Impact of a positive end-expiratory pressure strategy on oxygenation, respiratory compliance, and hemodynamics during laparoscopic surgery in non-obese patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Higher positive end-expiratory pressure (PEEP) during laparoscopic surgery may increase oxygenation and respiratory compliance. This meta-analysis aimed to compare the impact of different intraoperative PEEP strategies on arterial oxygenation, compliance, and hemodynamics during laparoscopic surgery in non-obese patients. METHODS: We searched RCTs in PubMed, Cochrane Library, Web of Science, and Google Scholar from January 2012 to April 2022 comparing the different intraoperative PEEP (Low PEEP (LPEEP): 0-4 mbar; Moderate PEEP (MPEEP): 5-8 mbar; high PEEP (HPEEP): >8 mbar; individualized PEEP - iPEEP) on arterial oxygenation, respiratory compliance (Cdyn), mean arterial pressure (MAP), and heart rate (HR). We calculated mean differences (MD) with 95% confidence intervals (CI), and predictive intervals (PI) using random-effects models. The Cochrane Bias Risk Assessment Tool was applied. RESULTS: 21 RCTs (n = 1554) met the inclusion criteria. HPEEP vs. LPEEP increased PaO2 (+ 29.38 [16.20; 42.56] mmHg, p < 0.0001) or PaO2/FiO2 (+ 36.7 [+ 2.23; +71.70] mmHg, p = 0.04). HPEEP vs. MPEEP increased PaO2 (+ 22.00 [+ 1.11; +42.88] mmHg, p = 0.04) or PaO2/FiO2 (+ 42.7 [+ 2.74; +82.67] mmHg, p = 0.04). iPEEP vs. MPEEP increased PaO2/FiO2 (+ 115.2 [+ 87.21; +143.20] mmHg, p < 0.001). MPEEP vs. LPEP, and HPEEP vs. MPEEP increased PaO2 or PaO2/FiO2 significantly with different heterogeneity. HPEEP vs. LPEEP increased Cdyn (+ 7.87 [+ 1.49; +14.25] ml/mbar, p = 0.02). MPEEP vs. LPEEP, and HPEEP vs. MPEEP did not impact Cdyn (p = 0.14 and 0.38, respectively). iPEEP vs. LPEEP decreased driving pressure (-4.13 [-2.63; -5.63] mbar, p < 0.001). No significant differences in MAP or HR were found between any subgroups. CONCLUSION: HPEEP and iPEEP during PNP in non-obese patients could promote oxygenation and increase Cdyn without clinically significant changes in MAP and HR. MPEEP could be insufficient to increase respiratory compliance and improve oxygenation. LPEEP may lead to decreased respiratory compliance and worsened oxygenation. PROSPERO REGISTRATION: CRD42022362379; registered October 09, 2022.

Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma.

PURPOSE: To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer. METHODS: We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan-Meier analysis and uni- and multivariate Cox regression analysis. RESULTS: Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan-Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS. CONCLUSION: Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.

Draft genome sequence of a Fusobacterium nucleatum strain isolated from a patient in Kazakhstan with colorectal cancer.

Fusobacterium nucleatum is an invasive obligate anaerobe found in the oral microbiota and associated with colorectal cancer. Here, we announce the draft genome sequence of Fusobacterium nucleatum strain Fn11kaz from a patient with colorectal cancer in Kazakhstan.

Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer.

OBJECTIVES: To investigate the predictive impact of the proliferation biomarker Ki-67 on the clinical course of patients with initial stage pTa urothelial carcinoma of the bladder (UCB). METHODS: We retrospectively analyzed all patients treated by transurethral resection of bladder tumors (TUR-B) for UCB between 1992-2004 in a single-center. Disease recurrence (≥pTa UCB) and absent tumor in histopathology, assessed by TUR-B with a non-malignant result for endoscopic suspect bladder lesion displayed endpoints. Immunohistochemical (IHC) analysis of formalin-fixed and paraffin-embedded tissue blocks was performed with an immunostainer using a primary antibody for Ki-67. Semiquantitative evaluation of Ki-67 was performed by three reviewers. Increased proliferation was defined with a cut-off value of ≥50%. Uni- and multivariable binary regression analyses were applied to address prediction of disease recurrence. RESULTS: 215 patients (84% male, median age 69 years at first diagnosis) were evaluable and included to the study. 89 patients stayed disease-free (41%), 126 patients showed recurrence (59%). Recurrence rates of patients with Ki-67 expression <10%, 10-24%, 25-49% and ≥50% were 14.8% vs. 30.8% vs. 63.9% and 80.7%, respectively (p < 0.001). In Kaplan-Meier analysis patients with increased proliferation ≥50% showed a statistically significant worse 10-year recurrence-free survival (19% vs. 57%, p < 0.001). Multivariable regression analysis revealed instillation treatment (p = 0.001) and high proliferation of Ki-67 (p < 0.001) to be independent predictors of recurrence in stage pTa UCB. CONCLUSIONS: High proliferation with Ki-67 expression ≥50% was strongly associated with worse recurrence-free survival in patients with initial stage pTa UCB. Stage pTa UCB patients with increased Ki-67 expression should undergo a strictly follow-up regime comparable to stage pT1 bladder carcinoma, while at least patients with Ki-67 expression <10% might be feasible for more liberate follow-up regime after evaluation of our data in randomized, prospective and multicenter studies.