Oxidative Stress and DNA Damage Markers in Colorectal Cancer.

Oxidative stress (OS) and inflammation are known to play an important role in chronic diseases, including cancer, and specifically colorectal cancer (CRC). The main objective of this study was to explore the diagnostic potential of OS markers in patients with CRC, which may translate into an early diagnosis of the disease. To do this, we compared results with those in a group of healthy controls and assessed whether there were significant differences. In addition, we explored possible correlations with the presence of tumors and tumor stage, with anemia and with inflammatory markers used in clinical practice. The study included 80 patients with CRC and 60 healthy controls. The following OS markers were analyzed: catalase (CAT), reduced glutathione (GSH) and oxidized glutathione (GSSG) in serum; and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and F2-isoprotanes in urine (F2-IsoPs). Tumor markers (CEA and CA 19.9), anemia markers (hemoglobin, hematocrit and medium corpuscular volume) and inflammatory markers (leukocytes, neutrophils, N/L index, platelets, fibrinogen, C-reactive protein, CRP and IL-6) were also determined. Comparison of means between patients and controls revealed highly significant differences for all OS markers, with an increase in the prooxidant markers GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and a decrease in the antioxidant markers CAT and GSH. Tumor and inflammatory markers (except CRP) correlated positively with GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and negatively with CAT and GSH. In view of the results obtained, OS markers may constitute a useful tool for the early diagnosis of CRC patients.

The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer.

The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.

Surgical Wound Complications after Colorectal Surgery with Single-Use Negative-Pressure Wound Therapy Versus Surgical Dressing over Closed Incisions: A Randomized Controlled Trial.

BACKGROUND: Global studies indicate that surgical site infections (SSIs) are a major healthcare challenge within hospitals and can have a profound impact on patient quality of life and healthcare costs. Closed-incision negative-pressure therapy (ciNPT) has been reported to provide positive clinical benefits for patients with various incisions, including those following colorectal surgeries. METHODS: Investigators performed a prospective, randomized, multicenter trial to evaluate complications of surgical incisions in patients who received a ciNPT dressing versus a conventional surgical dressing (control) over their closed incision following colorectal surgery. The incidence of SSI was determined at 7, 15, and 30 days postsurgery. RESULTS: A total of 148 patients participated in the study. Results showed that the SSI rate on day 7 was lower in the ciNPT group versus the control group (10/75 [13.3%] vs 17/73 [23.3%]), but this difference was not statistically significant. On day 15, the SSI rate was 12/75 (16.0%) in the ciNPT group versus 21/73 (28.8%) in the control group; however, this difference was only marginally statistically significant (P = .0621). At 1 month, the SSI rate remained lower in the ciNPT group (13/75 [17.3%] vs 21/73 [28.8%], P = .0983) compared with the control group. CONCLUSIONS: Future studies with larger population sizes are necessary to determine the impact of ciNPT on patients' incisions after colorectal surgery.

Laparoscopic staged colon-first resection for metastatic colorectal cancer: Perioperative and midterm outcomes from a single-center experience.

INTRODUCTION: The present study aimed to evaluate the short- and mid-term outcomes of laparoscopic colon-first staged resection for colorectal cancer (CRC) and colorectal cancer liver metastases (CRCLM). METHODS: This study included patients with metastatic CRC who underwent laparoscopic surgical staged resection for the primary tumor and CRCLM between June 2013 and December 2018. Data collection included the baseline patient's and tumor features, the perioperative and histopathologic outcomes from both surgical procedures, and the oncologic follow-up. RESULTS: Twenty-five patients were eligible for the study. Three major and 22 minor laparoscopic liver resections were performed following laparoscopic CRC surgery. Five patients required conversion to laparotomy during CRCLM resection, but no conversion was needed for the colorectal procedures. The rate of severe intraoperative complications (CLASSIC grade III-IV) was 8% and 16% during CRC and CRCLM resection, respectively. Three patients (12%) developed major postoperative complications (Clavien-Dindo grade > III) after both interventions, including one death due to intraoperative bleeding. During a median follow-up of 30 months, 15 patients were diagnosed with disease recurrence. The 3-year disease-free survival and overall survival were 33.3% and 73.9%, respectively. CONCLUSIONS: Laparoscopic staged resection for CRC and CRCLM is safe, feasible, and offers acceptable midterm oncological outcomes in patients with metastatic colorectal cancer.

Radioguided detection of a non-palpable occult lesion (ROLL) in a case of abdominal metastasis of a neuroendocrine tumor.

Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms that originate in tissues derived from the neural crest, whose characteristic feature is the expression of neuroendocrine markers and somatostatin receptors. Here, we present the case of a patient with a surgically intervened small bowel NET. Focal uptake was identified in the unresected mesentery in the scintigraphy of somatostatin receptors (99mTc-Tektrotyd). A second intervention was performed with intraoperative radio-guided detection with a gamma probe and a handheld SPECT. An intraoperative radioguided technique allowed the detection of a lesion that was confirmed by histology to be a lymph node metastasis of the NET and a nodule of NET in the anastomosis of the first surgical intervention.

Robotic, transanal, and laparoscopic total mesorectal excision for locally advanced mid/low rectal cancer: European multicentre, propensity score-matched study.

BACKGROUND: Total mesorectal excision (TME) is the standard surgery for low/mid locally advanced rectal cancer. The aim of this study was to compare three minimally invasive surgical approaches for TME with primary anastomosis (laparoscopic TME, robotic TME, and transanal TME). METHODS: Records of patients undergoing laparoscopic TME, robotic TME, or transanal TME between 2013 and 2022 according to standardized techniques in expert centres contributing to the European MRI and Rectal Cancer Surgery III (EuMaRCS-III) database were analysed. Propensity score matching was applied to compare the three groups with respect to the complication rate (primary outcome), conversion rate, postoperative recovery, and survival. RESULTS: A total of 468 patients (mean(s.d.) age of 64.1(11) years) were included; 190 (40.6%) patients underwent laparoscopic TME, 141 (30.1%) patients underwent robotic TME, and 137 (29.3%) patients underwent transanal TME. Comparative analyses after propensity score matching demonstrated a higher rate of postoperative complications for laparoscopic TME compared with both robotic TME (OR 1.80, 95% c.i. 1.11-2.91) and transanal TME (OR 2.87, 95% c.i. 1.72-4.80). Robotic TME was associated with a lower rate of grade A anastomotic leakage (2%) compared with both laparoscopic TME (8.8%) and transanal TME (8.1%) (P = 0.031). Robotic TME (1.4%) and transanal TME (0.7%) were both associated with a lower conversion rate to open surgery compared with laparoscopic TME (8.8%) (P < 0.001). Time to flatus and duration of hospital stay were shorter for patients treated with transanal TME (P = 0.003 and 0.001 respectively). There were no differences in operating time, intraoperative complications, blood loss, mortality, readmission, R0 resection, or survival. CONCLUSION: In this multicentre, retrospective, propensity score-matched, cohort study of patients with locally advanced rectal cancer, newer minimally invasive approaches (robotic TME and transanal TME) demonstrated improved outcomes compared with laparoscopic TME.

The role of oxidative stress, tumor and inflammatory markers in colorectal cancer patients: A one-year follow-up study.

Oxidative stress (OS) and inflammation are known to play an important role in colorectal cancer (CRC). This study analyzed tumor, inflammatory and OS markers in CRC patients and in a control group. In addition, the evolution of these markers was evaluated after one-year of follow-up treatment. This was a longitudinal and prospective, observational study in 80 CRC patients who were candidates for tumor resection surgery and/or chemo-radiotherapy treatment and a healthy control group (n = 60). Subsequently, catalase (CAT), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSSG/GSH ratio in serum and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and F2-IsoProstanes (F2-IsoPs) in urine at 1, 6 and 12 months after treatment was analyzed. Tumor markers (CEA and CA 19.9), as well as inflammatory markers-leukocytes, neutrophils, neutrophil/lymphocyte (N/L) index, platelets, fibrinogen, C-reactive protein (CRP), and interleukin 6 (IL6)- were also analyzed. As expected, levels of CEA and CA 19.9 and markers of inflammation, except CRP, were significantly higher in CRC compared to the control group. Regarding OS markers, a decrease in CAT and GSH and an increase in GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs were found in CRC patients compared to healthy controls at baseline. After treatment, an improvement of their inflammation profile was accompanied by a progressive recovery of antioxidant enzyme activities and the decline of oxidative byproducts both in serum and urine. Based on the results obtained, we propose the assay of urinary 8-oxodG and F2-IsoPs, as well as serum CAT, GSH, GSSG as a marker for the evaluation of OS and the clinical follow-up of CRC patients.

How to strengthen the management of acute diverticulitis: the utility of the WSES classification-a prospective single-center observational study.

PURPOSE: This study aimed to validate the World Society for Emergent Surgery (WSES) scale for the management of acute left-sided colonic diverticulitis (ALCD). METHODS: An observational study based on a prospective database of patients with ultrasound (US) and computerized tomography (CT) confirmed ALCD was conducted at our center from April 2018 to May 2019. The primary outcome was the success rate of outpatient management. Secondary outcomes were the association between different WSES stages, clinical and analytical parameters, treatments modalities, and outcomes, and the accuracy of US for management decisions. RESULTS: A total of 230 patients were included. Outpatient management was successful in 51/53 (96.23%) cases with ALCD stage 0 and 62/72 (86.11%) patients with stage 1A. There were no differences in age (p = 0.076) or the presence of pericolic air bubbles (p = 0.06) between patients who underwent admission or outpatient management. Clinical and analytical data, treatment decisions, and outcomes showed statistically significant differences between WSES stages. In 7/12 patients with stage 2A, percutaneous drainage or emergency surgery was required. All cases with stage 2B (distant air) underwent conservative management without the need for emergency or elective surgery. The accuracy of US WSES stages for management decisions, when compared with CT, was 96.96%. CONCLUSION: The WSES classification for ALCD seemed to be valid helping clinicians in the decision-making process to select between admission or outpatient management. Differences in clinical and analytical data, elected treatments, and outcomes were found between WSES stages. The US WSES stages showed high accuracy for management decisions.

Adherence to the Mediterranean Diet Has a Protective Role against Metabolic and DNA Damage Markers in Colorectal Cancer Patients.

Oxidative stress (OS) and inflammation have been related to colorectal cancer (CRC), but the influence of the Mediterranean diet (MD) on these parameters is unknown. Therefore, the aim of this study was to determine the association between adherence to the MD and markers of OS and DNA damage in CRC patients and to study the influence of adherence to the MD on metabolic and tumor-related factors. This prospective observational study included a total of 80 patients diagnosed with CRC. Adherence to the MD was estimated by the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire. The levels of OS markers (catalase, glutathione peroxidase, and glutathione system in serum; 8-oxo-7'8-dihydro-2'-deoxyguanosine and F2-isoprotanes in urine) and tumor and metabolic factors were determined. A total of 51.2% of our CRC patients showed a high adherence to the MD. These patients presented decreased levels of 8-oxodG, increased GPX and HDL-cholesterol levels, and a downward trend in the GSSG/GSH ratio with respect to patients with low adherence to the MD. In addition, a high adherence to the MD was associated with a lower histological grade of the tumor and a lower presence of synchronous adenomas. We conclude that a high adherence to the MD has a protective role against metabolic and oxidative DNA damage and improves antioxidant systems in CRC patients.

Roux-en-Y Gastric Bypass Modulates AMPK, Autophagy and Inflammatory Response in Leukocytes of Obese Patients.

Obesity is characterized by low-grade chronic inflammation, metabolic overload, and impaired endothelial and cardiovascular function. Roux-en-Y gastric bypass (RYGB) results in amelioration of the pro-oxidant status of leukocytes and the metabolic profile. Nevertheless, little is known about the precise mechanism that drives systemic and metabolic improvements following bariatric surgery. In this cohort study, we investigated the effect of RYGB on molecular pathways involving energy homeostasis in leukocytes in 43 obese subjects one year after surgery. In addition to clinical and biochemical parameters, we determined protein expression of systemic proinflammatory cytokines by Luminex®, different markers of inflammation, endoplasmic reticulum (ER) stress, autophagy/mitophagy by western blot, and mitochondrial membrane potential by fluorescence imaging. Bariatric surgery induced an improvement in metabolic outcomes that was accompanied by a systemic drop in hsCRP, IL6, and IL1ß levels, and a slowing down of intracellular inflammatory pathways in leukocytes (NF-κB and MCP-1), an increase in AMPK content, a reduction of ER stress (ATF6 and CHOP), augmented autophagy/mitophagy markers (Beclin 1, ATG5, LC3-I, LC3-II, NBR1, and PINK1), and a decrease of mitochondrial membrane potential. These findings shed light on the specific molecular mechanisms by which RYGB facilitates metabolic improvements, highlighting the relevance of pathways involving energy homeostasis as key mediators of these outcomes. In addition, since leukocytes are particularly exposed to physiological changes, they could be used in routine clinical practice as a good sensor of the whole body's responses.

Impact of Roux-en-Y Gastric Bypass on Mitochondrial Biogenesis and Dynamics in Leukocytes of Obese Women.

The chronic low-grade inflammation widely associated with obesity can lead to a prooxidant status that triggers mitochondrial dysfunction. To date, Roux-en-Y gastric bypass (RYGB) is considered the most effective strategy for obese patients. However, little is known about its molecular mechanisms. This interventional study aimed to investigate whether RYGB modulates oxidative stress, inflammation and mitochondrial dynamics in the leukocytes of 47 obese women at one year follow-up. We evaluated biochemical parameters and serum inflammatory cytokines -TNFα, IL6 and IL1ß- to assess systemic status. Total superoxide production -dHe-, mitochondrial membrane potential -TMRM-, leucocyte protein expression of inflammation mediators -MCP1 and NF-kB-, antioxidant defence -GPX1-, mitochondrial regulation-PGC1α, TFAM, OXPHOS and MIEAP- and dynamics -MFN2, MNF1, OPA1, FIS1 and p-DRP1- were also determined. After RYGB, a significant reduction in superoxide and mitochondrial membrane potential was evident, while GPX1 content was significantly increased. Likewise, a marked upregulation of the transcription factors PGC1α and TFAM, complexes of the oxidative phosphorylation chain (I-V) and MIEAP and MFN1 was observed. We conclude that women undergoing RYGB benefit from an amelioration of their prooxidant and inflammatory status and an improvement in mitochondrial dynamics of their leukocytes, which is likely to have a positive effect on clinical outcome.

Ultrasound can differentiate complicated and noncomplicated acute colonic diverticulitis: a prospective comparative study with computed tomography.

OBJECTIVE: To prospectively assess the diagnostic value of intestinal ultrasound (US) compared to computerized tomography (CT) in differentiating uncomplicated and complicated acute colonic diverticulitis (ACD). MATERIALS AND METHODS: During a period of 14 months patients referred to the department of Radiology with clinical suspicion of ACD underwent an US examination. All confirmed US ACD diagnosis were included and subsequently underwent an emergency abdominal CT, used as gold standard. The WSES (World Society for Emergent Surgery) classification of diverticulitis was used. Diverticulitis was prospectively classified as either uncomplicated or complicated. Sensitivity, specificity, positive predictive value, and negative predictive values of US were evaluated. Before CT scan, the radiologist indicated whether they would have required or not a complementary CT scan, based on US findings. RESULTS: Of the 240 patients included in our study, 71 (29.6%) were Stage 0, 127 (53%) Stage 1A, and 42 (17.5%) were moderate-severe ACD (stages 1B, 2A, 2B, 3 and 4). The sensitivity of US for diagnosing complicated ACD was 84% and specificity of 95.8%. Most patients (24 of 27) misclassified by US as uncomplicated diverticulitis were classified on CT as stage 1A. From the 148 cases in which the radiologist considered CT unnecessary, only 3 of these revealed signs of complicated ACD on CT; none of them required emergency surgery. CONCLUSION: US is an effective technique to differentiate complicated from uncomplicated ACD. Our results suggest that US, may be a valuable alternative to CT for the initial radiologic evaluation in patients with clinical suspicion of ACD.

The Potential Link between Episodes of Diverticulitis or Hemorrhoidal Proctitis and Diets with Selected Plant Foods: A Case-Control Study.

Diverticulitis and hemorrhoidal proctitis in the population are significant public health problems. We studied the potential association between the intake of certain plant foods and diverticulitis or hemorrhoidal episodes through a case-control study including 410 cases and 401 controls. We used a semiquantitative food frequency questionnaire. The intake was additionally quantified according to a 24 h recall. The plant foods or derived food products were categorized by their main chemical components into ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods such as curcumin. The mean score for overall intake of plant foods under consideration was 6.3 points, and this was significantly higher in cases (8.5) than in controls (4.1). Overall intake was similar in cases presenting with diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (>7 points), compared to controls. Explanatory logistic regression models showed that the strongest association with diverticulitis and hemorrhoidal proctitis was shown by the chemical food group of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. Neither alliin nor miscellaneous food groups showed any association. High, frequent consumption of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids increase the risk of diverticulitis and hemorrhoidal proctitis.

Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin.

Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1ß and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.

Effect of Roux-en-Y Bariatric Bypass Surgery on Subclinical Atherosclerosis and Oxidative Stress Markers in Leukocytes of Obese Patients: A One-Year Follow-Up Study.

Little is known about the mechanisms underlying the cardioprotective effect of Roux en-Y gastric bypass (RYGB) surgery. Therefore, the aim of the present study was to investigate whether weight loss associated with RYGB improves the oxidative status of leukocytes and ameliorates subclinical atherosclerotic markers. This is an interventional study of 57 obese subjects who underwent RYGB surgery. We determined biochemical parameters and qualitative analysis of cholesterol, leukocyte and systemic oxidative stress markers -superoxide production, glutathione peroxidase 1 (GPX1), superoxide dismutase (SOD) activity and protein carbonylation-, soluble cellular adhesion molecules -sICAM-1 and sP-selectin-, myeloperoxidase (MPO) and leukocyte-endothelium cell interactions-rolling flux, velocity and adhesion. RYGB induced an improvement in metabolic parameters, including hsCRP and leukocyte count (p < 0.001, for both). This was associated with an amelioration in oxidative stress, since superoxide production and protein carbonylation were reduced (p < 0.05 and p < 0.01, respectively) and antioxidant systems were enhanced (GPX1; p < 0.05 and SOD; p < 0.01). In addition, a significant reduction of the following parameters was observed one year after RYGB: MPO and sICAM (p < 0.05, for both), sPselectin and pattern B of LDL particles (p < 0.001, for both), and rolling flux and adhesion of leukocytes (p < 0.05 and p < 0.01, respectively). Our results suggest that patients undergoing RYGB benefit from an amelioration of the prooxidant status of leukocytes, metabolic outcomes, and subclinical markers of atherosclerosis.

Laparoscopic management of gastric perforation secondary to mesenteroaxial volvulus in a patient with laparoscopic adjustable gastric banding.

A 54-year-old woman was admitted to the emergency department with a 2-week history of alimentary vomiting. She had undergone laparoscopic adjustable gastric banding 6 years earlier. CT revealed a mesenteroaxial gastric volvulus and ischemia on the gastric wall. Emergent diagnostic laparoscopy was performed, and severe peritonitis and gastric necrosis caused by volvulation was found. After band removal, a fundal perforation was noted, but a viable lesser curvature enabled laparoscopic sleeve gastrectomy to be performed. The postoperative course was uneventful. Laparoscopic adjustable gastric banding is considered a safe and effective method for the surgical treatment of obesity, but it is associated with a number of complications, such as pouch dilatation and band slippage. Although infrequent, ischemic complications are life-threatening conditions that require urgent surgery. This is the first report of this unusual complication managed laparoscopically.

Pinitol alleviates systemic inflammatory cytokines in human obesity by a mechanism involving unfolded protein response and sirtuin 1.

BACKGROUND & AIMS: It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in human obesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). METHODS: In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the ex vivo study, a biopsy of VAT and SAT was removed from thirty-four obese patients and incubated with D-pinitol for 48 h. RESULTS: The consumption of a PEB reduced circulating levels of IL6 and TNFα and increased SIRT1 protein expression in PBMCs. Ex vivo experiments showed a decline in gene expression and protein levels of IL6 and TNFα in SAT and a reduction in ER stress parameters (ATF6 and CHOP), while VAT markers remained unaltered. Differential gene expression profiles revealed an up-regulation of SIRT1 and insulin-signaling pathways in SAT with respect to VAT. CONCLUSIONS: Our results suggests that pinitol down-regulates the inflammatory pathway which may lead to novel treatment options for obesity and its metabolic disorders.