Long-standing Crohn's Disease Research Articles

Occult small bowel adenocarcinoma in Crohn's disease-more than a simple stricture

Small-bowel adenocarcinoma (SBA) accounts for less than 5% of all gastrointestinal cancers. It is generally linked to genetic disorders and immune-mediated inflammatory conditions like Crohn's disease (CD). Despite advances in oncology, SBA has a poor prognosis and high relative risk in this subgroup of patients. Risk factors for the development of SBA in patients with CD include a stricture phenotype and a long- standing disease. This article aims to expose a case of association between CD and SBA and its management. A 66-year-old woman with long-standing terminally ileum-affected CD with multiple admissions due to sub-occlusive episodes and weight loss. CT and MRI revealed intestinal thickening in the small bowel, suggesting an inflammatory stenosis and entero-enteric fistulous tracts. An ileocolectomy was performed, and the patient's histopathological evaluation revealed a mucinous invasive adenocarcinoma of the terminal ileum. The patient was treated with adjuvant chemotherapy and has been under surveillance for two years, without malignant recurrence. Although it is a relatively rare neoplasm, CD patients have a significant risk of developing SBA, when compared to the general population. Diagnosis is challenging due to the occult nature of CD-associated SBA, and imaging and endoscopy alone make it difficult to detect the pathology. Treatment involves a high index of suspicion for the diagnosis and a balance between extended mesenteric resection and CD surgery's primary idea of bowel length preservation. Despite recent advances in oncology, the survival rate in CD-SBA patients remains low. Long-standing CD patients should have the terminal ileum monitored regularly and surgeons should be aware for occult SBA. Post-resection patient surveillance involves regular abdominal exams, serial surveillance, cross-sectional imaging, and monitoring for obstructive symptom recurrence. There is a lack of clear guidelines for primary prevention and surveillance of SBA, with a focus on inflammation management. Preoperative diagnosis techniques are scarce, and patients risk suboptimal treatment if incidental cancer is found. Strategies include right mesenteric-based surgical techniques and/or frozen section exam, always balancing cancer treatment and bowel preservation which is of high relevance in this subgroup of patients.

DOP04 Screening and management of fistula cancers in patients with perianal fistulising Crohn’s Disease: an expert consensus

Abstract Background Fistula cancer is a rare and often devastating diagnosis in patients with perianal fistulising Crohn’s disease (CD). Fistula cancer management is a complex process requiring multi-disciplinary effort. However, given the low incidence and subsequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of fistula cancer. To inform clinical practice, we developed consensus guidelines on fistula cancer in perianal fistulising Crohn’s disease by multidisciplinary experts from the international TOpCLASS consortium. Methods We performed a systematic review of the literature by standard methodology, using the Newcastle-Ottawa quality assessment tool. Data were retrieved from articles according to these domains: epidemiology and risk factors, clinical presentation, diagnostics, staging, and treatment. We developed consensus statements using a Delphi consensus approach. Participants included gastroenterologists, surgeons, radiologists, and pathologists. We performed two rounds of voting: (1) online survey followed by statement edits and (2) hybrid meeting with discussion until over 80% consensus was achieved for each statement. Results Of 550 articles identified, 99 were eligible, and 80 articles were included. The overall quality of evidence was low. Seven statements were accepted in the final consensus (Table 1). Patients with longstanding (>10 years) perianal fistulising CD should be considered at small but increased risk of developing fistula cancer, including anal squamous cell cancer (SCC) and anorectal carcinoma. Risk factors for anal SCC, including human papilloma virus (HPV), should be considered. Clinical signs and symptoms of fistula cancers are non-specific, and several case reports included asymptomatic patients. New or refractory/progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Regarding diagnostics, multiple modalities may be required, including repeated exam under anesthesia with biopsy. Multidisciplinary team efforts were deemed central for the management of fistula cancers. Conclusion Clinicians managing patients with perianal fistulising CD should be aware of the risk of fistula cancers, including anal SCC and anorectal carcinoma. Our expert consensus recommends consideration of patient factors including duration of fistulas, HPV status, and perianal symptoms, and gives guidance on diagnostic modalities and treatment considerations. Multidisciplinary coordination of care is paramount, and more studies in the field are needed.

Disproportionately Low Albumin and High Neutrophil-to-Lymphocyte Ratio in Small Bowel Adenocarcinoma Patients With Long-Duration Crohn's Disease.

Although Crohn's disease (CD) is a known risk factor of small bowel adenocarcinoma (SBA), early diagnosis remains a significant clinical challenge. Identification of biomarkers for SBA may lead to early detection. This is a retrospective study comparing albumin levels and neutrophil-to-lymphocyte ratio (NLR) of patients with long-standing CD who underwent small bowel resection with and without malignancy. Forty-two patients with CD were included in this study (11 with SBA). Median NLR before surgery was 8.5 (interquartile range 6.2-31.3) in patients with SBA and 3.8 (interquartile range 2.8-5.3) for patients without SBA ( P < 0.05). Mean albumin levels before surgery were significantly lower among patients with SBA compared with patients without SBA (2.6 ± 0.6 g/dL vs 3.5 ± 0.6 g/dL, respectively, P < 0.05), despite patients with SBA being under longer total parenteral nutrition treatment duration. CD patients with SBA diagnosis have increased NLR and lower albumin before surgery compared with CD patients without detection of SBA.

Gemella morbillorum as the Culprit Organism of Post-Colonoscopy Necrotizing Perineal Soft Tissue Infection in a Diabetic Patient With Crohn’s Disease

Gemellsa morbillorum (G. morbillorum) is a Gram-positive facultative anaerobe and a known commensal organism of the oropharyngeal and gastrointestinal tracts. It is considered a rare cause of infections in humans. Most of the documented infections, whereas G. morbillorum has been implicated as a causative pathogen, were infective endocarditis and deep visceral abscesses. However, there are only a handful of cases in the current literature that have reported G. morbillorum as the primary organism causing necrotizing soft tissue infections. The authors presented a rare case of post-colonoscopy necrotizing perineal soft tissue infections in an elderly patient with poorly controlled diabetes mellitus and Crohn’s disease with G. morbillorum being the culprit pathogen of this necrotizing infection. The reported case raises concerns for this commensal organism as an emerging virulent pathogen in certain high-risk patients. The authors proposed that a combination of the long-standing Crohn’s disease and the recent colonoscopy with rectal polypectomy has predisposed the patient to G. morbillorum bacteremia with perineal sepsis in the setting of diabetic immunosuppression. Further studies are warranted to ascertain whether G. morbillorum is acquiring increased virulence that would have enabled this organism to cause novel soft tissue infections.

P209 Disproportionate low albumin and high neutrophil-to-lymphocyte ratio in small bowel adenocarcinoma in long-term Crohn’s disease patients

Abstract Background Although Crohn’s disease (CD) is a known risk factor for small bowel adenocarcinoma (SBA), early diagnosis remains a significant clinical challenge with many cases diagnosed inadvertently during small bowel resection or biopsies performed for presumed active or structuring CD. Identification of biomarkers for SBA may lead to early detection and improved prognosis in CD patients. The aim of the study was to explore a possible association between two simple laboratory values – serum albumin levels and neutrophil-to-lymphocyte ratio (NLR) and SBA in CD patients. Methods A retrospective case-control study comparing long-standing (&amp;gt;10 years) CD patients who have undergone small bowel (SB) resection with carcinoma detection by histopathology examination, compared with long-standing CD patients who underwent SB resection without malignancy detection at a ratio of 1:3 of cases to controls. Demographics, disease behavior, NLR, albumin levels and total parenteral nutrition (TPN) status during the three months period prior to surgery were retrieved and compared between groups. Results Forty-two patients with long-standing CD were included (11 with SBA and 31 patients without SBA). Median age was 55 [Interquartile range (IQR) 44–65] in the malignancy group and 37 (IQR 31–47) in the no-malignancy group (p-value &amp;lt; 0.05). Median NLR in the three months prior to surgery was 8.5 (IQR 6.2–31.3) in SBA patients and 3.8 (IQR 2.8–5.3) for patients without SBA (p &amp;lt; 0.05). Mean albumin levels during the three months period prior to surgery were significantly lower among patients with SBA compared with patients without SBA (2.6 ± 0.6 g/dL versus 3.5 ± 0.6 g/dL, respectively, p &amp;lt; 0.05), despite SBA patients being treated with TPN for significantly longer duration. Conclusion CD patients with SBA have statistically significant increased NLR and lower albumin compared with surgically treated CD patients without SBA. If corroborated by further studies, high NLR and disproportionate low albumin levels in long-duration CD patients may be useful biomarkers of SBA.

Removal of Large Urinary Stone Using Percutaneous Nephrolithotomy in a Patient with Crohn’s Disease

&lt;p&gt;Extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD) is approximately 36%. Of genitourinary complications as an EIM of Crohn’s disease (CD), nephrolithiasis is the most common urinary complication in patients with CD. CD patients have been shown to have decreased urinary volume, pH, magnesium, and excretion of citrate, all of which are significant risk factors for nephrolithiasis. Genitourinary complications often occur in case of a severe longstanding disease and are associated with, the activity of bowel disease, especially in those who have undergone bowel surgery. As uncontrolled nephrolithiasis could impair renal function as well as adversely affect quality of life, proper monitoring, early detection, and prevention of the occurrence of urologic complications in CD is crucial. Few data are available about urolithiasis in patients with CD. Herein we report a case of a successful removal of a 2.7 cm calcium oxalate stone using percutaneous nephrolithotomy from a patient with long-standing CD with a previous surgery for small intestinal and colonic stricture.&lt;/p&gt;

96 Mixed Adenoneuroendocrine Carcinoma in Crohn's Disease: A Case Report and Literature Review

Abstract Introduction Mixed adenoneuroendocrine carcinoma (MANEC) is a rare neoplasm with dual adenocarcinomatous and neuroendocrine differentiation. Subgroup analysis demonstrates an increased frequency of both adenocarcinomas and neuroendocrine tumours in patients with Crohn’s disease (CD), though the incidence of MANEC is unknown. Method A 58-year-old male with a 31-year history of CD presented with small bowel obstruction. After failed conservative management, the patient underwent right hemicolectomy, with subsequent histology demonstrating MANEC. A literature search was performed to identify further cases of patients with concomitant MANEC and CD. Results 11 cases were identified. The mean duration of CD before presentation was 19.5 years, and 58% of cases involved the terminal ileum. 60% of cases demonstrated nodal spread and metastatic disease was evident in 25%. 42% of patients with MANEC were initially treated for an exacerbation of CD. Conclusions MANEC is a rare tumour of uncertain aetiology. The terminal ileum is commonly affected, with most cases exhibiting a longstanding CD history. Diagnosis is challenging, with symptoms of MANEC mirroring exacerbations of CD. Future research should strive to identify imaging modalities or biochemical markers which aid in distinguishing the two pathologies, preventing futile medical management of MANEC, and reducing the risk of metastatic spread due to delayed diagnosis.

Small bowel adenocarcinoma arising in longstanding fibrostenotic Crohn’s disease

Empirical evidence suggesting a link between neoplasia and chronic inflammation was first noted by Virchow more than a century ago, but the intricacies of the involved pathological processes have not yet been entirely elucidated. With a growing number of Crohn’s disease (CD) cases worldwide, it is only logical to consider that the complications of this entity would become proportionally more prevalent. We report a case of small bowel adenocarcinoma arising in a patient with longstanding CD and discuss the current differences in paradigms related to surgical decisions in patients with inflammatory small bowel disease. A 56-years-old male patient known with CD was admitted in emergency to our clinic for intense diffuse abdominal pain spontaneously and on palpation, Blumberg +, with signs of peritoneal irritation, episode apparently much more severe compared to the previous ones. Laboratory investigations confirmed the diagnosis of acute abdomen and immediate surgery was performed. Intraoperative findings were peritonitis due to ileal perforation and ileal adenocarcinoma with “signet ring” cells, moderately differentiated (G2), on the background of active inflammatory bowel disease (CD). Segmental enterectomy and ileostomy were performed. The postoperative outcome was relatively favorable, with resumption of digestive tolerance and of intestinal transit at ileostomy level. As increased evidence suggest causality between chronic inflammation and malignant transformation one should contemplate whether the old treatment paradigms applied for other conditions such as fistulae in anal and leg ulcers should not be translated to inflammatory bowel disease (IBD) patients. Are we doing too much or not enough surgery for IBD? Could we diagnose small bowel adenocarcinomas in CD in early stages or there is too much risk for the patients and very few to benefit from a more aggressive surveillance?

Early Combined Immunosuppression Reduces Complications in Long-standing Crohn's Disease: A Post Hoc Analysis of REACT

Crohn's disease (CD) can lead to bowel damage, stricturing, and obstruction thereby resulting in surgery and hospitalization. The Randomized Evaluation of an Algorithm for Crohn's Treatment (REACT) trial showed that early combined immunosuppression (ECI) with symptom-based treatment escalation for 24 months resulted in a lower risk of surgery, hospitalization, or CD-related complications compared with conventional management (CM).1 Treatment earlier in the disease course may be associated with reduced risk of complications compared with later initiation, although data are sparse.2 We performed a post hoc analysis of REACT to evaluate the impact of baseline disease duration on surgery, hospitalization, or CD-related complications in patients treated with ECI compared with CM.

DOP26 Real-life dosing patterns and concomitant drug use among ustekinumab-treated patients with Crohn’s disease

Abstract Background Real-life long-term evidence on ustekinumab treatment in patients with Crohn’s disease (CD) is limited. We performed a retrospective non-interventional nation-wide chart review study of dosing and long-term clinical outcomes in Finnish CD patients treated with ustekinumab (FINUSTE2, EUPAS30920). Methods FINUSTE2 was carried out in 17 Finnish centres. Eligible patients were adults with CD, receiving an intravenous (IV) first dose of ustekinumab during 2017 or 2018. Data on disease activity, dosage, and concomitant medications were collected at baseline, 16 weeks, and 1 year from treatment initiation. All measurements on ustekinumab trough concentrations (TC) were recorded. Results The study included 155 patients (48% female) with a mean age of 44 and disease duration of 14 years. The disease was stricturing or penetrating in 69% of patients, 59% had prior CD-related surgeries, and 96% had a treatment history of at least one biologic agent. After one IV dose and one to two subcutaneous (SC) doses at 8 to 16 weeks, 140 patients (93%) continued to maintenance treatment with SC ustekinumab, of which nearly three-quarters with a dosage interval of 8 weeks (Figure 1). Of 93 patients with a follow-up of at least 1 year, 77 were still on ustekinumab. During follow-up, 55 patients (39%) had their ustekinumab dose adjusted, mostly (n = 44, 31.4%) as a shortening of the dosage interval. Forty-nine patients had in total 65 ustekinumab TC measurements performed, with a mean of 2.2 µg/ml at 16 weeks (n = 23) and 2.7 µg/ml at 1 year (n = 25). In 67% of cases, the reason for measuring TC was lack of or insufficient response. No anti-drug antibodies appeared at any time point. The proportion of patients on ustekinumab monotherapy increased significantly, from 34% (n = 52) at baseline to 54% (n = 79/146; p &amp;lt; 0.001) at 16 weeks and 64% (n = 49/77; p &amp;lt; 0.01) at 1 year. Correspondingly, corticosteroid use decreased significantly, and a trend towards reduced use of immunomodulators was observed (Figure 2). Conclusion In this nationwide real-life study, treatment with ustekinumab in patients with longstanding and complicated CD was persistent and allowed for significant corticosteroid tapering. A vast majority started the maintenance treatment with an 8-week dosage interval and nearly one-third of all patients required a dose increase, suggesting a highly refractory disease phenotype. The lack of detected antidrug antibodies during follow-up indicates low immunogenicity for ustekinumab.

P499 Objectively assessed disease activity during ustekinumab treatment in a nationwide real-life Crohn’s disease cohort

Abstract Background Real-life long-term evidence on ustekinumab treatment response in patients with Crohn’s disease (CD) is scarce. We performed a retrospective non-interventional nationwide chart review study of dosing and long-term clinical outcomes in Finnish CD patients treated with ustekinumab (FINUSTE2, EUPAS30920). Methods FINUSTE2 involved 17 Finnish centres. Eligible patients were adults with CD, receiving an intravenous first dose of ustekinumab during 2017 or 2018. Disease activity data, such as C-reactive protein (CRP), faecal calprotectin (fCal), and the Simple Endoscopic Score for Crohn’s disease (SES-CD) were collected at baseline, 16 weeks, and one year from treatment initiation. A local gastroenterologist at each centre collected the data from health records in an electronic standardised health questionnaire. Results One hundred and fofty-five patients (48% female) with a mean age of 44 and disease duration of 14 years initiated ustekinumab treatment for CD. Table 1 summarises patient characteristics at baseline. After induction consisting of one intravenous dose and one to two subcutaneous doses at 8 to 16 weeks, 140 patients (93%) continued to maintenance treatment with subcutaneous ustekinumab. Of 93 patients with a follow-up of at least one year, 77 were still on ustekinumab. During ustekinumab treatment, SES-CD (10 at baseline, 3 at 1 year, medians, p = 0.033) and CRP (7 mg/l at baseline, 5 mg/l at 1 year, medians, p &amp;lt; 0.001) and fCal (776 μg/g at baseline, 305 μg/g at 1 year, medians, p &amp;lt; 0.001) decreased significantly in those patients with data available. Figure 1 describes changes in fCal levels over time. Conclusion In this nationwide real-life long-term follow-up study, covering all major centres in Finland, ustekinumab treatment of patients with highly refractory and long-standing CD effectively reduced inflammatory activity, assessed by endoscopy, CRP, and fCal.

102P - Clinical features of anorectal cancer in patients with Crohn’s disease: Japanese single center study

BackgroundPatients with long-standing Crohn’s disease (CD) are at a high risk of development of anorectal cancer (ARC), however, the clinical features of ARC complicating CD are still uncertain. The aim of the present study was to clarify the clinical features of ARC complicating CD. MethodsFrom 1995 to 2018, 483 patients with CD underwent surgery in our hospital. Of the 483 patients, 14 patients (2.9%) were diagnosed with ARC. A detailed review of the medical records of the patients was undertaken. ResultsThe median age at diagnosis of ARC was 45 years (25-72 yrs). The median time interval between the diagnosis of CD and ARC was 21 years (7-40 yrs). Eight patients had fecal diversion because of their perianal disease. Ten patients had cancer-related symptoms. The other 4 patients had no cancer-related symptom, but serum CEA was elevated in the 2 of the 4 patients. The 4 patients were diagnosed by cancer surveillance biopsy and 3 of the 4 patients (75%) underwent R0 resection. On the other hand, only 2 of the 10 patients (20%) underwent R0 resection in patients who had cancer-related symptom at the diagnosis of ARC. The surgical procedures were as follows: abdominoperineal resection (n = 6), total pelvic exenteration (n = 3), total proctocolectomy (n = 1), loop ileostomy (n = 3), and exploratory laparotomy (n = 1). UICC staging was as follows: stage I;2. stageII;3, stageIII;4, stageIV;5. After the surgery, chemoradiotherapy was performed in 4 patients, chemotherapy in 4, and radiotherapy in 1. All the patients who underwent R0 resection achieved 5-year relapse free survival, while the 1-year / 2-year overall survival rate of the patients’ group who underwent R1 and R2 resection was 75%/50% (R1) and 40%/0% (R2), respectively. ConclusionsARC was not rare in the patients with long-standing CD. The prognosis is poor in patients’ group with R1/R2 resection, while, patients’ group who achieved R0 resection is good. There is a pressing need to develop strategies for the early detection of ARC. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

2042 A Therapeutic Misadventure With Helminth Therapy for IBD

INTRODUCTION: Intestinal colonization by helminths has decreased in the developing world coinciding with an increased prevalence of inflammatory bowel disease (IBD) in these regions. This has raised the question of the protective role these parasites play in attenuating intestinal inflammation. Trichuris suis ova (TSO), porcine whipworm, has been evaluated as a possible therapy for IBD, but the most recent meta-analysis of efficacy and safety of this treatment showed no clinically significant benefit in inducing remission. We describe a case of a patient with Crohn’s disease whose symptoms were exacerbated by self-administered helminth therapy. CASE DESCRIPTION/METHODS: A 24-year-old male with a longstanding Crohn's disease presented with active colonic inflammation. Patient learned of a clinical trial involving ingestion of TSO, and failing to qualify, independently obtained T. trichiura, human whipworm, and hookworm products from an online vendor marketing themselves as a safe alternative to standard IBD therapy. Following a protocol under advisement from the vendor, the patient ingested whipworm ova and applied hookworm ova to his arm regularly for six months, in the meantime refusing standard IBD therapy. Failing to improve, the patient was eventually started on infliximab infusions and obtained clinical remission. Stool studies for Ova and Parasites negative prior to starting biologic therapy. Five years later while still on biologic therapy, the patient presented with worsening abdominal pain and diarrhea. Colonoscopy was performed and showed quiescent Crohn's colitis with live helminth seen in the cecum. Stool studies confirmed Trichuris trichiura worm and eggs. Patient was treated with mebendazole 100 mg and clinical remission was restored. Patient has been asymptomatic since parasite treatment and continues to be maintained on infliximab. DISCUSSION: This case illustrates the risk associated with the vast naturopathic products marketed for the treatment of IBD. Patients have an arsenal of products at their disposal, many sold based on loose or inconclusive data, not overseen by federally guided regulatory supervision. Through an internet search, we identified several vendors marketing helminths for the treatment of IBD and other illnesses. The availability of these products needs to be recognized when treating patients with IBD, and the presence of parasites needs to be tested when diagnosing and treating such patients, even those from regions of the world where these infections are uncommon.

P106 Small bowel adenocarcinoma in the setting of Crohn's disease: systematic review of the literature

BACKGROUND: Small bowel cancer (SBC) is a rare entity that can be associated with Crohn's Disease. The incidence of SBC in patients with CD is increased by 18.75-fold compared to normal population. The pathogenesis of SBC in the setting of CD is not fully understood, but the disease has a poor prognosis due to diagnostic challenges associated with the primary disease. The aim of this study is to present 2 cases treated within a year in a high volume IBD center and to conduct a systematic literature review of small bowel adenocarcinoma (SBA) associated with small bowel CD. METHODS: Systematic literature review was done by using MEDLINE and EMBASE databases and data regarding demographics, presentation, diagnosis, treatment and survival were extracted. Articles that did not clearly state the location of the Crohn's disease and type of the cancer were excluded. RESULTS: We identified 216 patients diagnosed with small bowel adenocarcinoma in the setting of small bowel Crohn's disease from 117 studies. In this review obstruction was the most common initial symptom (n = 82, 59%; data are missing in 77 patients). Other common symptoms were abdominal pain (n = 12), anemia-bleeding (n = 11), diarrhea (n = 10), and fistulas (n = 5). there were 206 patients with one adenocarcinoma and 10 patients with 2 different adenocarcinomas. Among the patients with only one tumor, 154 patients (74.7%) were found to have ileal SBA. The median time to diagnosis of SBA from the diagnosis of CD was 18 months (1-300 months, data on 10 patients were missing). Out of 129, 64 patients (49.6%) were diagnosed with cancer after the surgical procedure whereas 46 patients (35.6%) were diagnosed intraoperatively and 15 (11.6%) were diagnosed preoperatively. Four patients (3.2%) were diagnosed at the autopsy without any surgical interventions and data were missing in 87 patients. 36.7% (18/49 patients) of the patients operated for obstruction were alive at one year, and 15.2% (7/46 patients) at 2-year. Although these percentages are lower than other studies reported in the literature, data was missing in 34 patients, so this might have affected the outcomes. CONCLUSION(S): Small bowel adenocarcinoma should be in the differential diagnosis in patients with longstanding ileal Crohn's disease presenting with small bowel obstruction, anemia, and perforation. Diagnosis and management of the small bowel adenocarcinoma in the setting of Crohn's disease is challenging and awareness and early diagnosis may avoid mortality.

Ustekinumab for Crohn’s disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn’s Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD.Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey–Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn’s disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up.Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up.Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.

Rectal Adenocarcinoma in Crohnʼs Disease: A Case Report

This is a case of a 21 year old male patient who underwent total colectomy and a colostomy for a long standing and extensive Crohns disease who developed rectal adenocarcinoma and eventually expired. In Crohn's disease, cancer risk data is limited. If colorectal cancer does develop, however, the prognosis is recognized to be poor with reduced survival.This 21 year old male presented to our clinic in 2007 at age 13 who was diagnosed with Crohn disease at age 7.His medical history is remarkable with 4 to 5 blood transfusions for anemia, growth hormone deficiency, hypogonadism, vitamin D deficiency and a stable pituitary microadenoma. He was managed with numerous courses of steroids, antimetabolites such as infliximab, certolizumab and 5ASA.His Colonoscopy in 2008 revealed complete loss of vascularity and large pseudo polyps, biopsy was consistent with markedly active chronic colitis with crypt distortion in the colon, marked acute ileitis and acute chronic inflammation in the stomach supporting the diagnosis of Crohn disease .Despite aggressive medical management, his symptoms continued to progress and was hesitant to have an ileostomy over the years .In august 2014 he has failed all medications and was placed on Entyvio.He was having flare ups and recurrent pelvic and abdominal abscess with partial bowel obstruction, perforation of the ileum likely contributed to the abscess and impending fistula. His routine colonoscopy procedure was not successful as there was a large rectal mass which was consistent with malignancy and the biopsy of the rectal mass showed a poorly differentiated infiltrating adenocarcinoma .So, he had diagnostic laparoscopy converted to exploratory laparotomy, extensive lysis of abdomen and pelvic adhesions, drainage of pelvic and abdominal abscesses, ileocectomy and colostomy, eventually deteriorated and expired with rectal adenocarcinoma.Colorectal cancer represents the major cause for excess morbidity and mortality by malignant disease in ulcerative colitis as well as in Crohn's disease. Younger patients with long-standing Crohn's disease should be considered for colonic surveillance to permit earlier diagnosis and treatment of potential colorectal carcinoma. Cancer risk begins to be significant 8 years after the onset of pancolitis (involvement of entire large intestine), or 12-15 years after the onset of left-sided colitis. Colonoscopy every 1 to 2 years with biopsies for dysplasia.3062_A Figure 1. a large rectal mass3062_B Figure 2. Showing large pseudopolyps

Standardization of mesenchymal stromal cell therapy for perianal fistulizing Crohn's disease.

Local administration of mesenchymal stromal cells (MSCs) into the fistula tract seems to improve patient outcome in perianal fistulas due to Crohn's disease (CD). In this paper we propose a standardized and validated protocol for the local administration of MSCs for CD perianal fistulas to be able to reliably assess efficacy. A working group consisting of gastroenterologists and surgeons with expertise in the treatment of perianal CD developed a consensus perianal fistula treatment protocol for local MSC treatment of perianal fistulizing CD. The treatment protocol was validated during a trial of allogeneic bone marrow-derived MSCs for the treatment of refractory perianal Crohn's fistulas. Localization and classification of perianal fistulas with MRI and rectoscopy is of crucial importance prior to surgical intervention with local therapy administration. Examination under anesthesia is necessary to incise and drain abscesses when present. Optimization of medical treatment when active luminal CD is present, is the first step before embarking on surgery and local therapy administration. In addition, strictures preventing the surgeon from adequately performing the surgical procedure have to be endoscopically dilated. Curettage of the fistula tract has an important role as long-standing CD perianal fistulas close poorly without removal of their epithelial lining. To diminish bacterial contamination of the fistula, the internal opening has to be closed. The origin of the fistula is the internal opening, therefore, efficacy of MSCs is presumably the highest when they are injected into the tissue around the internal opening. In this article, we propose a standardized method of local MSC administration for perianal fistulizing CD. The use of this standardized and validated protocol for the administration of local treatment of CD perianal fistulas will allow reliable comparison of the efficacy of local therapies in future.

Dietary intake of patients with inflammatory bowel disease: A comparison with individuals from a general population and associations with relapse

Individuals with inflammatory bowel disease (IBD) often hold strong beliefs on how diet impacts their disease. This study aimed to compare dietary intakes between IBD patients and individuals from the general population and to assess associations of dietary factors with relapse in patients with IBD. Patients with longstanding Crohn's disease and ulcerative colitis (n=165) filled out food frequency questionnaires, as did individuals participating in a Dutch population-based study (controls) (n=1469). Multivariable regression analyses were used to assess differences in habitual dietary intake between IBD patients and controls, and to estimate associations of dietary factors in patients in remission with the development of disease relapse at follow-up. IBD patients had higher intakes of animal protein (3.50g/d, 95% confidence interval (CI) 1.67-5.34) and carbohydrate (10.1g/d, 95% CI 5.23-14.9) than controls and lower intakes of (unsaturated) fat (-3.53g/d, 95% CI-5.57- -1.50), dietary fiber (-2.19g/d, 95% CI-3.05- -1.32) and alcohol (-0.84g/d, 95% CI-1.46- -0.22). This was explained by a higher consumption of carbonated beverages, meat and poultry and lower consumption of fruit, vegetables and dairy products (except cheese) by IBD patients compared with controls. Several dietary factors, particularly (saturated) fat and fiber, appeared to be associated with risk of relapse. IBD patients had higher dietary intakes of (animal) protein and carbohydrate and lower intakes of (unsaturated) fat, dietary fiber and alcohol compared with a general Dutch population. The results further underscore that dietary factors may have a role in disease course.

Issue Highlights

Issue Highlights

Carcinoma in the residual rectum of a long-standing Crohn's disease patient following subtotal colectomy: A case report.

The development of colorectal cancer in long-standing Crohn's disease (CD) patients has become a major complication. Therapeutic guidelines for CD-associated cancer (CDAC) have already been established in Western countries; however, specific guidelines are not currently available in Japan. Surveillance of the residual intestine for cancer screening is important for long-standing CD patients. The present case report describes the occurrence of rectal carcinoma in a patient with a 25-year history of CD. A 37-year-old male with a 17-year history of CD underwent semi-emergent subtotal colectomy and ileostomy for bowel obstruction secondary to the transverse colon stenosis, and multiple severe stenosis and inflammation. Postoperatively, the patient resumed pharmacological treatment and underwent follow-up colonoscopies at ~1-2-year intervals. Despite continued pharmacological treatment, inflammation continued in the residual rectum. A total of 8 years following the primary operation, colonoscopy revealed inflammatory polyposis at the remnant rectum, which was diagnosed as adenocarcinoma. The interval between the last colonoscopy was 16 months. The patient then underwent laparoscopic abdominoperineal resection, and remained without recurrence for 12 months following resection. Thus, in long-standing CD patients, annual colonoscopy of the residual intestine may be considered for cancer screening, and specific surveillance guidelines for CDAC should be established.