Comparing immediate postoperative outcomes of different VATS approaches for anatomical lung resection: a single-centre retrospective study.

BACKGROUND: Video-assisted thoracic surgery (VATS) can be performed through 1 or more intercostal or subxiphoid ports. The aim of this study was to evaluate whether number and location of ports had an impact on early perioperative outcomes and postoperative pain after anatomical lung resection (ALR). METHODS: A search of the departmental electronic database identified all patients who underwent VATS ALR between June 2018 and June 2019. We stratified patients according to the surgical approach: 2-port VATS, 3-port VATS, and subxiphoid VATS. We extracted demographic and clinicopathologic data. We used univariate analysis with unpaired t tests and χ2 tests to compare these variables between the subgroups. RESULTS: We included 201 patients in the analysis. When patients were stratified by surgical approach, there was no difference in terms of age, disease load, length of surgery, postoperative complications, duration of pleural drainage, and length of hospital stay. Postoperative pain and morphine equivalent usage were also comparable between the groups. According to these results, number and location of VATS ports seemingly has no clinical impact on early postoperative outcomes. Limitations of the study include its retrospective nature, small sample size, and short follow-up interval. CONCLUSION: Our results suggest that incision location and the number of VATS ports is not associated with differences in the incidence of perioperative complications or postoperative pain. Given the limitations described above, further studies with longer follow-up intervals are required to explore the lasting impact of this surgical approach on quality of life.

Early risk factors for prolonged mechanical ventilation in patients with severe blunt thoracic trauma: A retrospective cohort study.

BACKGROUND: A significant proportion of patients with severe chest trauma require mechanical ventilation (MV). Early prediction of the duration of MV may influence clinical decisions. We aimed to determine early risk factors for prolonged MV among adults suffering from severe blunt thoracic trauma. METHODS: This retrospective, single-center, cohort study included all patients admitted between January 2014 and December 2020 due to severe blunt chest trauma. The primary outcome was prolonged MV, defined as invasive MV lasting more than 14 days. Multivariable logistic regression was performed to identify independent risk factors for prolonged MV. RESULTS: The final analysis included 378 patients. The median duration of MV was 9.7 (IQR 3.0-18.0) days. 221 (58.5 %) patients required MV for more than 7 days and 143 (37.8 %) for more than 14 days. Male gender (aOR 3.01, 95 % CI 1.63-5.58, p < 0.001), age (aOR 1.40, 95 % CI 1.21-1.63, p < 0.001, for each category above 30 years), presence of severe head trauma (aOR 3.77, 95 % CI 2.23-6.38, p < 0.001), and transfusion of >5 blood units on admission (aOR 2.85, 95 % CI 1.62-5.02, p < 0.001) were independently associated with prolonged MV. The number of fractured ribs and the extent of lung contusions were associated with MV for more than 7 days, but not for 14 days. In the subgroup of 134 patients without concomitant head trauma, age (aOR 1.63, 95 % CI 1.18-2.27, p = 0.004, for each category above 30 years), respiratory comorbidities (aOR 9.70, 95 % CI 1.49-63.01, p = 0.017), worse p/f ratio during the first 24 h (aOR 1.55, 95 % CI 1.15-2.09, p = 0.004), and transfusion of >5 blood units on admission (aOR 5.71 95 % CI 1.84-17.68, p = 0.003) were independently associated with MV for more than 14 days. CONCLUSIONS: Several predictors have been identified as independently associated with prolonged MV. Patients who meet these criteria are at high risk for prolonged MV and should be considered for interventions that could potentially shorten MV duration and reduce associated complications. Hemodynamically stable, healthy young patients suffering from severe thoracic trauma but no head injury, including those with extensive lung contusions and rib fractures, have a low risk of prolonged MV.

A Novel Urine Test Biosensor Platform for Early Lung Cancer Detection.

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection is essential to achieving a better outcome and prognosis. Volatile organic compounds (VOCs) reflect alterations in the pathophysiology and body metabolism processes, as shown in various types of cancers. The biosensor platform (BSP) urine test uses animals' unique, proficient, and accurate ability to scent lung cancer VOCs. The BSP is a testing platform for the binary (negative/positive) recognition of the signature VOCs of lung cancer by trained and qualified Long-Evans rats as biosensors (BSs). The results of the current double-blind study show high accuracy in lung cancer VOC recognition, with 93% sensitivity and 91% specificity. The BSP test is safe, rapid, objective and can be performed repetitively, enabling periodic cancer monitoring as well as an aid to existing diagnostic methods. The future implementation of such urine tests as routine screening and monitoring tools has the potential to significantly increase detection rate as well as curability rates with lower healthcare expenditure. This paper offers a first instructive clinical platform utilizing VOC's in urine for detection of lung cancer using the innovative BSP to deal with the pressing need for an early lung cancer detection test tool.

The 8th Edition TNM Stage Reclassification of T4 Non-Small Cell Lung Cancer: A Granular Examination of Short and Long-Term Outcomes.

INTRODUCTION: Whilst the American Joint Committee on Cancer 7th edition (AJCC7) classified pT4 non-small-cell lung cancers (NSCLC) as those with extra-pulmonary invasion, the revised 8th edition (AJCC8) included tumors > 7cm regardless of extra-pleural spread. We examined perioperative and long-term outcomes of classical T4 definitions with patients whose tumors were greater than 7cm without extra-pulmonary invasion. MATERIALS AND METHODS: A retrospective single center cohort study was performed. All consecutive patients with pT4 lesions between 2011 and 2018 were identified based on either the AJCC7 or AJCC8 classification. Clinicopathological variables were extracted and compared in a univariate manner. A multivariate Cox regression analysis was performed to assess factors associated with overall survival. RESULTS: Forty patients were allocated to AJCC7 and 118 to AJCC8. Patients in the former were more likely to have positive lymph nodes, synchronous metastasis, multifocal disease and lymphovascular invasion. AJCC7 patients were more likely to undergo pneumonectomy despite significantly more being treated with neoadjuvant therapy. Ninety-day mortality was higher in the AJCC7 group. There was no difference in long-term overall survival. On multivariate analysis male gender, squamous cell histology and increasing tumor size were associated with an increased risk of death. CONCLUSION: Although long-term outcomes were similar, the heterogenicity within the AJCC8 classification emphasizes the need to contextualize the perioperative outcomes for patients with pT4 NSCLC. These data are important for future iterations of the TNM classification in view of emerging neoadjuvant options for patients with cT4 operable NSCLC.

Relation between mismatch repair status, chemoresponse, survival and anatomic location in gastroesophageal adenocarcinoma.

BACKGROUND: It has recently been reported that mismatch repair (MMR) status and microsatellite instability (MSI) status in gastroesophageal carcinomas predict surgical, chemotherapeutic and immunotherapeutic outcomes; however, there is extensive variability in the reported incidence and clinical implications of MMR/MSI status in gastroesophaegal adenocarcinomas. We characterized a Canadian surgical patient cohort with respect to MMR status, clinicopathologic correlates and anatomic tumour location. METHODS: We investigated MMR and BRAF V600E status of gastroesophaegal adenocarcinomas in patients who underwent gastrectomy or esophagectomy with extended (D2) lymphadenectomy at a single centre between 2011 and 2019. We correlated patterns of MMR expression in the overall cohort and in anatomic location-defined subgroups with treatment response and overall survival using multivariate analysis. RESULTS: In all, 226 cases of gastroesophaegal adenocarcinoma (63 esophageal, 98 gastroesophageal junctional and 65 gastric) were included. The MMR-deficient (dMMR) immunophenotype was found in 28 tumours (12.3%) (15 junctional [15.3%], 13 gastric [20.0%] and none of the esophageal). The majority (25 [89%]) of dMMR cases showed MLH1/PMS2 loss without concurrent BRAF V600E mutation. Two MSH2/ MSH6-deficient gastric tumours and 1 MSH6-deficient junctional tumour were detected. The pathologic response to preoperative chemotherapy was comparable in the dMMR and MMR-proficient (pMMR) cohorts. However, dMMR status was associated with significantly longer median overall survival than pMMR status (5.8 yr v. 2.4 yr, hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.06-3.46), particularly in junctional tumours (4.6 yr v. 1.9 yr, HR 2.97, 95% CI 1.27-6.94). CONCLUSION: Our study shows that MMR status has at least prognostic value, which supports the need for biomarker testing in gastroesophageal adenocarcinomas, including junctional adenocarcinomas. This highlights the clinical significance of determining the MMR status in all adenocarcinomas of the upper gastrointestinal tract. Response to induction chemotherapy, however, was not influenced by MMR status.

A novel, accurate, and non-invasive liquid biopsy test to measure cellular immune responses as a tool to diagnose early-stage lung cancer: a clinical trials study.

INTRODUCTION: Lung cancer remains the leading cause of death from cancer, worldwide. Developing early detection diagnostic methods, especially non-invasive methods, is a critical component to raising the overall survival rate and prognosis for lung cancer. The purpose of this study is to evaluate two protocols of a novel in vitro cellular immune response test to detect lung cancer. The test specifically quantifies the glycolysis metabolism pathway, which is a biomarker for the activation level of immune cells. It summarizes the results of two clinical trials, where each deploys a different protocol's version of this test for the detection of lung cancer. In the later clinical trial, an improved test protocol is applied. METHOD: The test platform is based on changes in the metabolic pathways of the immune cells following their activation by antigenic stimuli associated with Lung cancer. Peripheral Blood Mononuclear Cells are loaded on a multiwell plate together with various lung tumor associated antigens and a fluorescent probe that exhibits a pH-dependent absorption shift. The acidification process in the extracellular fluid is monitored by a commercial fluorescence plate reader device in continuous reading for 3 h at 37 °C to document the fluorescent signal received from each well. RESULTS: In the later clinical trial, an improved test protocol was applied and resulted in increased test accuracy. Specificity of the test increased to 94.0% and test sensitivity increased to 97.3% in lung cancer stage I, by using the improved protocol. CONCLUSION: The improved protocol of the novel cellular immune metabolic response based test detects stage I and stage II of lung cancer with high specificity and sensitivity, with low material costs and fast results.

Long-Term Quality of Life After Esophagectomy for Esophageal Cancer.

BACKGROUND: Surgery, as part of a multimodal approach, offers the greatest chance of cure for esophageal cancer. However, esophagectomy is often perceived as having a lasting impact on quality of life (QOL), biasing some physicians and patients toward nonoperative management. A comprehensive understanding of the dynamic changes in patient-centered outcomes is therefore important for decision making. Our objective was to determine the long-term QOL after esophagectomy. METHODS: Data were obtained from a prospectively collected (2006-2015) esophagectomy database at a high-volume center, and patients surviving 3 or more years were identified. Health-related QOL was evaluated using the Functional Assessment of Cancer Therapy-Esophageal Module (FACT-E) at diagnosis and every 3 to 6 months, and was stratified according to operative approach, stage, and complications. In addition, QOL scores were compared with normative population values. RESULTS: Of 480 patients, 47% (n = 226) survived 3 or more years and 70% (158 of 226) completed the health-related QOL assessments. Time of follow-up was 5.1 ± 2.8 years. After a reduction at 1 to 3 months, FACT-E increased from a baseline of 126 (95% CI, 121-131) to 133 (95% CI, 127-139) at 12 months, and to 147 (95% CI, 142-153) by 5 years. There was no difference in long-term FACT-E with respect to the surgical approach, clinical and pathologic stage, or postoperative complications. At long-term follow-up (more than 3 years), QOL did not differ significantly from the normative population reference values. CONCLUSIONS: The long-term QOL of esophagectomy patients surviving at least 3 years is improved when compared with the time of diagnosis and does not differ from the general population.

Evaluation of deployment capability of a novel outside-the-scope, detachable catheter system for ablation of lung lesions in ex vivo human lung models.

Objectives: Effective transbronchial ablation of lung nodules requires precise catheter delivery to the target lesion and freedom from the bronchoscope for safety throughout the procedure and to allow for multiple catheter insertions. A fully detachable, outside-the-scope (OTS) probe system was developed that attaches to a flexible bronchoscope. Using this system, the operator can deploy the probe in the target and completely detach it from the scope. Our aim was to demonstrate the endobronchial deployment accuracy and feasibility of an OTS, detachable, simulated ablation catheter driven to peripheral lung targets in ex vivo-ventilated human lung models. Methods: A balloon catheter inflated with radiopaque contrast was used as a simulated peripheral target in freshly explanted lungs from lung transplant recipients. A simulated ablation catheter was positioned outside and aligned to the tip of the bronchoscope using the OTS system. Under fluoroscopic guidance, the bronchoscope and the catheter were driven toward the target in mechanically ventilated lungs. Once the catheter tip was confirmed within the target, the OTS system was released and the probe was detached from the scope. The bronchoscope was retracted and fluoroscopy was used to confirm the position of the catheter. Results: Twelve peripheral targets were simulated. The ablation catheter was successfully deployed with its tip positioned within 5 mm from the target and confirmed stability during multiple cycles of ventilation. Conclusions: A novel, detachable, OTS system can be successfully deployed in peripheral lung targets with potential clinical applications for multiple procedures in advanced bronchoscopy where scope freedom is advantageous.

ERAS 2.0: Continued Refinement of an Established Enhanced Recovery Protocol for Esophagectomy.

BACKGROUND: We have previously demonstrated that implementing an enhanced recovery protocol (ERP) improved outcomes after esophagectomy. We sought to examine if, after a decade of an established ERP, further improvements in postoperative outcomes could be made after continually optimizing and revising the pathway. METHODS: Patients undergoing esophagectomy for cancer from January 2019 to January 2020 were compared with our early-experience group within the initial ERP (June 2010-May 2011) and pre-ERP traditional care (June 2009-May 2010). The original ERP was initiated on June 2010 and underwent several revisions from 2014 to 2018, incorporating the following, amongst other elements: shorten the planned length of stay from 7 to 6 days, elimination of nasogastric tubes, use of soft closed-suction chest drains, and increased application of minimally invasive esophagectomy (MIE). Thirty-day outcomes (complications, length of stay, readmission) were compared for patients undergoing esophagectomy during the initial and most recent ERPs. RESULTS: Overall, 175 patients were identified; 47 underwent esophagectomy before ERP implementation (traditional care), 59 patients underwent esophagectomy after implementation of the original ERP, and 69 patients underwent esophagectomy after the most recent ERP (ERP 2.0). The groups were similar with respect to age, sex, and diagnosis. There were three times more MIEs in the ERP 2.0 group with a shorter median length of stay (7 [6-9] vs. 8 [7-17] vs. 10 [9-17]; p < 0.001) without impacting postoperative morbidity or readmission rate. CONCLUSION: Continued evaluation of institutional outcomes after esophagectomy should be performed to identify target areas for optimization and revision of established enhanced recovery protocols. ERPs are dynamic processes that can be further refined to yield greater improvements in outcomes.

Patient derived xenografts (PDX) predict an effective heparanase-based therapy for lung cancer.

Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient. We have previously shown that heparanase levels are substantially elevated in lung cancer, correlating with reduced patients survival. Applying patient-derived lung cancer xenografts and a potent inhibitor of heparanase enzymatic activity (PG545) we investigated the significance of heparanase in the pathogenesis of lung cancer. PG545 was highly effective in lung cancer PDX, inhibiting tumor growth in >85% of the cases. Importantly, we show that PG545 was highly effective in PDX that did not respond to conventional chemotherapy (cisplatin) and vice versa. Moreover, we show that spontaneous metastasis to lymph nodes is markedly inhibited by PG545 but not by cisplatin. These results reflect the variability among patients and strongly imply that PG545 can be applied for lung cancer therapy in a personalized manner where conventional chemotherapy fails, thus highlighting the potential benefits of developing anti-heparanase treatment modalities for oncology.

Erratum to: caustic ingestion management: world society of emergency surgery preliminary survey of expert opinion.

[This corrects the article DOI: 10.1186/s13017-015-0043-4.].

Caustic ingestion management: world society of emergency surgery preliminary survey of expert opinion.

Caustic material ingestion injuries (CMI) are uncommon. Only 5,000 cases are reported in the United States each year and most acute care healthcare facilities admit only a few cases annually. Accordingly, no single institution can claim extensive experience, and management protocols are most probably based on either expert opinion or literature reports. In this study, we will attempt to review opinions and practices of representatives of the board members of the World Society of Emergency Surgery and compare them to the current literature.

Pediatric invasive Haemophilus influenzae infections in Israel in the era of Haemophilus influenzae type b vaccine: a nationwide prospective study.

BACKGROUND: The conjugated Haemophilus influenzae (Hi) type b vaccine caused a marked decrease in invasive Hi disease rates. Nonencapsulated Hi infection now constitutes most invasive Hi morbidity and mortality. This study examines invasive Hi infection incidence in Israel in the postvaccine era years, 2003-2012, and characterizes the epidemiology, clinical diagnosis and case fatality rates of invasive Hi disease in children <15 years of age. METHODS: An ongoing, nationwide prospective surveillance program for invasive Hi infections in Israel. Epidemiologic and clinical data were collected. Diagnoses were classified as meningitis, pneumonia, bacteremia/sepsis and other clinical foci. RESULTS: Overall, 389 cases of invasive Hi infections were identified; 242 (62%) nontypable Hi (NTHi), 103 (26%) Hi type b (Hib) and 41 (11%) encapsulated non-b Hi (enbHi). Children <1 year of age accounted for 51% of the overall disease. Invasive Hi disease incidence in children <15 years of age was stable with a mean annual incidence (per 100,000) of 2.0 ± 0.4. The highest incidence of invasive Hi infections was among infants <1 year with rates of 6.2, 4.9, 1.6 and 12.7 for NTHi, Hib, enbHi and total Hi, respectively. The clinical diagnoses of NTHi and enbHi were similar, but differed from Hib with the former presenting mostly as isolated sepsis/bacteremia and the latter primarily as meningitis. Among children with invasive Hib infection, 40% were classified as vaccine failure. CONCLUSIONS: In the post-Hib vaccination era, invasive Hi morbidity and mortality are largely attributed to NTHi sepsis. Still, with the changing epidemiology of invasive Hi, continued surveillance of all Hi strains is justified.