Post-operative morbidity in Crohn's disease: what is the impact of patient-, disease- and surgery-related factors?

PURPOSE: Over 50% of patients suffering from Crohn's disease (CD) require surgery in their lifetime. Predictors/risk factors of post-operative morbidity and mortality in CD are poorly investigated. We aimed to assess the risk factors of post-operative morbidity/mortality in CD. METHODS: We performed a retrospective cohort study in which all CD patients operated and followed up at our tertiary Inflammatory Bowel Disease Centre from 2014 to 2019 were enrolled. For each patient, we evaluated patient-dependent, disease-dependent and surgery-dependent variables. All patients underwent small bowel and/or colic resections. RESULTS: Of the 165 operated patients, forty-two (25.5%) developed post-operative complications (major complication rate = 9.8%) including wound infection (12.1%), respiratory complications (4.8%), prolonged ileum (4.2%), anastomotic leak (3.6%), urinary infections (3%), abdominal abscess (2.4%), anastomotic bleeding (3.6%), abdominal bleeding (1.2%) and obstruction (0.6%). Two subjects (1.2%) required re-operation within 30 days, and one died. A surgery duration < 141 min was predictive of a better post-operative outcome (sensitivity 80.9%, specificity 43.1%, PPV 32.7%, NPV 86.9%). The multivariable analysis showed stricturing/fistulizing behaviour (OR 3.7, 95% CI 1.6-6.4, p = 0.02), need for total parenteral nutrition (OR 4.1, 95% CI 2.4-9.2, p = 0.01), pre-operative bowel cleansing (OR 0.6, 95% CI 0.41-0.83, p = 0.01) and surgery duration < 141 min (OR 0.2, 95% CI 0.08-0.7, p = 0.03) as the only risk factors associated with post-operative morbidities. CONCLUSIONS: About 25% of CD patients develop post-operative complications. Several patient-related, disease-related and surgery-related factors should be considered risk factors for post-operative morbidity. The recognition of these factors, as well as a multidisciplinary approach to the pre-operative management of CD, could reduce post-operative complications.

Simplified Histologic Mucosal Healing Scheme (SHMHS) for inflammatory bowel disease: a nationwide multicenter study of performance and applicability.

BACKGROUND: Assessment of mucosal healing is important for the management of patients with inflammatory bowel disease (IBD), but endoscopy can miss microscopic disease areas that may relapse. Histological assessment is informative, but no single scoring system is widely adopted. We previously proposed an eight-item histological scheme for the easy, fast reporting of disease activity in the intestine. The aim of the present study was to evaluate the performance of our Simplified Histologic Mucosal Healing Scheme (SHMHS). METHODS: Between April and May 2021 pathologists and gastroenterologists in Italy were invited to contribute to this multicenter study by providing data on single endoscopic-histological examinations for their IBD patients undergoing treatment. Disease activity was expressed using SHMHS (maximum score, 8) and either Simple Endoscopic Score for Crohn's Disease (categorized into grades 0-3) or Mayo Endoscopic Subscore (range 0-3). RESULTS: Thirty hospitals provided data on 597 patients (291 Crohn's disease; 306 ulcerative colitis). The mean SHMHS score was 2.96 (SD = 2.42) and 66.8% of cases had active disease (score ≥ 2). The mean endoscopic score was 1.23 (SD = 1.05), with 67.8% having active disease (score ≥ 1). Histologic and endoscopic scores correlated (Spearman's ρ = 0.76), and scores for individual SHMHS items associated directly with endoscopic scores (chi-square p < 0.001, all comparisons). Between IBD types, scores for SHMHS items reflected differences in presentation, with cryptitis more common and erosions/ulcerations less common in Crohn's disease, and the distal colon more affected in ulcerative colitis. CONCLUSIONS: SHMHS captures the main histological features of IBD. Routine adoption may simplify pathologist workload while ensuring accurate reporting for clinical decision making.

Confocal laser endomicroscopy in ulcerative colitis: beyond endoscopic assessment of disease activity.

BACKGROUND: The aim of this study was to investigate the role of confocal laser endomicroscopy (CLE) in the assessment of disease activity in ulcerative colitis (UC). METHODS: Consecutive patients with UC referred to our inflammatory bowel disease unit for colonoscopy were enrolled. Patients without UC were used as controls. UC activity was evaluated by white light endoscopy and classified according to the Mayo Ulcerative Colitis Endoscopic Score of Severity. Endoscopic biopsies were also taken for histological assessment of disease activity and then assessed with CLE. Three parameters were evaluated; crypt architecture (crypt diameter, inter-crypt distance, presence of fused crypts, crypts regularity), microvascular pattern (regular, dilated, irregular and deformed), fluorescein leakage. RESULTS: Fifty patients with UC and 10 controls were enrolled. At colonoscopy, 11 patients (22%), 19 patients (38%), 12 patients (24%) and 8 patients (16%) presented a Mayo score of 0, 1, 2 and 3, respectively. At CLE, fused crypts were present in all the patients with UC and absent in controls. Crypt diameter and inter-crypt distance showed a parallel increase with the Mayo score. Fluorescein leakage and irregular vessels were more frequently found in case of a high level of endoscopic severity, but were also identified in about 20% of UC patients with normal mucosa. Biopsies also demonstrated the presence of histological activity in 4 patients with endoscopically inactive colitis. CONCLUSIONS: CLE might be a useful tool to determine inflammatory activity in UC. Fused crypts appeared to be a CLE marker of UC, while other abnormalities, like microvascular alteration and fluorescein leakage, have also been identified in patients with mucosal healing at endoscopy. Larger series are required to validate these results and the advantages of a CLE-based assessment of UC activity.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Ultrasonographic diagnosis of ileo-ileal intussusception secondary to Vanek's tumor.

Intussusception is a common condition of bowel obstruction in pediatric patients. However, 5% of all cases occur in adults, mostly aged over fifty, with no difference based on sex, representing about 1% of all causes of bowel obstruction. Compared to pediatric population, it is triggered by a pathologic lead point in about 85% of cases, represented in 60% of cases by malignant and benign neoplasms. Among these neoplasms, an inflammatory fibroid polyp (IFP), a benign neoplastic submucosal lesion also known as Vanek's tumor, is considered a very uncommon cause of adult intussusception. Clinical presentation could differ by location and size of tumor, and may include abdominal pain, nausea, vomiting, diarrhea or constipation, bleeding, weight loss, palpable abdominal mass, bowel obstruction, and gastrointestinal bleeding. Considering its common and non-specific symptoms, radiologic imaging plays a key role in the diagnosis of an IFP, especially computed tomography (CT) scan, which represents the most sensitive modality to confirm intussusception. However, bowel sonography (BS) has become an accurate procedure in various pathological intestinal diseases, also including intussusception. In this paper, we report a rare case of ileo-ileal intussusception secondary to Vanek's tumor diagnosed by BS.

Crohn's disease and Takayasu's arteritis: are they associated?

OBJECTIVE: Different types of vasculitis can occur in patients with inflammatory bowel disease [IBD], but large vessels vasculitis seems to be the most prevalent. Indeed, the presence of both Crohn's disease [CD] and Takayasu's arteritis [TAK] has previously been reported, with higher prevalence in young women between the second and the third decade of life. This article aims to provide clinicians with an accurate picture of the most common clinical features and current treatment strategy for patients with both CD and TAK. PATIENTS AND METHODS: We described the coexistence of CD and TAK in three young women and also performed an extensive literature review about the association of these two immune-related disorders. Research on PubMed server was performed typing the terms "Takayasu's arteritis and inflammatory bowel disease", "Takayasu's arteritis and Crohn's disease", and "Takayasu's arteritis and Ulcerative colitis". RESULTS: Although the association of CD with TAK is uncommon, due to the severity of both diseases, concomitance in the same patient may significantly complicate the diagnostic and therapeutic work-up. In addition, since TAK can compromise intestinal vasculature, it may possibly exacerbate the clinical course of patients with IBD. All patients we reported underwent surgery due to IBD complications and two of them started biological therapy with different outcomes. CONCLUSIONS: Early detention of these conditions has a great importance for both gastroenterologists and immunologists, for ensuring a tailored multidisciplinary management, possibly in order to identify a common therapy for these two immune-related disorders.

Azathioprine for prevention of clinical recurrence in Crohn's disease patients with severe endoscopic recurrence: an IG-IBD randomized double-blind trial.

OBJECTIVE: The recurrence of Crohn's Disease after ileo-colonic resection is a crucial issue. Severe endoscopic lesions increase the risk of developing early symptoms. Prevention and treatment of post-operative Endoscopic Recurrence (ER) have been studied with conflicting results. We compare effi cacy of azathioprine (AZA) vs. high-dose 5-aminosalicylic acid (5-ASA) in preventing clinical recurrence and treating severe post-operative ER. PATIENTS AND METHODS: We performed a 1-year multicenter randomized double-blind double-dummy trial. Primary end-points were endoscopic improvement and therapeutic failure (clinical recurrence or drug discontinuation due to lack of efficacy or adverse events) 12 months after randomization. We also performed a post-trial analysis on symptomatic and endoscopic outcomes 10 years after the beginning of the trial, with a median follow-up of 60 months. RESULTS: Therapeutic failure occurred in 8 patients (17.4%) within 12 months from randomization, with no significant difference between patients treated with 5-ASA (20.8%, 5 patients) and those with AZA (13.6%, 3 patients). Therapeutic failure was due to clinical recurrence in the 5-ASA group and to adverse events in the AZA group. Endoscopic improvement at 12 months was observed in 8 patients, 2 (11.8%) in the 5-ASA group and 6 (30%) in the AZA group. No serious adverse event was recorded. At the post-trial analysis (median follow-up 60 months), 47.8% (22/46) of patients experienced clinical recurrence: 54.2% (13/24) in the 5-ASA group and 40.9% (9/22) in the AZA group, p=0.546. Patients treated with AZA had lower risk of drug escalation. Clinical recurrence was associated with smoking (p=0.031) and previous surgery (p=0.003). CONCLUSIONS: Our trial indicates that there was no difference in terms of treatment failure between 5-ASA and AZA in patients with severe ER. The main limit of AZA is its less favorable safety profile.

Systematic review with meta-analysis: impact of one-handed vs. two-handed technique on quality outcomes of colonoscopy.

OBJECTIVE: Colonoscopy is usually performed with the one-handed technique (1HT), although several countries and operators still adopt the two-handed technique (2HT). It is still uncertain whether the 1HT can improve the quality outcomes of colonoscopy. We performed a systematic review with meta-analysis to explore the quality outcomes in patients undergoing 1HT or 2HT colonoscopy. MATERIALS AND METHODS: We performed a systematic review with meta-analysis to compare the pooled rates of adenoma detection rate (ADR), cecal intubation rate (CIR), cecal intubation time (CIT), and withdrawal time (WT), in patients undergoing 1HT or 2HT colonoscopy via PubMed/EMBASE, SCOPUS, and Cochrane databases. The primary outcome was the pooled rate of ADR and CIR. CIT and WT were also assessed. Pooled odds ratio (OR), standard mean differences (SMD), and 95% confidence intervals (CI) were calculated using fixed or random-effect models. RESULTS: Five studies (15,763 patients) met the inclusion criteria. The pooled ADR was not significantly different between the two techniques (OR 1.10; 95% CI 0.88-1.39; p=0.16), and CIR was not significantly different in 1HT from 2HT (OR 0.757; 95% CI 0.55-1.02; p=0.07), with no significant heterogeneity. Furthermore, no significant differences were seen for CIT (SMD 0.95; p=0.62) and WT (SMD 0.58; p=0.74). CONCLUSIONS: The 1HT colonoscopy does not add relevant improvement in the quality and efficacy of colonoscopy.

L-Carnitine in the treatment of fatigue in adult celiac disease patients: a pilot study.

BACKGROUND: Fatigue is common in celiac disease. L-Carnitine blood levels are low in untreated celiac disease. L-Carnitine therapy was shown to improve muscular fatigue in several diseases. AIM: To evaluate the effect of L-carnitine treatment in fatigue in adult celiac patients. METHODS: Randomised double-blind versus placebo parallel study. Thirty celiac disease patients received 2 g daily, 180 days (L-carnitine group) and 30 were assigned to the placebo group (P group). The patients underwent clinical investigation and questionnaires (Scott-Huskisson Visual Analogue Scale for Asthenia, Verbal Scale for Asthenia, Zung Depression Scale, SF-36 Health Status Survey, EuroQoL). OCTN2 levels, the specific carnitine transporter, were detected in intestinal tissue. RESULTS: Fatigue measured by Scott-Huskisson Visual Analogue Scale for Asthenia was significantly reduced in the L-carnitine group compared with the placebo group (p=0.0021). OCTN2 was decreased in celiac patients when compared to normal subjects (-134.67% in jejunum), and increased after diet in both celiac disease treatments. The other scales used did not show any significant difference between the two celiac disease treatment groups. CONCLUSION: L-Carnitine therapy is safe and effective in ameliorating fatigue in celiac disease. Since L-carnitine is involved in muscle energy production its decreased absorption due to OCTN2 reduction might explain muscular symptoms in celiac disease patients. The diet-induced OCTN2 increase, improving carnitine absorption, might explain the L-carnitine treatment efficacy.

Endoscopic management of symptomatic choledocholithiasis in pregnancy without the use of radiations.

We report a case of 26-year-old woman at 10th week of gestation with cholestatic jaundice due to a common bile duct (CBD) stone managed by endoscopical retrograde cholangiopancreatography (ERCP). The procedure was successfully carried out without the use of ionizing radiations and under trans-abdominal ultrasonographical (US) control. A few cases are reported in literature in which ERCP was performed without fluoroscopy examination. We believe that ERCP with US guidance is an effective and safe procedure to treat symptomatic choledocholithiasis in pregnant women.

Increased risk of breast cancer in first-degree relatives of Crohn's disease patients. An IG-IBD study.

BACKGROUND: Increased rates of colorectal cancer have been reported in patients with ulcerative colitis as well as with Crohn's colitis. This risk could be the result of shared genetic susceptibility and could be co-inherited rather than being just secondary to a long-standing, extensive mucosal inflammation. AIM: To assess the prevalence of all malignancies in first-degree relatives of Crohn's disease patients in order to establish whether any association exists. PATIENTS AND METHODS: A total of 632 outpatients with a diagnosis of Crohn's disease and 632 control subjects were recruited. Information concerning the presence of malignancies was collected in 3,292 first-degree relatives of Crohn's disease patients and in 3,303 first-degree relatives of controls. RESULTS: Two hundred and fourteen (6.5%) subjects were found to be affected by malignancy in the first-degree relatives of Crohn's disease patients and 180 (5.5%) in the first-degree relatives of controls. Forty-seven (7.4%) of Crohn's disease patients had a first-degree relative with IBD, but none of them had cancer. The frequency of extra-intestinal malignancies was higher in first-degree relatives of Crohn's disease patients than in those of controls (p=0.011). Frequency of breast cancer in female relatives of Crohn's disease patients, mainly in mothers, was two-fold higher than that in controls (0.91% versus 0.42%; odds ratio=2.16; 95% confidence interval=1.14-4.08; p=0.015). The presence of breast cancer showed no association with any specific phenotype of disease in Crohn's patients. CONCLUSIONS: These results did not corroborate the hypothesis about a common genetic susceptibility between Crohn's disease and colorectal cancer. An unexpected finding was the more frequent occurrence of extra-digestive malignancies. The prevalence of breast cancer in first-degree relatives of Crohn's disease patients, in particular the mothers, was more than double than in those of controls. This association, if confirmed, would suggest that there may exist common genetic and/or environmental factors for Crohn's disease and breast cancer.

The role of calprotectin in predicting endoscopic post-surgical recurrence in asymptomatic Crohn's disease: a comparison with ultrasound.

BACKGROUND AND OBJECTIVES: Faecal calprotectin is predictive of clinical relapse in inflammatory bowel disease and ultrasound is sensitive in detecting its post-surgical recurrence. However, no data regarding the role of calprotectin in predicting post-surgical recurrence in asymptomatic Crohn's disease are available. The aim of this study was to prospectively evaluate the role of calprotectin as a predictive marker for one year post-surgical endoscopic recurrence in comparison with ultrasound in patients with asymptomatic Crohn's disease. MATERIAL AND METHODS: We consecutively enlisted 50 patients who had undergone a resection for Crohn's disease. Faecal calprotectin was analysed and ultrasound were performed at the third month, and a colonoscopy after one year. The sensitivity and specificity of these two techniques were evaluated using endoscopic findings as a golden standard. A Receiver Operator Curve (ROC) curve was plotted, in order to identify the best-cut off value for calprotectin. RESULTS: 39 out of 50 patients were evaluated by performing a colonoscopy after one year; 19 patients had an endoscopic recurrence after one year. Calprotectin sensitivity and specificity were calculated for 5 different cut-off values; the best cut-off value for calprotectin sensitivity (63%) and specificity (75%) was > 200 mg/L. The US sensitivity and specificity at the third month were 26% and 90% respectively. CONCLUSIONS: When performed three months after surgery ultrasound is more specific than calprotectin in predicting endoscopic recurrence. Faecal calprotectin at a dosage > 200 mg/L seems to have a better sensitivity than ultrasound. Values of calprotectin > 200 mg can be an indication to colonoscopy in the group of patients with negative ultrasound in order to detect early recurrence.

Infliximab in the treatment of Crohn's disease: predictors of response in an Italian multicentric open study.

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.

Source segregation and food waste prevention activities in high-density households in a deprived urban area.

A waste audit and a household questionnaire survey were conducted in high-density housing estates in one of the most economically and socially deprived areas of England (Haringey, London). Such areas are under-represented in published research. The study examined source segregation, potential participation in a food waste segregation scheme, and food waste prevention activities in five estates (1034 households). The results showed that: contamination of recyclables containers was low; ca. 28% of the mixed residual waste's weight was recyclable; food waste comprised a small proportion of the waste from these residents, probably because of their relatively disadvantaged economic circumstances; and the recycling profile reflected an intermittent pattern of behaviour. Although the majority of respondents reported that they would participate in a food waste separation scheme, the response rate was low and many responses of "don't know" were recorded. Municipalities committed to foster improved diversion from landfill need to recognise that there is no "quick and easy fix", regardless of local or national aspirations. Lasting and sustained behaviour change requires time and the quality of service provision and associated infrastructure play a fundamental role in facilitating residents to participate effectively in waste management activities that maximise capture of source-segregated materials. Populations in deprived areas that reside in high-rise, high-density dwellings are "hard-to-reach" in terms of participation in recycling schemes and exceptional efforts and additional resources are usually required to improve performance.

Protein-loosing enteropathy in sclerosing mesenteritis.

Sclerosing mesenteritis (SM) is a rare, idiopathic disorder of unknown aetiology that involves the adipose tissue of the mesentery, being characterized by chronic and non-specific fibrous inflammation. Patients usually present with non-specific clinical manifestations, such as abdominal pain and diarrhoea. The diagnosis of SM is difficult and it can be definitely established only by means of surgical or imaging-guided biopsy. Different therapeutic strategies have been used in case series with different rate of success. The disease is generally self-limiting, and the long-term prognosis is good, even if some cases of severe SM are reported in literature. Here, we report a fatal case of sclerosing mesenteritis associated to protein-losing enteropathy.