiveness of intrathoracic chemotherapy in the treatment of MPE caused by breast and ovarian cancer. METHODS: A systematic literature research was conducted up until May 2021. Studies published in English on patients undergoing either surgical or interventional intrapleural chemotherapy were included. RESULTS: Thirteen studies with a total of 497 patients were included. Analysis was performed on 169 patients with MPE due to breast cancer and eight patients with MPE secondary to ovarian cancer. The pooled success rates of intrathoracic chemotherapy for controlling the MPE were 59.1% and 87.5%, respectively. A survival analysis was not possible with the available data. The overall toxicity of the treatment was low. CONCLUSIONS: Intrathoracic chemotherapy achieves symptomatic control of the MPE in 59.1% of patients with metastatic breast cancer and 87.5% of patients with metastatic ovarian cancer. This is inferior to other forms of surgical pleurodesis. Data from small case series and studies on intraperitoneal chemotherapy show promising results. However, formal oncological studies on the use of intrathoracic chemotherapy for metastatic breast or ovarian cancer are lacking. Further prospective pilot studies are needed to assess the therapeutic oncological effects of this treatment.

Computer tomography guided thoracoscopic resection of small pulmonary nodules in the hybrid theatre.

PURPOSE: Thoracic surgeons are currently asked to resect smaller and deeper lesions which are difficult to detect thoracoscopically. The growing number of those lesions arises both from lung cancer screening programs and from follow-up of extrathoracic malignancies. This study analyzed the routine use of a CT-aided thoracoscopic approach to small pulmonary nodules in the hybrid theatre and the resulting changes in the treatment pathway. METHODS: 50 patients were retrospectively included. The clinical indication for histological diagnosis was suspected metastasis in 46 patients. Technically, the radiological distance between the periphery of the lesion and the visceral pleura had to exceed the maximum diameter of the lesion for the patient to be included. A spiral wire was placed using intraoperative CT-based laser navigation to guide the thoracoscopic resection. RESULTS: The mean diameter of the lesions was 8.4 mm (SD 4.27 mm). 29.4 minutes (SD 28.5) were required on average for the wire placement and 42.3 minutes (SD 20.1) for the resection of the lesion. Histopathology confirmed the expected diagnosis in 30 of 52 lesions. In the remaining 22 lesions, 9 cases of primary lung cancer were detected while 12 patients showed a benign disease. CONCLUSION: Computer tomography assisted thoracoscopic surgery (CATS) enabled successful resection in all cases with minimal morbidity. The histological diagnosis led to a treatment change in 42% of the patients. The hybrid-CATS technique provides good access to deeply located small pulmonary nodules and could be particularly valuable in the emerging setting of lung cancer screening.

Risk factors for surgical complications after anatomic lung resections in the era of VATS and ERAS.

BACKGROUND: The aim of this study was to identify risk factors for surgical complications after anatomic lung resections in the era of video-assisted thoracic surgery (VATS) and enhanced recovery after surgery (ERAS). METHODS: A retrospective analysis of all consecutive adult patients who underwent elective anatomic lung resections between January and December 2020 at our institution was performed. RESULTS: Eighty patients (40 VATS, 40 thoracotomy) were included. The 30-day mortality rate was 1.3%. The overall rate of major postoperative complications was 18.8%. Most major complications occurred in patients who underwent open surgery (complication rate 32.5%, share of total complications 86.7%). Major morbidity after VATS resection was rare (complication rate 2.5%, share of total complications 13.3%). In univariable analysis, thoracotomy (p = 0.003), impaired preoperative lung function (p = 0.003), complex surgery (p = 0.004) and sleeve resection (p = 0.037) were associated with adverse outcomes. In multivariable analysis, thoracotomy (p = 0.044) and impaired preoperative lung function (p = 0.028) were the only independent risk factors for major postoperative morbidity. CONCLUSION: Thoracotomy was associated with a 10-fold increased risk for postoperative complications compared with minimally invasive surgery and was an independent risk factor for surgical complications. In the era of VATS and ERAS, the fact that thoracotomy is performed may be a reliable parameter to identify patients at risk for postoperative complications.

Autologous blood pleurodesis for the treatment of postoperative air leaks. A systematic review and meta-analysis.

BACKGROUND: Postoperative air leaks are a common complication after lung surgery. They are associated with prolonged hospital stay, increased postoperative pain and treatment costs. The treatment of prolonged air leaks remains controversial. Several treatments have been proposed including different types of sealants, chemical pleurodesis, or early surgical intervention. The aim of this review was to analyze the impact of autologous blood pleurodesis in a systematic way. METHODS: A systematic review of the literature was conducted until July 2020. Studies with more than five adult patients undergoing lung resections were included. Studies in patients receiving blood pleurodesis for pneumothorax were excluded. The search strategy included proper combinations of the MeSH terms "air leak", "blood transfusion" and "lung surgery". RESULTS: Ten studies with a total of 198 patients were included in the analysis. The pooled success rate for sealing the air leak within 48 h of the blood pleurodesis was 83.7% (95% CI: 75.7; 90.3). The pooled incidence of the post-interventional empyema was 1.5%, with a pooled incidence of post-interventional fever of 8.6%. CONCLUSIONS: Current evidence supports the idea that autologous blood pleurodesis leads to a faster healing of postoperative air leaks than conservative treatment. The complication rate is very low. Formal recommendations on how to perform the procedure are not possible with the current evidence. A randomized controlled trial in the modern era is necessary to confirm the benefits.

Transplanted fibroblasts proliferate in host bronchial tissue and enhance bronchial anastomotic healing in a rodent model.

INTRODUCTION: Healing of airway anastomoses after preoperative irradiation can be a significant clinical problem. The augmentation of bronchial anastomoses with a fibroblast-seeded human acellular dermis (hAD) was shown to be beneficial, although the underlying mechanism remained unclear. Therefore, in this study we investigated the fate of the fibroblasts transplanted to the scaffold covering the anastomosis. MATERIAL AND METHODS: 32 Fisher rats underwent surgical anastomosis of the left main bronchus. In a 2 × 2 factorial design, they were randomized to receive preoperative irradiation of 20 Gy and augmentation of the anastomosis with a fibroblast-seeded transplant. Fibroblasts from subcutaneous fat of Fischer-344 rat were transduced retrovirally with tdTomato for cell tracking. After 7 and 14 days, animals were sacrificed and cell concentration of transplanted and nontransplanted fibroblasts in the hAD as well as in the bronchial tissue was measured using RT-PCR. RESULTS: Migration of transplanted fibroblasts from dermis to bronchus were demonstrated in both groups, irradiated and nonirradiated. In the irradiated groups, there was a cell count of 7 × 104 ± 1 × 104 tomato+-fibroblasts in the bronchial tissue at day 7, rising to 1 × 105 ± 1 × 104 on day 14 (p <0.0001). Tomato+-cell concentration in hAD increased from 6 × 103 ± 1 × 103 at day 7 to 6 × 104 ± 1 × 104 at day 14 (p <0.0001). In the nonirradiated groups, tomato+-cell concentration in bronchus was 4 × 103 ± 1 × 103 on day 7 and 4 × 103 ± 1 × 103 at day 14. In the hAD tomato+ cell concentration rising from 1 × 104 ± 1 × 103 at day 7 to 2 × 104 ± 3 × 103 cells at day 14 (p = 0.0028). CONCLUSIONS: Transplanted fibroblasts in the irradiated groups proliferate and migrate into the irradiated host bronchial tissue, but not in the nonirradiated groups.

Computed Tomography-Assisted Thoracoscopic Surgery: A Novel, Innovative Approach in Patients With Deep Intrapulmonary Lesions of Unknown Malignant Status.

OBJECTIVES: Minimally invasive resection of small, deep intrapulmonary lesions can be challenging due to the difficulty of localizing them during video-assisted thoracoscopic surgery (VATS). We report our preliminary results evaluating the feasibility of an image-guided, minimally invasive, 1-stop-shop approach for the resection of small, deep intrapulmonary lesions in a hybrid operating room (OR). MATERIALS AND METHODS: Fifteen patients (5 men, 10 women; mean age, 63 years) with a total of 16 solitary, deep intrapulmonary nodules of unknown malignant status were identified for intraoperative wire marking. Patients were placed on the operating table for resection by VATS. A marking wire was placed within the lesion under 3D laser and fluoroscopic guidance using a cone beam computed tomography system. Then, wedge resection by VATS was performed in the same setting without repositioning the patient. RESULTS: Complete resection with adequate safety margins was confirmed for all lesions. Marking wire placement facilitated resection in 15 of 16 lesions. Eleven lesions proved to be malignant, either primary or secondary; 5 were benign. Mean lesion size was 7.7 mm; mean distance to the pleural surface was 15.1 mm (mean lesion depth-diameter ratio, 2.2). Mean procedural time for marking wire placement was 35 minutes; mean VATS duration was 36 minutes. CONCLUSIONS: Computed tomography-assisted thoracoscopic surgery is a new, safe, and effective procedure for minimally invasive resection of small, deeply localized intrapulmonary lesions. The benefits of computed tomography-assisted thoracoscopic surgery are 1. One-stop-shop procedure, 2. Lower risk for the patient (no patient relocation, no marking wire loss), and 3. No need to coordinate scheduling between the CT room and OR.

Effect of dynamic seeding methods on the distribution of fibroblasts within human acellular dermis.

The purpose of this investigation was to compare different dynamic cell seeding methods regarding their seeding efficiency, homogeneity, infiltration depth and proliferation within a human acellular dermis. In addition, the growth behaviour was observed during a 12-day static in vitro culture. The dynamic methods included orbital-shaker seeding and the use of a plate centrifuge with different rotational speeds, combinations of low-pressure for matrix degassing and centrifugal seeding. Scaffolds were incubated for up to 12 days statically. Cell distribution and infiltration depth were analysed histologically at days 0, 4, 8 and 12. Seeding efficiency and cell proliferation were quantified with the MTT-assay at the same time points. Centrifugal seeding with 300g for 5 × 1 min combined with matrix degassing significantly increased the seeding efficiency and homogeneity compared to the other methods. However, following static culture, no cells were detectable after 4 days in the inner matrix zones. Furthermore, none of the degassing+centrifugation groups reached a significantly higher proliferation at day 8 compared to the reference. The use of a single dynamic method resulted in an inefficient cell seeding. We archived the highest seeding efficiency, homogeneity and infiltration depth using a combination of degassing+centrifugation at 300g for 5 × 1 min.

Effect of static seeding methods on the distribution of fibroblasts within human acellular dermis.

INTRODUCTION: When developing tissue engineered solutions for existing clinical problems, cell seeding strategies should be optimized for desired cell distribution within matrices. The purpose of this investigation was to compare the effects of different static cell seeding methods and subsequent static cell culture for up to 12 days with regard to seeding efficiency and resulting cellular distribution in acellular dermis. MATERIALS AND METHODS: The seeding methods tested were surface seeding of both unmodified and mechanically incised dermis, syringe injection of cell suspension, application of low-pressure and use of an ultrasonic bath to remove trapped air. The effect of "platelet derived growth factor" (PDGF) on surface seeding and low pressure seeding was also investigated. Scaffolds were incubated for up to 12 days and were histologically examined at days 0, 4, 8 and 12 for cell distribution and infiltration depth. The metabolic activity of the cells was quantified with the MTT assay at the same time points. RESULTS: The 50 ml syringe degassing procedure produced the best results in terms of seeding efficiency, cell distribution, penetration depth and metabolic activity within the measured time frame. The injection and ultrasonic bath methods produced the lowest seeding efficiency. The incision method and the 20 ml syringe degassing procedure produced results that were not significantly different to those obtained with a standard static seeding method. CONCLUSION: We postulate that air in the pores of the human acellular dermis (hAD) hinders cell seeding and subsequent infiltration. We achieved the highest seeding efficiency, homogeneity, infiltration depth and cell growth within the 12 day static culturing period by degassing the dermis using low- pressure created by a 50 ml syringe. We conclude that this method to eliminate trapped air provides the most effective method to seed cells and to allow cell proliferation in a natural scaffold.

Mechanical properties of mesh materials used for hernia repair and soft tissue augmentation.

BACKGROUND: Hernia repair is the most common surgical procedure in the world. Augmentation with synthetic meshes has gained importance in recent decades. Most of the published work about hernia meshes focuses on the surgical technique, outcome in terms of mortality and morbidity and the recurrence rate. Appropriate biomechanical and engineering terminology is frequently absent. Meshes are under continuous development but there is little knowledge in the public domain about their mechanical properties. In the presented experimental study we investigated the mechanical properties of several widely available meshes according to German Industrial Standards (DIN ISO). METHODOLOGY/PRINCIPAL FINDINGS: Six different meshes were assessed considering longitudinal and transverse direction in a uni-axial tensile test. Based on the force/displacement curve, the maximum force, breaking strain, and stiffness were computed. According to the maximum force the values were assigned to the groups weak and strong to determine a base for comparison. We discovered differences in the maximum force (11.1±6.4 to 100.9±9.4 N/cm), stiffness (0.3±0.1 to 4.6±0.5 N/mm), and breaking strain (150±6% to 340±20%) considering the direction of tension. CONCLUSIONS/SIGNIFICANCE: The measured stiffness and breaking strength vary widely among available mesh materials for hernia repair, and most of the materials show significant anisotropy in their mechanical behavior. Considering the forces present in the abdominal wall, our results suggest that some meshes should be implanted in an appropriate orientation, and that information regarding the directionality of their mechanical properties should be provided by the manufacturers.