Multimodal Prehabilitation for Patients with Crohn's Disease Scheduled for Major Surgery: A Narrative Review.

Approximately 15-50% of patients with Crohn's disease (CD) will require surgery within ten years following the diagnosis. The management of modifiable risk factors before surgery is essential to reduce postoperative complications and to promote a better postoperative recovery. Preoperative malnutrition reduced functional capacity, sarcopenia, immunosuppressive medications, anemia, and psychological distress are frequently present in CD patients. Multimodal prehabilitation consists of nutritional, functional, medical, and psychological interventions implemented before surgery, aiming at optimizing preoperative status and improve postoperative recovery. Currently, studies evaluating the effect of multimodal prehabilitation on postoperative outcomes specifically in CD are lacking. Some studies have investigated the effect of a single prehabilitation intervention, of which nutritional optimization is the most investigated. The aim of this narrative review is to present the physiologic rationale supporting multimodal surgical prehabilitation in CD patients waiting for surgery, and to describe its main components to facilitate their adoption in the preoperative standard of care.

Pancreatic Neuroendocrine Tumors in MEN1 Patients: Difference in Post-Operative Complications and Tumor Progression between Major and Minimal Pancreatic Surgeries.

Pancreatic neuroendocrine neoplasms (PNENs) affect over 80% of patients with multiple endocrine neoplasia type 1 (MEN1). Surgery is usually the therapy of choice, but the real immediate and long-term therapeutic benefit of a partial extensive pancreatic resection remains controversial. We analyzed, in 43 PNEN MEN1 patients who underwent 19 pancreaticoduodenectomies (PD), 19 distal pancreatectomies (DP), and 5 minimal pancreatectomies, the prevalence of surgery-derived early complications and post-operative pancreatic sequelae, and the PNEN relapse-free survival time after surgery, comparing major (PD+DP) and minimal pancreatic surgeries. No post-operative mortality was observed. Metastatic cancers were found in 12 cases, prevalently from duodenal gastrinoma. Long-term cure of endocrine syndromes, by the 38 major pancreatic resections, was obtained in 78.9% of gastrinomas and 92.9% of insulinomas. In only one patient, hepatic metastases, due to gastrinoma, progressed to death. Out of the 38 major surgeries, only one patient was reoperated for the growth of a new PNEN in the remnant pancreas. No functioning PNEN persistence was reported in the five minimal pancreatic surgeries, PNEN relapse occurred in 60% of patients, and 40% of cases needed further pancreatic resection for tumor recurrence. No significant difference in PNEN relapse-free survival time after surgery was found between major and minimal pancreatic surgeries.

Surgery for Sporadic Primary Hyperparathyroidism: Evolution over the Last Twenty Years in a Monocentric Setting.

The sporadic parathyroid pathology of surgical interest is primarily limited to lesions that are the cause of hormonal hyperfunction (primary hyperparathyroidism). In recent years, parathyroid surgery has evolved significantly, and numerous minimally invasive parathyroidectomy techniques have been developed. In this study, we describe a single-center and well-documented case series of sporadic primary hyperparathyroidism, surgically treated by a single operator in the Endocrine Surgery Unit of the Surgical Clinic of the University of Florence-Careggi University Hospital, recorded and updated in a dedicated database that embraces the entire evolutionary timeframe of parathyroid surgery. From January 2000 to May 2020, 504 patients with a clinical and instrumental diagnosis of hyperparathyroidism were included in the study. The patients were divided into two groups, based on the application of intraoperative parathyroid hormone (ioPTH). The analysis shows that the use of ioPTH with the rapid method could be ineffective in helping surgeons in primary operations, especially when ultrasound and scintiscan are concordant. The advantages obtained by not using intraoperative PTH are not only economic. In fact, our data shows shorter operating and general anesthesia times and hospital stays, having an important impact on patient biological commitment. Furthermore, the significant reduction in operating time makes it possible to almost triple the volume of activity in the same unit of time available, with an undeniable advantage for the reduction of waiting lists. In recent years, minimally invasive approaches have allowed surgeons to reach the best compromise between invasiveness and aesthetic results.

Effects of the learning curve on operative time and lymph node harvesting during robotic gastrectomy.

BACKGROUND: Gastric cancer is the fifth most frequent cancer globally. The introduction of minimally invasive surgery for gastric cancer aimed at reducing post-operative morbidity and hospital length of stay. Although the role of laparoscopic gastrectomy has been established, robotic gastric surgery has only recently gained popularity. The purpose of this study was to evaluate, with a multidimensional analysis, the learning curve of a single surgeon with extensive experience in laparoscopic gastrectomy. METHODS: We prospectively collected data from 104 gastric cancer patients who underwent surgery with a robotic approach from June 2015 to June 2019 by a single surgeon. We performed 21 total gastrectomies (TGs) and 83 subtotal gastrectomies (STGs). A D2 lymphadenectomy was performed in all the patients. Proximal and distal resection margins were tumoour-free in all patients. There were no intraoperative complications, and no conversions occurred. RESULTS: The plateau of the learning curve based on harvesting lymph nodes and operative time was not reached for TG. The learning curve of operative time for STG could be divided into three different phases: an early or learning phase from 1 to 27 cases, an intermediate or proficiency phase from 28 to 48 cases, and a late or mastery phase from 49 to 83 cases. The learning curve for harvesting lymph nodes was achieved after 41 cases in the STG group. CONCLUSION: This study shows that robotic gastrectomy is a complex procedure with a significant multiphasic learning curve. Nevertheless, the robotic learning curve seems to be more rapid than that of conventional laparoscopy. Most importantly, our results suggest that the robotic technique can provide oncological adequacy in terms of lymph node harvesting even in the very first phase of the learning curve.

Impact of Preoperative Immunonutrition on Oxidative Stress and Gut Barrier Function in Surgical Patients with Crohn's Disease.

Several international guidelines recommend a peri-operative immunonutrition (IN) support for patients care in elective colorectal surgery, to reduce postoperative complications, particularly infections. In Crohn's patients, is also used to mitigate the severity of the disease. We performed a pilot study on 16 Crohn's patients undergoing intestinal surgery for active disease, not responsive to pharmacological treatment; half of them received an oral nutritional supplement enriched with immunonutrients (IN patients) for 7 days prior to surgery, in addition to normal food intake. Markers of oxidative stress (Advanced Glycated End-products (AGEs) and Advanced Oxidation Protein Products (AOPPs) were measured both in plasma and tissue samples wherein the Receptor for Advanced Glycation End products (RAGE) and Tight Junction Protein 1 (TJP1) gene expression were also determined. Plasma AGEs were significantly and positively correlated with tissue levels of AGEs (p = 0.0354) and AOPPs (p = 0.0043) while they were negatively correlated with TJP1 expression (p = 0.0159). The expression of RAGE was also negatively correlated with that of TJP1 gene (p = 0.0146). IN patients exhibited significantly lower AGEs plasma levels (p = 0.0321) and a higher mucosal TJP1 expression (p = 0.0182). No patient had postoperative complications and the length of hospital stay was similar in the two groups, but IN patients, showed a significantly shorter time to resume fluid and solid diet. These preliminary data suggest that IN might support patient's recovery by improving intestinal mucosa barrier function through the regulation of AGEs/RAGE signaling.

Crohn's disease recurrence updates: first surgery vs. surgical relapse patients display different profiles of ileal microbiota and systemic microbial-associated inflammatory factors.

Background and aims: Crohn's disease (CD) pathogenesis is still unclear. Remodeling in mucosal microbiota and systemic immunoregulation may represent an important component in tissue injury. Here, we aim to characterize the ileal microbiota in both pathological and healthy settings and to evaluate the correlated systemic microbial-associated inflammatory markers comparing first-time surgery and relapse clinical conditions. Methods: We enrolled 28 CD patients at surgery; we collected inflamed and non-inflamed mucosa tissues and blood samples from each patient. Bacterial wall adherence was observed histologically, while its composition was assessed through amplicon sequencing of the 16S rRNA gene. In addition, we evaluated the systemic microRNA (miRNA) using quantitative real-time PCR amplification and free fatty acids (FFAs) using gas chromatography-mass spectroscopy. Results: The total number of mucosal adherent microbiota was enriched in healthy compared to inflamed mucosa. In contrast, the phylum Tenericutes, the family Ruminococcaceae, and the genera Mesoplasma and Mycoplasma were significantly enriched in the pathological setting. Significant microbiota differences were observed between the relapse and first surgery patients regarding the families Bacillaceae 2 and Brucellaceae and the genera Escherichia/Shigella, Finegoldia, Antrobacter, Gemmatimonas, Moraxella, Anoxibacillus, and Proteus. At the systemic level, we observed a significant downregulation of circulating miR-155 and miR-223, as well as 2-methyl butyric, isobutyric, and hexanoic (caproic) acids in recurrence compared to the first surgery patients. In addition, the level of hexanoic acid seems to act as a predictor of recurrence risk in CD patients (OR 18; 95% confidence interval 1.24-261.81; p = 0.006). Conclusions: We describe a dissimilarity of ileal microbiota composition comparing CD and healthy settings, as well as systemic microbial-associated inflammatory factors between first surgery and surgical relapse. We suggest that patterns of microbiota, associated with healthy ileal tissue, could be involved in triggering CD recurrence. Our findings may provide insight into the dynamics of the gut microbiota-immunity axis in CD surgical recurrence, paving the way for new diagnostics and therapeutics aimed not only at reducing inflammation but also at maintaining a general state of eubiosis in healthy tissue.

Is the age at surgery in Crohn's disease clinically relevant? Differences and peculiarities: a wide single centre experience after long-term follow-up.

PURPOSE: The Montreal classification for Crohn's disease includes "age at diagnosis" as a parameter but few is reported about the age at surgery. The aim of this study is to evaluate the short- and long-term differences in the postoperative surgical outcome and disease behaviour, according to the age at the first surgery. METHODS: Patients consecutively operated for abdominal Crohn's disease during the period 1986-2012 at our centre were systematically analysed according to their age at first surgery. In our retrospective cohort, the age at first surgery ranged from 13 to 83 years, and patients were arbitrarily divided into four groups: ≤ 19 (G1), 20-39 (G2), 40-59 (G3) and ≥ 60 (G4) years old. RESULTS: In total, 1051 patients were included with a median follow-up time of 232 months. The four groups exhibited statistically significant differences in age at diagnosis, smoke habit, time between diagnosis and surgery, disease location and behaviour, history of perianal fistula or abscess, severe malnutrition requiring total parental nutrition before surgery, type of surgery, total length of resected bowel, median duration of hospitalization, incidence of abdominal recurrences and number of surgical recurrences. G1 displays an inverse linear trend with time in the severity of clinical characteristics when compared to G4 groups. On the contrary, the incidence of short-term complications, types of abdominal recurrence and presence of concomitant perianal disease did not vary among groups. In addition, at multivariate analysis, the age at surgery and the disease location were the only independent risk factors for abdominal surgical recurrence. CONCLUSION: Despite first surgery is extremely more frequent between 20 and 59 years, patients from G1 and G4 groups showed clinical differences and peculiarities when compared to the other age groups. The most indolent CD behaviour and occurrence of surgical recurrence was observed in patients having their first abdominal surgery in the elderly, while patients operated before the age of 19 experienced a more aggressive disease course.

Involvement of MIR-126 and MMP9 in the Pathogenesis of Intra-Abdominal Fistulizing Crohn's Disease: A Brief Research Report.

Background: Intra-abdominal fistulas are complications that affect a significant proportion of Crohn's disease patients, often requiring surgery. The aim of the present work was to correlate the occurrence of intestinal fistulization to the clinico-pathological features of these patients and to the plasma levels of MMP9, a gelatinase involved in the pathophysiology of fistula formation, and of miR-126, appearing to modulate MMP9 expression. Methods: In a series of 31 consecutive Crohn's patients admitted to surgery due to therapeutic failure and/or complicated disease, we identified nine cases of abdominal fistulas, mainly entero-enteric fistulas. MMP9 protein was determined in plasma and at the intestinal level using immunometric assays. Circulating miR-126 was also measured in all plasma samples by real-time PCR. Results: Comparing patients with and without intra-abdominal fistulas, we did not observe differences in terms of age, gender, disease location and duration, number of previous surgeries and pre-biologic medications. However, cases with intra-abdominal fistulas had a significantly higher CDAI (p < 0.0001) and a significantly lower circulating miR-126 (p < 0.05). Patients with intra-abdominal fistulas had also a significantly higher amount of circulating MMP9 (p < 0.0001) and this data was correlated with an increased expression of MMP9 protein in the mucosa and with reduced levels of circulating miR-126. Receiver operating characteristic (ROC) analysis pointed out the ability of circulating MMP9 to discriminate patients with and without intra-abdominal fistulas. Conclusions: These data confirm that circulating MMP9 can be used for the identification of cases with intra-abdominal fistulas and suggest that miR-126 may be also involved in the pathogenesis of this complication and that it may be further investigated as a new therapeutic strategy or for monitoring therapeutic response in these patients.

Chronic Systemic Low-Grade Inflammation and Modern Lifestyle: The Dark Role of Gut Microbiota on Related Diseases with a Focus on COVID-19 Pandemic.

Inflammation is a physiological, beneficial, and auto-limiting response of the host to alarming stimuli. Conversely, a chronic systemic low-grade inflammation (CSLGI), known as a long-time persisting condition, causes damage to the organs and host tissues, representing a major risk for chronic diseases. Currently, a high global incidence of chronic inflammatory diseases is observed, often linked to the lifestyle-related changes that occurred in the last decade. The main lifestyle-related factors are proinflammatory diet, psychological stress, tobacco smoking, alcohol abuse, physical inactivity, and indoor living and working with its related consequences such as indoor pollution, artificial light exposure, and low vitamin D production. Recent scientific evidence found that gut microbiota (GM) has a main role in shaping the host's health, particularly as CSLGI mediator. Based on the lastest discoveries regarding the remarkable GM activity, in this manuscript we focus on the elements of actual lifestyle that influence the composition and function of the intestinal microbial community in order to elicit the CSLGI and its correlated pathologies. In this scenario, we provide a broad review of the interplay between modern lifestyle, GM, and CSLGI with a special focus on the COVID symptoms and emerging long-COVID syndrome.

Immunomodulation by probiotics and prebiotics in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent primary malignancy in patients suffering from chronic liver diseases and cirrhosis. Recent attention has been paid to the involvement of the gut-liver axis (GLA) in HCC pathogenesis. This axis results from a bidirectional, anatomical and functional relationship between the gastrointestinal system and the liver. Moreover, the complex network of interactions between the intestinal microbiome and the liver plays a crucial role in modulation of the HCC-tumor microenvironment, contributing to the pathogenesis of HCC by exposing the liver to pathogen-associated molecular patterns, such as bacterial lipopolysaccharides, DNA, peptidoglycans and flagellin. Indeed, the alteration of gut microflora may disturb the intestinal barrier, bringing several toll-like receptor ligands to the liver thus activating the inflammatory response. This review explores the new therapeutic opportunities that may arise from novel insights into the mechanisms by which microbiota immunomodulation, represented by probiotics, and prebiotics, affects HCC through the GLA.

Adherence to mediterranean diet in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Mediterranean diet may be beneficial for inflammatory bowel disease (IBD). The aim of this study was to evaluate the level of adherence to MD in Italian patients with IBD. METHODS: Eighty consecutive outpatients with IBD, 62 with Crohn's Disease (CD) and 18 with Ulcerative Colitis (UC) were included in the study. Demographic and clinical data, previous and current medical history, nutritional status and Quality of Life (QoL) assessed with the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) were assessed. Adherence to MD was studied with the Medi-Lite questionnaire. RESULTS: IBD patients reported a mean Medi-Lite score of 10.4 with no significant differences between CD and UC patients (p = 0.543). Among CD patients, adherence to MD was higher in patients with inactive disease (p < 0.001) than in patients during the active phase, while no significant difference was found regarding disease activity in UC patients. A significant negative correlation of the Medi-Lite score with SIBDQ score (r = -0.2; p = 0.040) was found. MD adherence was lower in CD patients who had undergone ≥2 surgeries, whereas for patients with UC we found no significant differences in MD adherence in relation to pervious surgery. CONCLUSIONS: Adherence to MD in IBD is influenced by disease activity, QoL and patients' surgical history. A greater adherence to MD achieved with nutritional education may help improve quality of life and modulate disease activity.

Relationship between Nutritional Screening Tools and GLIM in Complicated IBD Requiring Surgery.

BACKGROUND: Accurate identification of malnutrition and preoperative nutritional care in Inflammatory Bowel Disease (IBD) surgery is mandatory. There is no validated nutritional screening tool for IBD patients. We developed a novel nutritional screening tool for IBD patients requiring surgery and compared it with other tools. METHODS: we included 62 consecutive patients scheduled for elective surgery. The IBD Nutritional Screening tool (NS-IBD) was developed to screen patients for further comprehensive assessment. NRS-2002, MUST, MST, MIRT, SaskIBD-NR are compared with the new test. All screening tests were subsequently related to new GLIM criteria. RESULTS: according to GLIM criteria, 25 (40%) IBD patients were malnourished (15 CD and 10 UC, 33% vs. 63%, p = 0.036). Stage 1 malnutrition was reported in ten patients, while stage 2 was detected in 15 patients. The comparison of each nutritional risk tool with GLIM criteria showed sensitivity of 0.52, 0.6, 0.6, 0.84, 0.84 and 0.92 for SASKIBD-NR, MUST, MST, NRS-2002, MIRT, and the new NS-IBD, respectively. CONCLUSIONS: in IBD, currently adopted nutritional screening tools are characterized by a low sensitivity when malnutrition diagnosis is performed with recent GLIM criteria. Our proposed tool to detect malnutrition performed the best in detecting patients that may require nutritional assessment and preoperative intervention.

Thyroidectomy for Cancer: The Surgeon and the Parathyroid Glands Sparing.

BACKGROUND: The diagnosis of thyroid cancer is continuously increasing and consequently the amount of thyroidectomy. Notwithstanding the actual surgical skill, postoperative hypoparathyroidism still represents its most frequent complication. The aims of the present study are to analyze the rate of postoperative hypoparathyroidism after thyroidectomy, performed for cancer by a single first operator, without any technological aid, and to compare the data to those obtained adopting the most recent technological adjuncts developed to reduce the postoperative hypoparathyroidism. METHODS: During the period 1997-2020 at the Endocrine Surgery Unit of the Department of Clinical and Experimental Medicine of the University of Florence, 1648 consecutive extracapsular thyroidectomies for cancer (401 with central compartment node dissection) were performed. The percentage of hypoparathyroidism, temporary or permanent, was recorded both in the first period (Group A) and in the second, most recent period (Group B). Total thyroidectomies were compared either with those with central compartment dissection and lobectomies. Minimally invasive procedures (MIT, MIVAT, some transoral) were also compared with conventional. Fisher's exact and Chi-square tests were used for comparison of categorical variables. p < 0.01 was considered statistically significant. Furthermore, a literature research from PubMed® has been performed, considering the most available tools to better identify parathyroid glands during thyroidectomy, in order to reduce the postoperative hypoparathyroidism. We grouped and analyzed them by technological affinity. RESULTS: On the 1648 thyroidectomies enrolled for the study, the histotype was differentiated in 93.93 % of cases, medullary in 4% and poorly differentiated in the remaining 2.06%. Total extracapsular thyroidectomy and lobectomy were performed respectively in 95.45% and 4.55%. We recorded a total of 318 (19.29%) cases of hypocalcemia, with permanent hypoparathyroidism in 11 (0.66%). In regard to the literature, four categories of tools to facilitate the identification of the parathyroids were identified: (a) vital dye; (b) optical devices; (c) autofluorescence of parathyroids; and (d) autofluorescence enhanced by contrast media. Postoperative hypoparathyroidism had a variable range in the different groups. CONCLUSIONS: Our data confirm that the incidence of post-surgical hypoparathyroidism is extremely low in the high volume centers. Its potential reduction adopting technological adjuncts is difficult to estimate, and their cost, together with complexity of application, do not allow immediate routine use. The trend towards increasingly unilateral surgery in thyroid carcinoma, as confirmed by our results in case of lobectomy, is expected to really contribute to a further reduction of postsurgical hypoparathyroidism.

Xanthomatous Inflammatory Infiltrate Involving the Spleen: An Unusual Presentation of Erdheim-Chester Disease and Review of the Literature.

BACKGROUND Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by foamy histiocytes, Touton-like giant cells, and fibrosis, typically affecting the diaphyseal and metaphyseal region of the long bones but that can involve any organ or tissue. ECD is usually associated with the BRAF V600E mutation or with other molecular mutations inserted in the MAPK cascade. CASE REPORT We present the case of a 63-year-old man with a previous history of myocardial infarction who underwent an emergency splenectomy for splenic rupture after an accidental fall. Histological examination of the spleen showed a diffuse xanthogranulomatous proliferation (CD68+, CD163+, S100-, CD1a-) with rare Touton-like giant cells in the red pulp. Based on the histologic findings, a diagnosis of ECD was made. However, skeletal involvement and BRAF V600E mutation were not detected. CONCLUSIONS Cases of non-Langerhans cell histiocytosis that are histologically consistent with ECD in unusual sites have been increasingly described. There is also anecdotal evidence for cases being associated with mutations besides BRAF V600E or with no genetic alteration and no skeletal involvement. Likewise, the spectrum of clinical and molecular features of ECD can be broader than previously considered. Furthermore, there is evidence that various phases of the disease can show different clinical presentations with distinct prognostic impact, according to the mutational spectrum. Recognizing ECD at an early stage allows more effective patient management, and pathologists and clinicians should be aware of the unusual clinical presentations of this rare condition.

Robotic gastric surgery: a monocentric case series and review of the literature.

INTRODUCTION: The technical complexity of D2 lymphadenectomy and esophago-jejunal anastomosis are the main factors that limit the application of laparoscopic surgery in the treatment of gastric cancer. Robotic assisted gastric surgery provides potential technical advantages over conventional laparoscopy but an improvement in clinical outcomes after robotic surgery has not been demonstrated yet. EVIDENCE ACQUISITION: Data from 128 consecutive patients who had undergone robotic gastrectomy for gastric cancer at our center institution from April 2017 to June 2020 where retrospectively reviewed from a prospectively updated database. A narrative review was then carried out on PubMed, Embase and Scopus using the following keywords: "gastric cancer," "robotic surgery," "robotic gastrectomy" and "robotic gastric surgery". EVIDENCE SYNTHESIS: Ninety-eight patients underwent robotic distal gastrectomy and 30 underwent robotic total gastrectomy. The mean value of estimated blood loss was 99.5 ml. No patients required conversion to laparoscopy or open surgery. The median number of retrieved lymph nodes was 42. No tumor involvement of the proximal or distal margin was found in any patient. The median time to first flatus and first oral feeding was on postoperative day 3 and 5, respectively. We registered 6 leakages (4.6%), namely, 1 duodenal stump leakage and 5 anastomotic leakages. No 30-day surgical related mortality was recorded. The median length of hospital stay was 10.5 days (range 4-37). CONCLUSIONS: Published data and our experience suggest that the robotic approach for gastric cancer is safe and feasible with potential advantages over conventional laparoscopy.

Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients.

BACKGROUND: CARD15/NOD2 is the most significant genetic susceptibility in Crohn's disease (CD) even though a relationship between the different polymorphisms and clinical phenotype has not been described yet. The study is aimed at analyzing, in a group of CD patients undergoing surgery, the relationship between CARD15/NOD2 polymorphisms and the clinical CD behavior after a long-term follow-up, in order to identify potential clinical biomarkers of prognosis. METHODS: 191 surgical CD patients were prospectively characterized both for the main single nucleotide polymorphisms of CARD15/NOD2 and for many other environmental risk factors connected with the severe disease form. After a mean follow-up of 7.3 years, the correlations between clinical features and CD natural history were analyzed. RESULTS: CARD15/NOD2 polymorphisms were significantly associated with younger age at diagnosis compared to wild type cases (p < 0.05). Moreover, patients carrying a 3020insC polymorphism presented a larger Δ between diagnosis and surgery (p = 0.0344). Patients carrying an hz881 and a 3020insC exhibited, respectively, a lower rate of responsiveness to azathioprine (p = 0.012), but no difference was found in biologic therapy. Finally, the risk of surgical recurrence was significantly associated, respectively, to age at diagnosis, to familial CD history, to diagnostic delay, to arthritis, and to the presence of perioperative complications. CONCLUSIONS: 3020insC CARD15 polymorphism is associated with an earlier CD onset, and age at CD diagnosis < 27 years was confirmed to have a detrimental effect on its clinical course. In addition, the familiarity seems to be connected with a more aggressive postoperative course. Finally, for the first time, we have observed a lower rate of responsiveness to azathioprine in patients carrying an hz881 and a 3020insC.

Diving into Inflammation: A Pilot Study Exploring the Dynamics of the Immune-Microbiota Axis in Ileal Tissue Layers of Patients with Crohn's Disease.

BACKGROUND AND AIMS: The pathogenesis of Crohn's disease [CD] is still unclear. Disorders in the mucosal immunoregulation and its crosstalk with the microbiota may represent an important component in tissue injury. We aimed to characterize the molecular immune response distribution within the ileal layers and to evaluate the correlated microbiota in pathological/healthy settings comparing first surgery/relapse clinical conditions. METHODS: We enrolled 12 CD patients. A comprehensive analysis of an ileal mucosa, submucosa and serosa broad-spectrum cytokine panel was performed through a multiplex approach. In addition, ileal microbiota composition was assessed through next generation sequencing. RESULTS: We observed a distinct profile [of IL1-α, IL-1ß, IL-4, IL-8, ICAM-1, E-Selectin, P-Selectin, IP-10, IL 6 and IL 18] across the CD vs healthy ileal layers; and a different distribution of IFN- γ, P-Selectin, IL-27 and IL-21 in first surgery vs relapse patients. In addition, the phylum Tenericutes, the family Ruminococcaceae, and the genera Mesoplasma and Mycoplasma were significantly enriched in the pathological setting. Significant microbiota differences were observed between relapse and first surgery patients regarding the class Bacteroidia, and the genera Prevotella, Flavobacterium, Tepidimonas and Escherichia/Shigella. Finally, the abundance of the genus Mycoplasma was positively correlated with IL-18. CONCLUSIONS: We describe a dissimilarity of cytokine distribution and microbiota composition within CD and adjacent healthy ileal tissue layers and between first operation and surgical relapse. Our results give potential insight into the dynamics of the gut microbiota-immune axis in CD patients, leading to detection of new biomarkers.

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study.

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD.

Nutritional adequacy in surgical IBD patients.

BACKGROUND & AIMS: Despite little evidence available to date, the dietary intake assessment is considered a useful tool to optimize dietary intervention for the improvement of the nutritional status of IBD patients. The primary aim was to compare the dietary intake of IBD patients scheduled for surgery with the dietary reference values (DRVs) for the Italian population (LARN) and the ESPEN guidelines for clinical nutrition in IBD. The secondary aim was to describe the dietary patterns of patients with CD and UC in relation to the disease-specific and nutritional parameters and to compare these results to a control group in order to evaluate if similar nutritional intakes than in oncologic patients are found in IBD. METHODS: Between January 2019 and March 2020, 62 consecutive IBD patients (46 CD and 16 UC) with age from 18 to 79 years scheduled for surgery were recruited. Patients received a comprehensive nutritional assessment, including food or nutrition-related history, anthropometric and body composition measurements. A group of 61 oncologic patients scheduled for colorectal cancer (CRC) surgery was used as control. RESULTS: IBD patients showed a higher caloric and nutritional intake than CRC group, despite a higher frequency of underweight, and a lower prevalence of overweight and obesity. IBD patients showed an inadequate intake of proteins, n-3 PUFA, fiber, iron, calcium, potassium, magnesium, zinc, vitamin D and vitamin B12 according to ESPEN guidelines for clinical nutrition in IBD and LARN. Oral intake was not influenced by gender, IBD subtype, longer duration of disease and previous surgery. In CD, fistulizing behaviour negatively influenced oral intake. CONCLUSIONS: in IBD patients, the evaluation of macronutrients and micronutrients intake before surgery, can contribute to evaluate and to correct the onset of nutritional deficiencies. Specific dietary recommendations seem required, in order to integrate specific nutritional inadequacies. IBD patients referred to surgery have to be considered at high nutritional risk like oncologic patients are.