Comprehensive Peri-Operative Risk Assessment and Management of Geriatric Patients.

Background: As the population ages, the prevalence of surgical interventions in individuals aged 65+ continues to increase. This poses unique challenges due to the higher incidence of comorbidities, polypharmacy, and frailty in the elderly population, which result in high peri-operative risks. Traditional preoperative risk assessment tools often fail to accurately predict post-operative outcomes in the elderly, overlooking the complex interplay of factors that contribute to risk in the elderly. Methods: A literature review was conducted, focusing on the predictive value of CGA for postoperative prognosis and the implementation of perioperative interventions. Results: Evidence shows that CGA is a superior predictive tool compared to traditional models, as it more accurately identifies elderly patients at higher risk of complications such as postoperative delirium, infections, and prolonged hospital stays. CGA includes assessments of frailty, sarcopenia, nutritional status, cognitive function, mental health, and functional status, which are crucial in predicting post-operative outcomes. Studies demonstrate that CGA can also guide personalized perioperative care, including nutritional support, physical training, and mental health interventions, leading to improved surgical outcomes and reduced functional decline. Conclusions: The CGA provides a more holistic approach to perioperative risk assessment in elderly patients, addressing the limitations of traditional tools. CGA can help guide surgical decisions (e.g., curative or palliative) and select the profiles of patients that will benefit from perioperative interventions to improve their prognosis and prevent functional decline.

Postoperative Intravenous Iron Infusion in Anemic Colorectal Cancer Patients: An Observational Study.

Anemia is the most common extraintestinal symptom of colorectal cancer, with a prevalence of 30-75%. While the preoperative anemia in this patient population has been well studied and its correction 4-6 weeks prior to surgery is recommended when feasible, there is a paucity of data regarding the management of postoperative anemia, which has a prevalence of up to 87% in these patients. To address this issue, we conducted an observational cohort study of surgically treated postoperative anemic patients with colorectal cancer. The objective of this study was to evaluate the effect of intravenous ferric carboxymaltose on the correction of postoperative anemia by postoperative day 30 (POD30). The primary outcome was the change in hemoglobin on POD30, while the secondary outcomes were the change in iron and other laboratory parameters, postoperative complications and transfusions. The results demonstrated that patients treated with intravenous iron exhibited a significant increase in hemoglobin levels by POD30, along with a concomitant increase in hematocrit, ferritin, and transferrin saturation levels, compared to the control group. The findings imply that patients undergoing colorectal cancer surgery with anemia that was not corrected in the preoperative setting may benefit from early postoperative intravenous iron infusion.

Precision Oncology: Circulating Microvesicles as New Biomarkers in a Very Early Stage of Colorectal Cancer.

BACKGROUND: The release of microvesicles (MVs) is an essential phenomenon for inter-cellular signaling in health and disease. The role of MVs in cancer is multidimensional and includes cancer cell survival, proliferation, and invasion. In this prospective study, we analyzed MV levels in colorectal cancer patients and assessed the importance of MV release in early-stage colorectal cancer and survival. METHODS: This study included 98 patients and 15 controls. The characterization of MVs from human plasma was performed by flow cytometry using monoclonal antibodies. RESULTS: The levels of total MVs and MUC-1-positive, tissue factor (TF)-positive, and endothelial cell-derived MVs (EMVs) were statistically significantly higher in the colon cancer patients than in the controls (p < 0.001). Furthermore, the subgroup of patients with very early-stage colorectal cancer also had statistically significant differences in the levels of the abovementioned MVs compared to the controls (p < 0.01). Highly differentiated tumors had lower levels of MUC-1-positive MVs (p < 0.02), EMVs (p < 0.002), and EMV/TF combinations (p < 0.001) versus those with tumors with low/intermediate differentiation. CONCLUSIONS: Our data demonstrate that the analysis of circulating MV levels in plasma could possibly become a tool for the early diagnosis of colon cancer at a very early stage of the disease.

Effectiveness and safety of darvadstrocel in patients with complex perianal fistulizing Crohn's disease: a systematic review.

Background: Managing complex perianal fistulizing Crohn's disease (CD) remains challenging, despite current medical and surgical treatment approaches. Darvadstrocel, a therapy utilizing adipose-derived stem cells, shows promise in promoting tissue regeneration and healing, offering a novel and effective treatment for fistula management. Method: A systematic literature search was conducted on PubMed and Scopus to identify studies involving patients with complex perianal fistulizing CD treated with darvadstrocel. Results: In total, 2 randomized controlled trials (RCT), 5 observational studies with retrospective data collection and 2 observational studies with prospective design were included in the final review. Data from the European ADMIRE-CD RCT demonstrated that darvadstrocel is superior to placebo in terms of clinical and imaging improvement over both the short and long term. These findings align with the prospective studies analyzed in this systematic review. The rate of treatment-emergent adverse events in the ADMIRE-CD trial's RCTs was similar in both the darvadstrocel and control groups, with perianal abscess being the most common adverse event up to 52 weeks after drug administration. Retrospective studies indicated no side-effects beyond 52 weeks. Conclusions: Darvadstrocel appears to be a new, potentially effective and safe treatment option for the management of complex perianal fistulas. However, more randomized clinical trials are needed to evaluate the efficacy and safety profile of the drug.

Surgical Treatment of Solitary Metachronous Adrenal Metastasis from Urothelial Carcinoma of the Urinary Bladder.

Urothelial cancer is a common neoplasm and metastatic disease correlates with a poor prognosis. Isolated adrenal gland metastases of urothelial carcinoma are quite rare, and management options can decide a patient's prognosis. Herein we report the case of a 76-year-old man with a metachronous solitary adrenal metastasis from a bladder carcinoma, who underwent adrenalectomy as part of his treatment. Furthermore, we discuss the cases of solitary adrenal metastases of urothelial carcinoma available in the literature, to identify key features to direct appropriate treatment of this rare metastatic site of urothelial cancer and improve prognosis and survival. Still, further prospective studies are needed to design effective therapeutic strategies.

DECIDE: Delphi Expert Consensus Statement on Inflammatory Bowel Disease Dysplasia Shared Management Decision-Making.

BACKGROUND AND AIMS: Inflammatory bowel disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. METHODS: Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders, and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. RESULTS: In all, 31 members [15 gastroenterologists, 14 colorectal surgeons and two nurse specialists] from nine countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. CONCLUSIONS: By consolidating evidence for best practice using literature review and key stakeholder and decision-making expert consultation, we have developed international consensus recommendations to support health care professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

The Inflammatory Bowel Disease-Disk Tool for Assessing Disability in Inflammatory Bowel Disease Patients: Validation of the Greek Version.

BACKGROUND: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. METHODS: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. RESULTS: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86-0.91)]. Cronbach's coefficient alpha for all items achieved 0.90 (95%CI 0.88-0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. CONCLUSIONS: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.

Iron Deficiency Anemia in Colorectal Cancer Patients: Is Preoperative Intravenous Iron Infusion Indicated? A Narrative Review of the Literature.

Iron deficiency anemia is the most common extraintestinal symptom in patients with colorectal cancer (CRC). Inflammation associated with malignancy leads to functional iron deficiency via the hepcidin pathway, whereas chronic blood loss causes absolute iron deficiency and depletion of iron stores. The assessment and treatment of preoperative anemia is of great importance in patients with CRC, since published data have consistently shown that preoperative anemia is associated with increased need for perioperative blood transfusions and more postoperative complications. Recent studies have documented mixed results regarding the preoperative intravenous iron administration in anemic CRC patients in terms of efficacy for anemia correction, cost-effectiveness, need for transfusions and risk for postoperative complications.

Signaling pathways associated with bone loss in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized in many patients by extraintestinal manifestations. One of the most common comorbidities seen in IBD patients is a significant reduction in their bone mass. The pathogenesis of IBD is mainly attributed to the disrupted immune responses in the gastrointestinal mucosa and putative disruptions in the gut microbiomes. The excessive inflammation of the gastrointestinal tract activates different systems, such as the RANKL/RANK/OPG and the Wnt pathways linked with bone alterations in IBD patients, thereby suggesting a multifactorial etiology. The mechanism responsible for the reduced bone mineral density in IBD patients is thought to be multifactorial, and, so far, the principal pathophysiological pathway has not been well established. However, in recent years, many investigations have increased our understanding of the effect of gut inflammation on the systemic immune response and bone metabolism. Here, we review the main signaling pathways associated with altered bone metabolism in IBD.

Specific Neuropeptide Expression in Crohn's Disease Ileocolonic Resection Specimens Is Not Associated with Plexitis at the Ileal Margin or Postoperative Recurrence.

BACKGROUND: Myenteric plexitis is considered a risk factor for postoperative recurrence (POR) in Crohn's disease (CD). The primary purpose of this study was to evaluate the association between neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and substance P (SP) expression and plexitis at the proximal resection margin. The secondary aim was to identify risk factors for POR. METHODS: A retrospective, single-center study on CD patients who underwent ileocolonic resection (ICR) between January 2010 and December 2016 was conducted. The presence and severity of plexitis were evaluated by hematoxylin and eosin stain. Mast cells were highlighted by Giemsa stain. Immunohistochemistry was used to identify T lymphocytes and NPY-, VIP-, and SP-ergic neurons. Neuropeptide expression was quantified using image analysis. RESULTS: Seventy-nine patients were included. No association was detected between NPY, VIP, and SP expression and plexitis. Similarly, the number of involved inflammatory cells, T lymphocytes or mast cells was not correlated with neuropeptide expression. Smoking (hazard ratio [HR] 4.07; 95% confidence interval [CI] 2.08-7.94; p < 0.001), moderate (HR 3.68; 95%CI 1.06-12.73; p = 0.040), and severe myenteric plexitis (HR 7.36; 95%CI 1.12-48.30; p = 0.037) were independent risk factors for endoscopic POR, whereas smoking (HR 2.78; 95%CI 1.01-7.67; p = 0.049), severe myenteric plexitis (HR 20.03; 95%CI 1.09-368.28; p = 0.044), and involved ileal margin (HR 3.45; 95%CI 1.33-8.96; p = 0.011) for clinical POR. CONCLUSIONS: Smoking, moderate or severe myenteric plexitis, and involved ileal margin negatively affect POR in CD patients undergoing ICR. Submucosal and myenteric plexitis at the proximal resection margin is not related to the expression of specific neuropeptides.

Response to Anti-α4ß7 Blockade in Patients With Ulcerative Colitis Is Associated With Distinct Mucosal Gene Expression Profiles at Baseline.

BACKGROUND: Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4ß7, vedolizumab, in patients with active ulcerative colitis (UC). METHODS: Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly. RESULTS: In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a "core" mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade. CONCLUSIONS: Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.

Predictors of Response to Vedolizumab in Patients with Ulcerative Colitis: Results from the Greek VEDO-IBD Cohort.

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.

Experimental Intestinal Stenosis Alters Crohn's Disease-Like Intestinal Inflammation in Ileitis-Prone Mice.

BACKGROUND: Clinical observations indicate that mechanical factors contribute to the expression or recurrence of Crohn's disease. We investigated whether the creation of an intestinal stenosis could alter the severity of the expected Crohn-like ileitis, in a Crohn's disease animal model, the TNFΔare/+ mouse. METHODS: Thirty-six, 6-weeks-old TNFΔare/+ mice, were divided into 3 intervention groups: triple suture, single suture and sham. In the terminal ileum, in the first group, a triple suture stenosis was created, whereas, in the second, a loose suture was placed. Same triple-suture stenosis was performed on twelve wild type mice. All animals were sacrificed at 6 weeks post-operatively and the ileum parts were evaluated histopathologically. A summative total ileitis score was applied in each sample using a bespoke semiquantitative histological scoring system for the Crohn-like changes. RESULTS: The triple suture stenosis induced significant muscular hypertrophy proximal to interventional site which was more prominent in TNFΔare/+ than wild type mice. In triple suture group, the total ileitis score was significantly increased proximal to the intervention as compared to the single suture (P: 0.004) and the sham groups (P: 0.013). The total ileitis score distally, was unaffected, regardless of the experimental intervention. Intestinal stenosis did not induce intestinal inflammation in wild type mice. CONCLUSION: The creation of a stenosis in the terminal ileum of TNFΔare/+ mice alters Crohn-like inflammation. We assume that mechanical forces, such as intraluminal pressure, may contribute as important co-factors to the pathophysiology of Crohn's disease in genetically predisposed subjects.

Inflammatory myoglandular polyp as a cause of recurrent abdominal pain in a patient with quiescent Crohn's disease.

Chronic inflammation of the intestinal mucosa has been associated with the appearance of inflammatory polyps or pseudopolyps. Among the distinct categories of inflammatory polyps are inflammatory myoglandular polyps (IMGP) usually found in the colorectum. Only one case of IMGP in the terminal ileus has been described since their first description. We report the first case of an inflammatory polyp with both hyperplastic and myoglandular histological characteristics, in the terminal ileum of a patient with quiescent Crohn's disease, causing recurrent intussusception.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study.

BACKGROUND: Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece. METHODS: This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively. RESULTS: A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%). CONCLUSIONS: The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.

Effects of Anti-Inflammatory Treatment and Surgical Intervention on Endothelial Glycocalyx, Peripheral and Coronary Microcirculatory Function and Myocardial Deformation in Inflammatory Bowel Disease Patients: A Two-Arms Two-Stage Clinical Trial.

Sixty inflammatory bowel disease (IBD) patients (45 Crohn disease and 15 ulcerative colitis, 40 ± 13 years, 53% male) were examined at baseline and 4 months after intervention (surgical (35 patients) or anti-TNFa treatment (25 patients)). IBD severity, using Mayo score, Harvey-Bradshaw Index (HBI) and biomarkers, was correlated with cardiovascular markers. At baseline, the disease severity, the white blood cells (WBC) values and the reducing power (RP) were significantly correlated with the aortic pulse wave velocity (PWV) (r = 0.4, r = 0.44 and r = 0.48, p < 0.05) and the lateral mitral E' velocity (r = 0.35, p < 0.05 and r = 0.3, p < 0.05). Four months after intervention, there was a reduction of WBC (1962.8/mm3 ± 0.425/mm3, p < 0.001), C-reactive protein (CRP) (8.1 mg/L ± 1.7 mg/L, p < 0.001), malondialdehyde (MDA) (0.81 nmol/mg ± 0.37, p < 0.05) and glycocalyx perfused boundary region (PBR 5-25) (0.24 µm ± 0.05 µm, p < 0.01). Moreover, the brachial flow mediated dilatation (FMD), the coronary flow reserve (CFR) and the left ventricle global longitudinal strain (LV GLS) were significantly improved for both groups (4.5% ± 0.9%, 0.55 ± 0.08, 1.4% ± 0.35%, p < 0.01), while a more significant improvement of PWV/GLS was noticed in the anti-TNFa group. IBD severity is associated with vascular endothelial, cardiac diastolic, and coronary microcirculatory dysfunction. The systemic inflammatory inhibition and the local surgical intervention lead to significant improvement in endothelial function, coronary microcirculation and myocardial deformation.

Clinical evidence, diagnostic approach and challenging therapeutic modalities for malignant melanoma of the anorectum.

Primary anorectal malignant melanoma (ARMM) is a rare, aggressive tumour that accounts for approximately 1.2% of all melanomas. This rare entity represents less than 5% of anorectal malignant tumours and 0.05-1% of all malignant colorectal neoplasms. The incidence increases with age while there is a higher prevalence in Caucasians. ARMM is often asymptomatic or presents with no disease-specific evidence so that it can mimic other rectal disorders, malignant or benign. Colonoscopy is obligatory as a diagnosing mean for ARMM. Furthermore, endoscopic ultrasonography, computed tomography and magnetic resonance imaging can be utilized for the evaluation of tumour infiltration and lymph node metastases. Moreover, diagnostic establishment of ARMM requires an undeniable demonstration of essential melanocytic features in histology and immunohistochemistry. Even though the standard of treatment remains surgical resection, the choice between wide local excision and abdomino-perineal resection is still controversial. Recently, there have been recommendations regarding new techniques which could be utilized for the surgical treatment of ARMM. Newer treatments that have been proposed such as immune-checkpoint inhibitors and targeted therapies need further validation. A multicenter study would allow clarification of the most appropriate therapeutic strategy for this uncommon nosological entity.