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.

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.

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.

Experimental Models of Partial Intestinal Obstruction in Young Mice: Establishment, and Evaluation.

BACKGROUND: Partial small bowel obstruction (SBO) is a common, potentially hazardous, surgical entity caused by numerous factors in humans. A number of techniques have been reported as efficient to simulate partial SBO in murine models. However, there is little data concerning their long-term survival. Our study presents a novel technique and evaluates its long-term efficiency compared with other commonly used techniques. MATERIALS AND METHODS: Sixty C57BL/6 mice aged 6 to 8 wk were randomly divided into five intervention groups: ligation, intestinal ring, partial ligation, microclips, and the novel triple suture technique. The ring groups were subdivided into narrow, medium, and wide ring and partial ligation groups were subdivided at 1/3, 1/2, and 2/3 of the lumen. Survival cutoff time was set at 4 wk. Animals were then euthanized and small bowel muscle layer thickness was histopathologically evaluated. RESULTS: None of the animals of the ligation and the ring groups reached the cutoff survival time. The mortality rate of the partial ligation and the microclips groups at the 4-week period were 33.3% and 0%, respectively. However, elimination of the performed intervention was revealed at the time of euthanasia and no alterations of the muscle layer were revealed at histopathology. The "triple suture" group had a survival rate of 90% until euthanasia and the sutures were apparent in all cases. Macroscopic evaluation showed small to mild proximal lumen dilatation in 6 of 10 animals. Histopathological evaluation of the specimens confirmed the partial obstruction. CONCLUSIONS: The "triple suture" technique is a new, robust, reliable, and inexpensive technique for experimental long-standing partial SBO, with very low mortality.

Are radiologic pouchogram and pouchoscopy useful before ileostomy closure in asymptomatic patients operated for ulcerative colitis?

OBJECTIVES: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the "gold standard" procedure for patients with ulcerative colitis (UC) requiring surgical intervention. A de-functioning ileostomy is usually performed, as a step for the IPAA procedure. The aim of this study is to present the methodology and results of the routine double assessment of IPAA integrity in asymptomatic patients prior to the ileostomy reversal and evaluate its necessity. METHODS: This is a retrospective study of 61 UC patients, who underwent IPAA construction, in 2010-2016. A diverting ileostomy was created after IPAA construction, which was reversed at least 3 months later. A double assessment, with pouchogram and pouchoscopy, of IPAA integrity was performed, before stoma closure. Post-operative symptoms and signs of complications, imaging studies, and endoscopic findings were recorded during follow-up. RESULTS: Prior to the ileostomy reversal, both pouchoscopy and pouchogram identified no patient with evidence of anastomotic leakage. During a mean follow-up of 3.67 years after ileostomy reversal, 11 patients developed complications but only one had signs of leakage, which presented as a pouch-vaginal fistula. The specificity of both the pouchogram and pouchoscopy reached 100% and the negative predictive value ranged between 98.4 and 100%. CONCLUSIONS: The specificity of pouchoscopy and pouchogram prior to ileostomy closure, in asymptomatic patients with IPAA for UC, is very high in recognizing an intact anastomosis, but their combination did not alter the diagnostic accuracy or had any effect in further management. At least, pouchogram could be selectively performed only in patients with high-risk clinical indicators. KEY POINTS: • The double assessment of ileal pouch-anal anastomosis with pouchogram and pouchoscopy, prior to ileostomy closure, specifically in patients with ulcerative colitis has not been evaluated before. • The specificity of pouchoscopy and pouchogram prior to ileostomy closure, in asymptomatic patients with IPAA for UC, is very high in recognizing an intact anastomosis. • However, their combination did not alter the diagnostic accuracy or had any effect in further management, in asymptomatic patients.

Perioperative Use of Anti-TNFa Biological Agents in Open and Laparoscopic Surgery for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) consists of two disorders: Crohn's disease (CD) and ulcerative colitis (UC). Over the past few decades, a great body of knowledge has accumulated regarding the pathogenesis of IBD, and effective pharmaceutical agents, such as inhibitors of tumor necrosis factor (anti-TNF), have been introduced. Although these agents have dramatically improved the outcome of IBD, up to 70% of patients with CD and 10-30% of those with UC still undergo surgery within 10 years from diagnosis. Because of their young age and high recurrence rates, these patients are appropriate candidates for laparoscopic surgery as an alternative to laparotomy. Recently, considerable attention has been focused on perioperative outcomes of patients who are receiving anti-TNF agents and require surgery. The aim of this narrative review is to discuss the current evidence regarding the impact of perioperative anti-TNF treatment on post-operative complication rates with a special focus on laparoscopic surgery.

Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Large Paraesophageal Hiatus Hernia: Is Surgery Mandatory?

Purpose/Aim: Paraesophageal hiatus hernias are seldom found, however the incidence is increasing accounting for 5-10% of all hiatal hernias. The aim of this review is to emphasize controversies in clinical presentation, essential workup investigations and highlight non-surgical and surgical management options. Materials and Methods: A PubMed literature search using the keywords "large or giant paraesophageal hernia", "hiatus or hiatal hernia", "laparoscopic surgery", "antireflux surgery", "mesh", "gastric volvulus" and "diaphragmatic hernia" published between 1998 until 2017 was conducted. Results: Presenting symptoms are non-specific and can be erroneously attributed to various more common medical conditions. Significant complications as gastric volvulus and stomach necrosis, may occur and the obscured clinical presentation can be confusing for the clinician. Management options in the elective setting are controversial, and surgical repair cannot be easily justified for a minimally symptomatic condition, especially in an elderly and perhaps frail patient. However, in the era of laparoscopic surgery around the hiatus, reduced operative stress makes surgical repair appealing in the elective setting. Surgical matters as the adjunct of an antireflux procedure or not, the use of prosthetic mesh to reinforce the hiatus, gastropexy and the clinical importance of radiological or endoscopic recurrence are still under debate. Conclusions: The laparoscopic treatment of paraesophageal hiatus hernias is effective with low morbidity rates, offered in symptomatic patients and good operative risk asymptomatic individuals. More studies are needed to assess improvement suggestions, as the use of prosthetic mesh or gastropexy, regarding complications and recurrence risks.

A 12-year experience at a tertiary hospital on patients with multiple primary malignant neoplasms.

PURPOSE: The incidence of multiple primary malignant neoplasms (MPMN) has dramatically increased. The purpose of this retrospective study was to present the 12-year experience at a University Hospital in patients with MPMN and to investigate the role of genetic factors in their pathogenesis. METHODS: The medical records of 7516 cancer patients, treated in our Institution from 2000 to 2012, were reviewed. Diagnosis of MPMN was based on the Warren and Gates' criteria. RESULTS: Among 7516 patients, 39 (0.5%) (10 men, mean age 70.0±6.98 years, and 29 women, mean age 64.7±8.24 years) presented with MPMN. Eighty-two percent of them developed 2 primary malignant neoplasms (PMNs), whereas 3 PMNs were developed in 7 patients. Breast cancer was the most common cancer type diagnosed among female patients (59%); 14 and 3 had 2 and 3 PMNs, respectively. Eight had a family history of breast cancer while in 3 genetic testing revealed mutations in BRCA1 and BRCA2 genes. The second most common type of malignancy was colorectal cancer (24%); 5 developed 2 PMNs, whereas 2 developed 3 PMNs. Five patients had a family history of colorectal cancer. Colon cancer was the most frequent neoplasm among male patients (50%; 3 developed 2 and 2 3 PMNs. In 2 patients the family history was positive for colorectal cancer. CONCLUSIONS: Although many factors may contribute to MPMN development, positive family history and inherent mutations significantly predispose to MPMN appearance. Thus, management of MPMN patients should be based on a detailed family history and genetic testing.

Sporadic versus inflammatory bowel disease-related colorectal adenocarcinoma: lessons learned from a single institution experience.

PURPOSE: Inflammatory bowel disease (IBD) - related colorectal adenocarcinoma (CAC) is known to impose a less favorable prognosis than its sporadic counterpart. The determining factor in the prognosis of IBD patients is the early endoscopic detection of commonly occult pre-cancerous lesions. This retrospective study attempted to highlight the distinctive features of IBD-related CAC, as well as the importance of implementing an acceptable surveillance protocol in IBD patients. METHODS: The medical records and biopsies of all IBD patients undergoing surgery and of surgical patients with sporadic CAC, admitted in the 5-year period 2010-2014, were examined. Overall, 26 clinicopathological parameters were collected and compared between the two groups. RESULTS: A total of 370 patients with sporadic CAC and 103 patients with IBD were included in the study, of which 8.7% (9/103) proved to have CAC. Cancer in IBD patients appeared at a younger age, had a larger maximum diameter and was more likely to have multiple synchronous locations and a signet-ring cell differentiation (p<0.05). Only 25% of IBD patients with CAC had previously followed correct surveillance. CONCLUSIONS: The aggressive features of IBD-related CAC, as well as the rising incidence of poorly-surveilled IBD patients that eventually progress to cancer, reflect the necessity of establishing dedicated IBD centers for their optimal follow-up.

Association of FokI and PvuII polymorphisms with breast cancer staging and survival among Caucasian women: a prospective study.

PURPOSE: Both vitamin D and estrogens play an important role in breast cell growth and differentiation. Therefore, we hypothesized that FokI polymorphism in the Vitamin D Receptor (VDR) gene, as well as PvuII polymorphism in the Estrogen Receptor (ESR) gene might be associated with progression of breast cancer. The aim of this study was to prospectively examine the association of these polymorphisms with histopathological features and prognosis among women with histologically proven breast cancer. METHODS: Patient characteristics, tumor histopathology, and genotyping of one VDR polymorphism variant (FokI) and one ER polymorphism variant (PvuII) were recorded. Patients were also routinely followed up. RESULTS: There was a significant difference regarding nodal stage (p<0.001) between the different genotypes of FokI polymorphisms (FF, Ff, ff), even though a trend was also detected in the frequency between ductal and lobular type, as well as tumor size (p=0.077). When further analysis was performed regarding patients whose polymorphism included the f allele, we found statistically significant differences in tumor size (p<0.001), nodal stage (p=0.03), tumor grade (p=0.04) and lymphovascular invasion (p<0.001), while no differences in nodal status, distant metastases and tumor stage were noticed. No significant associations were found between any of the PvuII polymorphism variants and tumor histopathology and stage. No statistical significance was proven between FokI polymorphism's variants or f allele and overall or progression-free survival. Statistically significant associations between overall and progression- free survival and PvuII polymorphism's variants was demonstrated (p<0.001). CONCLUSION: The f allele was associated with the presence of lymphovascular invasion and poorly differentiated tumors, whereas the PP genotype was associated with increased overall and progression-free survival, suggesting that this variant is related to a more favorable prognosis.

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.

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.

Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance.

MicroRNAs are a class of non-coding molecules found to regulate a variety of cellular functions in health and disease. Dysregulation of microRNAs is involved in liver disease, especially hepatocarcinogenesis. Since primary hepatic malignancies are typically characterized by late diagnosis, frequent recurrence, and poor response to adjuvant therapy, there is a need for the discovery of novel biomarkers in order to achieve earlier diagnosis, predict tumor aggressiveness and response to adjuvant therapy. The purpose of this study is to evaluate the expression of certain microRNAs (miR-21, -31, -122, -145, -146a, - 200c, -221, -222 and -223) in patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as to assess their prognostic significance. Micro-RNA expression was assessed by reverse transcription and real-time PCR (RT-PCR). Clinicopathological data and survival rates were retrieved and analyzed. According to our results, miR-21, miR-31, miR-122, miR-221, miR-222 were significantly up-regulated in HCC tissues, whereas miR-145, miR-146a, miR-200c, and miR-223 were found to be down-regulated. Concerning ICC samples, miR-21, miR-31, and miR-223 were found to be over-expressed, whereas miR-122, miR-145, miR-200c, miR-221, and miR-222 were down-regulated. Additionally, expression of miR-21, miR-31, miR-122, and miR-221 in HCC correlated with cirrhosis, while miR-21 and miR-221 associated with tumor stage and poor prognosis. In ICC tissues, miR-21, miR-31, and miR-223 were found to be over-expressed, but no correlation with clinicopathological features was found.

MicroRNA gene polymorphisms in pancreatic cancer.

MicroRNAs (miRNAs) act as regulators of gene expression via translational repression. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to affect the regulatory capacity of miRNAs by influencing miRNA processing and/or miRNA-mRNA interactions. The purpose of this study was to investigate the association between 2 SNPs commonly found in precursor miRNA and the susceptibility and clinicopathological characteristics of pancreatic cancer. The rs11614913/miR-196a2, rs2910164/miR-146a SNPs were genotyped in 93 patients with pancreatic cancer and in 122 healthy controls. No significant differences in genotype distributions between controls and PC patients were observed. However, rs2910164 GG and rs11614913 CC genotypes and the rs2910164C/rs11614913C and rs2910164G/rs11614913C haplotypes were significantly overrepresented in PC patients with T1 and T2 tumor status than in those with T3 and T4. Our findings suggested that the rs2910164 and rs11614913 SNPs might play a role in pancreatic tumorigenesis, but the molecular mechanism underlying the particular sequence variations in miRNA that can cause aberrant expression remains to be determined.

Association study of genetic variants in miRNAs in patients with inflammatory bowel disease: preliminary results.

BACKGROUND: Aberrant expression and structural alteration of miRNAs are considered to participate in inflammation and cancer development. It has been suggested that common single-nucleotide polymorphisms (SNPs) in miRNAs are associated with susceptibility to several human diseases. METHODS: In the present preliminary study we evaluated the associations of two SNPs (rs2910164 and rs11614913 in miR-146a and miR-196a2, respectively) with the risk of inflammatory bowel disease (IBD) in a Greek population. RESULTS: The rs2910164 and rs11614913 SNPs were genotyped in 242 patients with Crohn's disease (CD), 210 patients with ulcerative colitis (UC) and 300 healthy individuals. No statistically significant differences were found in the genotype or allele distributions of the rs2910164 SNP among UC and control subjects. However, significant differences were found in the genotype or allele distributions of the rs2910164 polymorphism among CD and control subjects (P < 0.0001 and P < 0.0001, respectively). Concerning the rs11614913, no statistically significant differences were found in the genotype or allele distributions among CD and control patients, whereas TT genotype and T allele seem to have a protective role against UC (P = 0.017 and P = 0.007, respectively). The presence of rs2910164 and rs11614913 SNPs did not influence disease phenotype. CONCLUSIONS: Our results demonstrate that the rs2910164 polymorphism has a major role in genetic susceptibility to CD but not to UC, since the rs11614913 polymorphism had a protective role against UC, at least in the population studied here. Independent studies are needed to validate our findings in larger series and in patients of different ethnic origins.

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.

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.