Identification of epigenetic silencing of the SFRP2 gene in colorectal cancer as a clinical biomarker and molecular significance.

BACKGROUND: Several studies have suggested secreted frizzled-related protein 2 (SFRP2) gene as a potential clinical biomarker in colorectal cancer (CRC). However, its diagnostic role remains unclear. In this study, we aimed to investigate the significance of SFRP2 methylation levels in a large cohort of biological specimens (including blood, adipose and colonic tissues) from patients with CRC, thereby potentially identifying new biomarker utility. METHODS: We examined the expression (by qPCR) and methylation status (by 450 K DNA array and DNA pyrosequencing) of the SFRP2 gene in healthy participants (N = 110, aged as 53.7 (14.2), 48/62 males/females) and patients with CRC (N = 85, aged 67.7 (10.5), 61/24 males/females), across different biological tissues, and assessing its potential as a biomarker for CRC. Additionally, we investigated the effect of recombinant human SFRP2 (rhSFRP2) as a therapeutic target, on cell proliferation, migration, and the expression of key genes related to carcinogenesis and the Wnt pathway. RESULTS: Our findings revealed that SFRP2 promoter methylation in whole blood could predict cancer stage (I + II vs. III + IV) (AUC = 0.653), lymph node invasion (AUC = 0.692), and CRC recurrence (AUC = 0.699) in patients with CRC (all with p < 0.05). Furthermore, we observed a global hypomethylation of SFRP2 in tumors compared to the adjacent area (p < 0.001). This observation was validated in the TCGA-COAD and TCGA-READ cohorts, demonstrating overall hypermethylation (both with p < 0.001) and low expression (p < 0.001), as shown in publicly available scRNA-Seq data. Notably, neoadjuvant-treated CRC patients exhibited lower SFRP2 methylation levels compared to untreated patients (p < 0.05) and low promoter SFRP2 methylation in untreated patients was associated with poor overall survival (p < 0.05), when compared to high methylation. Finally, treatment with 5 µg of rhSFRP2 treatment in CRC cells (HCT116 cells) inhibited cell proliferation (p < 0.001) and migration (p < 0.05), and downregulated the expression of AXIN2 (p < 0.01), a gene involved in Wnt signaling pathway. CONCLUSIONS: These findings establish promoter methylation of the SFRP2 gene as a prognostic candidate in CRC when assessed in blood, and as a therapeutic prognostic candidate in tumors, potentially valuable in clinical practice. SFRP2 also emerges as a therapeutic option, providing new clinical and therapeutical avenues.

8-Oxoguanine DNA Glycosylase 1 Upregulation as a Risk Factor for Obesity and Colorectal Cancer.

DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)-a DNA repair enzyme-may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of OGG1 expression in CRC participants (p < 0.005) and a downregulation of OGG1 in normal-weight healthy patients (p < 0.05). Interestingly, the methylation analysis showed the hypermethylation of OGG1 in CRC patients (p < 0.05). Moreover, expression patterns of OGG1 were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that OGG1 can regulate CRC risk through obesity and may act as a biomarker for CRC.

C reactive protein as a predictor of anastomotic leakage in colorectal surgery. Comparison between open and laparoscopic surgery. / Proteína C reactiva como predictor de fuga anastomótica en cirugía colorrectal. Comparación entre cirugía abierta y laparoscópica.

INTRODUCTION: Anastomotic leak (AL) is a serious complication in colorectal surgery due to its increase in morbidity and mortality. The aim of this prospective non-randomised study is to determine whether C-reactive Protein (CRP) is useful as a predictor of AL in patients undergoing open versus laparoscopic surgery. METHODS: A total of 168 patients undergoing elective colorectal surgery were included. CRP was measured daily during the first 5postoperative days. Complications, specially AL, were analysed. RESULTS: Following an open approach 32 patients (45.7%) presented complications, 15 (18.7%) in the laparoscopic group and 12 (29.4%) in the converted group (P=0.153). Following open surgery 9 patients experienced AL, 5 were detected in the laparoscopic group and none in those converted (P=0.153). There were significant differences in CRP values between the 3 groups (P=0.03). ROC Curves showed AUC for the open and laparoscopic approach of 0.731 and 0.760 respectively. On day 4 the AUC was 0.867 for the open group and 0.914 for the laparoscopic group. Cut-off points on day 4 were: Open: 159.2mg/L; sensitivity 75%, specificity 89% and NPP 96% (P<0.001). Following laparoscopic surgery the cut-off point was 67.3%; sensitivity 100%, specificity 89.5% and NPP 100% (P=0.016). CONCLUSION: CRP on day 4 is useful to diagnose AL. Different cut-off values should be taken into account depending on the approach used.

Association Between Concurrent Use of Benzodiazepines and Opioids and Health Care Utilization Among Patients With Cancer in Puerto Rico.

PURPOSE: To evaluate the association between concurrent use of opioids and benzodiazepines (BZDs) and emergency room (ER) visits and hospital admissions in patients with cancer. METHODS: Data were obtained from the Puerto Rico Central Cancer Registry-Health Insurance Linkage. Odds ratios (ORs) with 95% CIs and incidence rate ratio (IRR) were estimated using logistic and negative binomial regression analyses to assess the association between concurrent use of opioids and BZDs (overlap of at least 7 days) and ER visits and hospital admissions. RESULTS: A total of 9,259 patients were included in the main analysis. The logistic regression results showed a significant association between concurrent use of opioids and BZDs and at least one ER visit (OR, 1.28 [95% CI, 1.07 to 1.54]) or hospital admission (OR, 1.42 [95% CI, 1.18 to 1.71]) compared with individuals with BZDs alone, after adjusting for age, sex, comorbidity index, cancer stage, health insurance, and health region. Compared with individuals with opioid use alone, the association did not reach significance. In the negative binomial regression, a significant association was observed for ER visits (IRR, 1.52 [95% CI, 1.31 to 1.76]) and hospitalizations (IRR, 1.34 [95% CI, 1.20 to 1.50]) when compared with individuals with BZDs alone. Compared with individuals with opioids alone, it only reached significance for ER visits (IRR, 1.39 [95% CI, 1.20 to 1.61]). CONCLUSION: Careful evaluation must be done before prescribing concurrent opioids and BZDs in patients with cancer, as the results suggest that coprescribing may increase the odds of ER visits and hospitalizations.

Patterns of End-of-Life Care as Measured by Emergency Room Visits Among Cancer Patients in Puerto Rico.

BACKGROUND: Community palliative care (PC) services are scarce in Puerto Rico (PR). Patients with advanced cancer commonly visit the emergency department(ED) at the end of life (EoL). Recognition of patients with limited life expectancies and PC needs may improve the EoL trajectory of these patients. Our objective was to characterize ED visits of cancer patients at the EoL by examining the patterns of ED visits in PR using the PR Central Cancer Registry-Health Insurance Linkage Database (PRCCR-HILD). METHODS: The cohort consisted of patients aged ≥18 years with a primary invasive that died between 2011- 2017, with a recorded date of death, and who had insurance claims during their last three months. EoL indicators were ED visits, ED death, and hospice care use. RESULTS: The study cohort included 10,755 cancer patients. 49.6% had ≥1 ED visit, 20.3% had ≥2 ED visits, and 9.7% died in the ED. In the adjusted model, female patients (aOR 0.80; 95% CI 0.68-0.93; p-value < 0.01), patients aged ≥80 years (aOR 0.47; 95% CI 0.36-0.63; p-value < 0.01), being enrolled in Medicare (aOR 0.74; 95% CI 0.61-0.90; p-value < 0.01) or being enrolled in Medicaid/Medicare (aOR 0.76; 95% CI 0.62-0.93; p-value = 0.01) were less likely to have an ED visit the date of death. Patients with distant stage are more likely to have ED ≥ 2visits (p-value < 0.05). Conclusions: ED visits at EoL can be interpreted as poor quality cancer care and awareness of the potential of ED-initiated PC is needed in PR.

Laparoscopic and hand-assisted liver resection: preliminary results at a mid-sized hospital.

BACKGROUND/AIMS: Laparoscopic liver resection is controversial, specially for tumors. The aim of our study is to report our initial experience. METHODOLOGY: From October 2004 to October 2008, 15 patients underwent laparoscopic liver resection at our institution. RESULTS: Fifteen laparoscopic surgeries were performed on 15 patients. Five patients with hepatocellular carcinoma (HCC), six patients presented liver metastasis and four patients were diagnosed of hydatid cyst. In the HCC group two laparoscopic left lateral segmentectomies and 3 laparoscopic atypical resections were performed. Mean operative time was 230 minutes (95%CI 171-289). In the liver metastasis group six laparoscopic resections were performed. Two patients were converted to open surgery. The laparoscopic procedures were: 2 hand-assisted right hepatectomies, 1 left lateral segmentectomy and 1 atypical resection. The mean surgical time was 257.5 minutes, (95%CI 198-317). In the hydatid cyst group 4 laparoscopic surgeries were performed: three pericystectomies and one partial cystectomy. The mean operative time was 133.75 minutes, (95%CI 68-200). No re-operations were needed and no post-operative deaths occurred. In oncological resections surgical margins were free of tumor in all cases. CONCLUSION: When liver laparoscopic surgery is performed in selected patients, it may offer similar results to conventional surgery with all the benefits of the minimal invasive procedures.

Matrix metalloproteinase-9 as a marker for acute ischemic stroke: a systematic review.

Matrix metalloproteinase-9 (MMP-9) is a possible marker for acute ischemic stroke (AIS). In animal models of cerebral ischemia, MMP expression was significantly increased and was related to blood-brain barrier disruption, vasogenic edema formation, and hemorrhagic transformation. The definition of the exact role of MMPs after ischemic stroke will have important diagnostic implications for stroke and for the development of therapeutic strategies aimed at modulating MMPs. The objectives of the present study were to determine (1) whether MMP-9 is a possible marker for AIS; (2) whether MMP-9 levels correlate with infarct volume, stroke severity, or functional outcome; and (3) whether MMP-9 levels correlate with the development of hemorrhagic transformation after tissue plasminogen activator (t-PA) administration. The literature was searched using MEDLINE and EMBASE with no year restriction. All relevant reports were included. A total of 22 studies (3,289 patients) satisfied the inclusion criteria. Our review revealed that higher MMP-9 values were significantly correlated with larger infarct volume, severity of stroke, and worse functional outcome. There were significant differences in MMP-9 levels between patients with AIS and healthy control subjects. Moreover, MMP-9 was a predictor of the development of intracerebral hemorrhage in patients treated with thrombolytic therapy. MMP-9 level was significantly increased after stroke onset, with the level correlating with infarct volume, stroke severity, and functional outcome. MMP-9 is a possible marker for ongoing brain ischemia, as well as a predictor of hemorrhage in patients treated with t-PA.

High-Intensity End-of-Life Care Among Patients With GI Cancer in Puerto Rico: A Population-Based Study.

PURPOSE: High-intensity care with undue suffering among patients with cancer at the end of life (EoL) is associated with poor quality of life. We examined the pattern and predictors of high-intensity care among patients with GI cancer in Puerto Rico. METHODS: This population-based study of data from the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database examined patients with GI cancer who died between 2009 and 2017. EoL care intensity indicators include the following services in the last month before death: emergency room (ER) visits, hospitalizations, intensive care unit (ICU) admissions, life-extending procedures, death in an acute care setting, and the use of chemotherapy in the last 14 days. We used logistic regression models to examine factors associated with EoL care. RESULTS: Four thousand six hundred twenty-nine patients with GI cancer were included in the analysis. We found that 11.0% of patients received chemotherapy, 17.3% had > 1 hospitalization, 9.3% were in the ICU, 18.0% had > 1 ER visit, 39.3% died in an acute care setting, and 8.6% received life-extending procedures. A compound indicator of the aggressiveness of care showed that 54.5% of patients had at least one of the selected aggressive indicators. The multivariable model showed that female patients, patients ≥ 60 years of age, patients enrolled in Medicaid, patients dually eligible for both Medicare and Medicaid, and patients who survived > 1 year were less likely to receive aggressive EoL care. CONCLUSION: Our findings support the urgent need to improve EoL care in Puerto Rico. Further studies are warranted to fully understand EoL care in patients with cancer in Puerto Rico.

Evaluation and management of renal colic in the emergency department.

Renal stones (nephrolithiasis) are a relatively common problem and a frequent Emergency Department (ED) diagnosis in patients who present with acute flank/abdominal pain. The goal of this topic review is to provide physicians with an evidence-based diagnostic approach for the evaluation and management of patients with nephrolithiasis. Unenhanced helical CT scan of the abdomen and pelvis should be performed on all patients with their first episode of acute flank pain and suspected renal colic. It is considered the optimal diagnostic test to confirm a urinary stone in a patient with flank pain. Pain management can be achieved by using NSAIDs, opioids or a combination of both. Several factors will help you determine if emergent urology evaluation is warranted; size and location of renal calculi, persistence of colic pain, impaired renal function and signs of infection.

Fecal incontinence in older patients. A narrative review. / Incontinencia fecal en el paciente anciano. Revisión de conjunto.

Fecal incontinence is one of the leading causes for the institutionalization of people in the last decades of life, associated with a great psychosocial and economic burden. The literature is scarce in this population group, due to the absence of universally accepted criteria to define "elderly patients" and difficulties in detection and diagnostic. The aim of this article was to conduct a narrative review of the main aspects related to fecal incontinence in older patients, providing management support. Toileting assistance, dietary change, controlling stool consistency and medical treatment can be used to treat these patients. Nevertheless, other therapies, such as biofeedback, neuromodulation or surgical treatment, can be considered in selected patients.

Critical urologic skills and procedures in the emergency department.

The evaluation and management of genitourinary emergencies is a fundamental component of the training and practice of emergency physicians. Urologic procedures are common in the emergency room. Emergency physicians play a vital role in the initial evaluation and treatment because delays in management can lead to permanent damage. This article discusses the most common urologic procedures in which emergency physicians must be proficient for rapid intervention to preserve function and avoid complications. An overview of each procedure is discussed as well as indications, contraindications, equipment, technique, and potential complications.