Side-specific factors for intraoperative hemodynamic instability in laparoscopic adrenalectomy for pheochromocytoma: a comparative study.

BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.

Comparative study of laparoscopic ventral mesh rectopexy versus perineal stapler resection for external full-thickness rectal prolapse in elderly patients: enhanced outcomes and reduced recurrence rates-a retrospective cohort study.

BACKGROUND: In elderly patients with external full-thickness rectal prolapse (EFTRP), the exact differences in postoperative recurrence and functional outcomes between laparoscopic ventral mesh rectopexy (LVMR) and perineal stapler resection (PSR) have not yet been investigated. METHODS: We conducted a retrospective multicenter study on 330 elderly patients divided into LVMR group (n = 250) and PSR (n = 80) from April 2012 to April 2019. Patients were evaluated before and after surgery by Wexner incontinence scale, Altomare constipation scale, and patient satisfaction questionnaire. The primary outcomes were incidence and risk factors for EFTRP recurrence. Secondary outcomes were postoperative incontinence, constipation, and patient satisfaction. RESULTS: LVMR was associated with fewer postoperative complications (p < 0.001), lower prolapse recurrence (p < 0.001), lower Wexner incontinence score (p = 0.03), and lower Altomare's score (p = 0.047). Furthermore, LVMR demonstrated a significantly higher surgery-recurrence interval (p < 0.001), incontinence improvement (p = 0.019), and patient satisfaction (p < 0.001) than PSR. Three and 13 patients developed new symptoms in LVMR and PSR, respectively. The predictors for prolapse recurrence were LVMR (associated with 93% risk reduction of recurrence, OR 0.067, 95% CI 0.03-0.347, p = 0.001), symptom duration (prolonged duration was associated with an increased risk of recurrence, OR 1.131, 95% CI 1.036-1.236, p = 0.006), and length of prolapse (increased length was associated with a high recurrence risk (OR = 1.407, 95% CI = 1.197-1.655, p < 0.001). CONCLUSIONS: LVMR is safe for EFTRP treatment in elderly patients with low recurrence, and improved postoperative functional outcomes. TRIAL REGISTRATION: Clinical Trial.gov (NCT05915936), retrospectively registered on June 14, 2023.

Epstein-Barr Virus Promotes Tumorigenicity and Worsens Hodgkin Lymphoma Prognosis by Activating JAK/STAT and NF-κB Signaling Pathways.

Background: Epstein-Barr virus (EBV) is detected in 40% of patients with Hodgkin lymphoma (HL). During latency, EBV induces epigenetic alterations to the host genome and decreases the expression of pro-apoptotic proteins. The present study aimed to evaluate the expression levels of mRNA molecules and the end product of proteins for the JAK/STAT and NF-κB pathways, and their association with clinicopathological and prognostic parameters in patients with EBV-positive and -negative classical Hodgkin lymphoma (CHL). Methods: A prospective cohort study was conducted from 2017 to 2022 at the Faculty of Medicine, Zagazig University Hospital (Zagazig, Egypt). Biopsy samples of 64 patients with CHL were divided into EBV-positive and EBV-negative groups. The expression levels of mRNA molecules (JAK2, STAT1, IRF-1, PD-L1, IFN-γ, NF-κB, Bcl-xL, COX-2) and the end product of proteins (PD-L1, Bcl-xL, COX-2) were determined and compared with clinicopathological and prognostic parameters. Data were analyzed using the Chi square test and Kaplan-Meier estimate. Results: EBV-positive CHL patients were significantly associated with positive expression of mRNAs molecules (P<0.001) and the end product of proteins (P<0.001) for the JAK/STAT and NF-κB pathways, B-symptoms (P=0.022), extra-nodal involvement (P=0.017), and advanced stage of CHL (P=0.018). These patients were more susceptible to cancer progression, higher incidence of relapse (P=0.008), poor disease-free survival rate (P=0.013), poor overall survival rate (P=0.028), and higher mortality rate (P=0.015). Conclusion: Through the activation of JAK/STAT and NF-κB signaling pathways, EBV-positive CHL is associated with poor clinicopathological parameters, higher incidence of disease progression, relapse, and poor overall survival. A preprint of this manuscript is available on research square (doi: 10.21203/rs.3.rs-1857436/v1).

Immunohistochemical Expression of Immune Checkpoints; CTLA-4, LAG3, and TIM-3 in Cancer Cells and Tumor-infiltrating Lymphocytes (TILs) in Colorectal Carcinoma.

BACKGROUND: Colorectal cancer is considered the third most prevalent cancer in both sexes. Immune checkpoint receptors that regulate T-cell response, stimulation, and development include lymphocyte activating gene 3 (LAG-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (Tim-3). In addition, they are crucial for the advancement of cancer and tumor immune escape. OBJECTIVE: This work's aim was to assess the immunohistochemistry expression of Tim-3, CTLA-4, and LAG-3 in cancer cells and tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) and the correlation between these markers and clinicopathological variables and survival data. METHODS: This study involved 206 CRC specimens processed for CTLA-4, LAG3, and TIM-3 immunohistochemistry and correlated with the clinicopathological and survival parameters of the patients. RESULTS: High CTLA-4 epithelial expression was highly related to the old age group, large tumor size, low tumor-stroma ratio (TSR), high grade, advanced stage, the presence of distant metastasis (DM), perineural invasion (PNI), necrosis, lymphovascular invasion (LVI), relapse, mortality, overall survival (OS), and disease-free survival (DFS), while negative CTLA-4 TILs expression was highly linked with the presence of gross perforation, low TSR, high tumor budding (TB) score, high grade, advanced stage, the existence of lymph node (LN) metastasis, DM, necrosis, LVI, PNI, DFS, mortality, and OS. Positive LAG-3 TILs expression was highly correlated with large tumor size, gross perforation, low TSR, high TB score, high grade, advanced phase, the presence of LN, necrosis, LVI, PNI, relapse DFS, mortality, and OS. High Tim-3 epithelial expression was extremely linked with low TSR, advanced phase, the presence of LN, LVI, PNI, relapse, DFS, mortality, and OS, while positive Tim-3 TILs expression was related to gross perforation, low TSR, high TB score, advanced stage, the presence of LN, DM, necrosis, relapse, DFS, mortality, and OS. CONCLUSIONS: The patients' poor prognosis may be related to the immunohistochemistry expression of LAG-3, Tim-3, and CTLA-4 in CRC cancer tissue and TILs. Poor patient consequences can result from the CTLA-4, Tim-3, and LAG-3 co-expression, but CTLA-4 TILs' expression of these proteins may inhibit the growth of tumors.

Intraoperative endomanometric laparoscopic Nissen fundoplication improves postoperative outcomes in large sliding hiatus hernias with severe gastroesophageal reflux disease: a retrospective cohort study.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the gold standard surgical intervention for gastroesophageal reflux disease (GERD). LNF can be followed by recurrent symptoms or complications affecting patient satisfaction. The aim of this study is to assess the value of the intraoperative endomanometric evaluation of esophagogastric competence and pressure combined with LNF in patients with large sliding hiatus hernia (>5 cm) with severe GERD (DeMeester score >100). MATERIALS AND METHODS: This is a retrospective, multicenter cohort study. Baseline characteristics, postoperative dysphagia and gas bloat syndrome, recurrent symptoms, and satisfaction were collected from a prospectively maintained database. Outcomes analyzed included recurrent reflux symptoms, postoperative side effects, and satisfaction with surgery. RESULTS: Three hundred sixty patients were stratified into endomanometric LNF (180 patients, LNF+) and LNF alone (180 patients, LNF). Recurrent heartburn (3.9 vs. 8.3%) and recurrent regurgitation (2.2 vs. 5%) showed a lower incidence in the LNF+ group ( P =0.012). Postoperative score III recurrent heartburn and score III regurgitations occurred in 0 vs. 3.3% and 0 vs. 2.8% cases in the LNF+ and LNF groups, respectively ( P =0.005). Postoperative persistent dysphagia and gas bloat syndrome occurred in 1.75 vs. 5.6% and 0 vs. 3.9% of patients ( P =0.001). Score III postoperative persistent dysphagia was 0 vs. 2.8% in the two groups ( P =0.007). There was no redo surgery for dysphagia after LNF+. Patient satisfaction at the end of the study was 93.3 vs. 86.7% in both cohorts, respectively ( P =0.05). CONCLUSIONS: Intraoperative high-resolution manometry and endoscopic were feasible in all patients, and the outcomes were favorable from an effectiveness and safety standpoint.

Circulating methylated RUNX3 and SFRP1 genes as a noninvasive panel for early detection of colorectal cancer.

OBJECTIVE: This study was conducted to assess the methylation status of runt-related transcription factor 3 (RUNX3) and secreted frizzled-related protein 1 (SFRP1) genes in paired tissue and serum samples of colorectal cancer (CRC), adenomatous, and control subjects and elucidate the association between methylation status on RUNX3 and SFRP1 mRNA expression. METHODS: Methylation status of RUNX3 and SFRP1 in paired tissue and serum samples and RUNX3 and SFRP1 mRNA expression in tissue from 85 patients with CRC, 40 with adenoma, and 40 healthy controls were determined using methylation-specific PCR and reverse transcription PCR. RESULTS: The frequency RUNX3 and SFRP1 genes methylation was significantly higher in both tissues and serum of CRC patients and was significantly associated with absence of its corresponding mRNA expression. The concordance between tissue and serum methylation status was 94.4% for RUNX3 and 94.3% for SFRP1. Tissue RUNX3 methylation status detected CRC with 63.53% sensitivity and 80.00% specificity, while serum RUNX3 methylation status detected CRC with 60.00% sensitivity and 82.50% specificity. Tissue SFRP1 methylation status showed a sensitivity of 82.35% and specificity of 65.00%, while serum SFRP1 methylation status showed a sensitivity of 77.65% and specificity of 70.00% in detection of CRC. RUNX3/SFRP1/carcinoembryonic antigen (CEA) panel identified CRC with sensitivity of 89.41% in tissue and 84.71% in serum. CONCLUSION: Our results verified the reliability of using serum RUNX3 and SFRP1 methylation status as a noninvasive biomarker for diagnosis of CRC and that combined detection of RUNX3/SFRP1/CEA panel might be a promising strategy for early detection of CRC.

Coronary artery bypass grafting experience in the setting of an anomalous origin of the right coronary artery from the left sinus of Valsalva: Midterm results.

BACKGROUND: An anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva with an interarterial course is a rare congenital anomaly. We aimed to assess midterm results after coronary artery bypass grafting (CABG) for the treatment of anomalous RCA arising from the left sinus of Valsalva. METHODS: From 2008 to 2012, 16 patients underwent CABG for treatment of an anomalous origin of the RCA from the left sinus of Valsalva. Details such as risk factors, operative details, and results of multislice coronary angiography follow-up were assessed. RESULTS: The mean age of the patients was 34.8 ± 4.68 years, and most of them were male (15 out of 16, 93.75%). They received a mean of 1.5 ± 0.87 grafts. Closure of the RCA was completed in all patients except one (15 out of 16), who developed ischemic symptoms upon closing the proximal part of the RCA. One in-hospital death occurred. Among the remaining patients, symptoms persisted in 2 out of 15. The mean follow-up time was 63.4 ± 28.6 months. All patients had patent vessels on 5-year follow-up multislice computed tomography scans, except one patient who showed RCA graft occlusion on the 1-year follow-up scan. CONCLUSION: The CABG of the RCA with anomalous origin can be done safely with excellent early and midterm results. Proximal RCA ligation is an essential step to the success of CABG, but intraoperative challenge testing is required to confirm the sufficiency of the internal thoracic artery graft to reperfuse the supplied territory.

Genetic and epigenetic modifications of adiponectin gene: Potential association with breast cancer risk.

BACKGROUND: Adipokines produced by adipose tissue are directly linked to obesity and may contribute to the pathogenesis of cancer. We hypothesized that genetic and epigenetic modifications in the adiponectin (ADIPOQ) gene and their impact on serum ADIPOQ levels may participate in increasing breast cancer (BC) risk. The present study aimed to investigate ADIPOQ +45 T/G gene polymorphism, methylation status at CpG sites -74 nucleotides (nt) and -283 nt of the ADIPOQ gene, and ADIPOQ serum levels in BC obese women. METHODS: Serum ADIPOQ was measured by an enzyme-linked immunosorbent assay. ADIPOQ +45 T/G gene polymorphism and ADIPOQ promoter methylation status were determined using a polymerase chain reaction (PCR) and a methylation-specific PCR, respectively, in 120 obese women with BC and 120 age-matched controls. RESULTS: ADIPOQ +45 GG genotype carriers had a significant increased risk of developing BC (odds ratio = 6.2, 95% confidence interval = 1.3-29.6, p = 0.02). ADIPOQ gene methylation at site -74 nt resulted in a 1.7-fold increased BC risk. Methylation at site -283 nt resulted in a 1.9-fold increased BC risk. Moreover serum levels of ADIPOQ were significantly decreased in BC patients and down-regulated in the presence of methylation in both examined sites. By contrast, no association between ADIPOQ gene polymorphism and serum ADIPOQ level was detected. Using both methylated sites in one panel detected cancer breast with 76.67% sensitivity and 62.18% accuracy. CONCLUSIONS: ADIPOQ +45 T/G polymorphism and ADIPOQ promoter methylation were found to be associated with BC risk in obese Egyptian women.