Background & Aims: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC). Previous studies concluded that primary sclerosing cholangitis (PSC) is an independent risk factor for CRC in IBD. We aimed to investigate the impact of IBD and PSC on the risk of developing CRC, mortality, and colectomy.

Methods: Patients with IBD diagnosed between 1969 and 2014 were identified from the Swedish National Patient Register, together with 5 matched controls per case from the background population. We estimated the impact of some risk factors including PSC± on the risk of CRC and mortality in the patients with IBD compared with that in the controls, and colectomy within the IBD cohort.

Results: Among all patients with IBD, the hazard ratio (HR) of CRC was 1.83 (95% confidence interval [CI], 1.72–1.96; P < .001). The risk was highest in the PSC+ patients initially but decreased over time. PSC+ patients diagnosed with IBD ≤20 years of age had a highly increased risk with an incidence rate ratio (IRR) of 74.97 (95% CI, 44.7–126.1; P < .001) compared with controls. PSC+ patients had 9 to 16 times higher risk of cancer in cecum/ascending, transverse, and descending colon compared with sporadic CRC among controls. Synchronous cancer was found in 4.7% of PSC+ patients, 4.4% of PSC− patients, and 1.9% among controls (P < .001).

Conclusions: Patients with IBD have an increased risk of CRC, mostly prominent among young PSC+ patients. PSC+ patients display a tendency to develop CRC in the proximal colon and more synchronous CRC. This should be considered when monitoring and counseling patients with IBD.

Introduction: beta-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC. Methods: A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue. Results: Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer. Conclusion: In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location. (c) 2024 The Author(s).Published by S. Karger AG, Basel

Aim: Crohn's anal fistula (CAF) is a complex condition, with no agreement on which patient characteristics should be routinely reported in studies. The aim of this study was to develop a core descriptor set of key patient characteristics for reporting in all CAF research.

Method: Candidate descriptors were generated from published literature and stakeholder suggestions. Colorectal surgeons, gastroenterologists and specialist nurses in inflammatory bowel disease took part in three rounds of an international modified Delphi process using nine-point Likert scales to rank the importance of descriptors. Feedback was provided between rounds to allow refinement of the next ratings. Patterns in descriptor voting were assessed using principal component analysis (PCA). Resulting PCA groups were used to organize items in rounds two and three. Consensus descriptors were submitted to a patient panel for feedback. Items meeting predetermined thresholds were included in the final set and ratified at the consensus meeting.

Results: One hundred and thirty three respondents from 22 countries completed round one, of whom 67.0% completed round three. Ninety seven descriptors were rated across three rounds in 11 PCA-based groups. Forty descriptors were shortlisted. The consensus meeting ratified a core descriptor set of 37 descriptors within six domains: fistula anatomy, current disease activity and phenotype, risk factors, medical interventions for CAF, surgical interventions for CAF, and patient symptoms and impact on quality of life.

Conclusion: The core descriptor set proposed for all future CAF research reflects characteristics important to gastroenterologists and surgeons. This might aid transparent reporting in future studies.

BACKGROUND AND AIMS: Colectomy and reconstruction in patients with inflammatory bowel disease (IBD) may adversely affect fertility, but few population-based studies are available.

METHODS: Fertility was assessed in 2,989 women and 3,771 men with IBD and prior colectomy 1964-2014, identified from the Swedish National Patient Register, and 35,092 matched individuals.

RESULTS: Reconstruction with ileoanal pouch anastomosis (IPAA) was as common as ileorectal anastomosis (IRA) in ulcerative colitis (UC) and IBD-unclassified (IBD-U) while rare in Crohn's disease (CD). Compared with the matched reference cohort, women with IBD had lower fertility overall after colectomy (HR 0.65, CI 0.61-0.69), with least impact leaving the rectum intact (HR 0.79, CI 0.70-0.90). Compared with colectomy only, fertility in female patients remained unaffected after IRA (HR 0.86, CI 0.63-1.17 for UC, 0.86, CI 0.68-1.08 for IBD-U and 1.07, CI 0.70-1.63 for CD), but was impaired after IPAA, especially in UC (HR 0.67CI 0.50-0.88), and after completion proctectomy (HR 0.65, CI 0.49-0.85 for UC, 0.68, CI 0.55-0.85 for IBD-U and 0.61, CI 0.38-0.96 for CD). In men, fertility was marginally reduced post colectomy (HR 0.89, CI 0.85-0.94), regardless of reconstruction.

CONCLUSIONS: Fertility was reduced in women after colectomy for IBD. The least impact was seen when a deviated rectum was left intact. IRA was associated with no further reduction in fertility, whereas proctectomy and IPAA were associated with the strongest impairment. IRA therefore seems to be the preferred reconstruction to preserve fertility in selected female patients. Fertility in men was only moderately reduced after colectomy.

BACKGROUND: Kock’s continent ileostomy is an option after proctocolectomy for patients not suitable for ileal pouch anal anastomosis or ileorectal anastomosis. Ulcerative colitis is the most common indication for continent ileostomy.

OBJECTIVE: The aim of this study was to evaluate the long-term outcome of continent ileostomy.

DESIGN: Retrospective cohort register study.

SETTINGS: Data were obtained from the Swedish National Patient Registry.

PATIENTS: All patients with inflammatory bowel disease and a continent ileostomy were identified. Data on demographics, diagnosis, reoperations, and excisions of the continent ileostomy was obtained. Patients with inconsistent diagnostic coding were classified as inflammatory bowel disease-unclassified.

MAIN OUTCOME MEASURES: The main outcome measures was number of reoperations, time to reoperations and time to excision of continent ileostomy.

RESULTS: We identified 727 patients, 428 (59%) with ulcerative colitis, 45 (6%) with Crohn’s disease and 254 (35%) with inflammatory bowel disease-unclassified. After a median follow-up time of 27 (IQR, 21-31) years 191 (26%) patients had never had revisional surgery. Some 1,484 reoperations were performed on 536 (74%) patients, the median number of reoperations was 1 (IQR, 0-3) per patient. The continent ileostomy was excised in 77 (11%) patients. Reoperation within the first year after reconstruction was associated with higher rate of revisions (IRR, 2.90 p < 0.001) and shorter time to excision (HR 2.38 p < 0.001). Constructing the continent ileostomy after year 2000 was associated with increased revision and excision rates (IRR, 2.7 p < 0.001 and HR 2.74 p = 0.013). Inflammatory bowel disese-unclassified was associated with increased revisions (IRR, 1.3 p < 0.001) and the proportion of IBD-unclassified patients almost doubled from the 1980s (32%) to after 2000 (50%).

LIMITATIONS: Retrospective design, data from register. No data on quality of life available.

CONCLUSION: Continent ileostomy is associated with substantial need for revisional surgery, but most patients get to keep their reconstruction for a long time. See Video Abstract at https://links.lww.com/DCR/C122.

Purpose: Hartmann's reversal is a complex operation with a high morbidity rate. Minimally invasive surgery has been used to reduce the impact of surgery on fragile patients. The aim of this comparative study is to look at the results of Hartmann's reversal procedures with different approaches.

Methods: All the patients who underwent Hartmann's reversal were collected retrospectively (124 cases). Sixty-four patients (50.4%) had an open operation, 6 cases (5%) were treated with a conventional laparoscopic approach, 34 patients (28.1%) underwent single incision laparoscopic surgery (SILS), and 20 (16.5%) required other additional trocars.

Results: SILS operations were slightly longer than the open procedures (175 min vs 150 min), with the same rate of postoperative complications and reoperations (p = 0.83 and p = 0.42), but with a shorter hospital stay (5 days p = 0.007). Age (p = 0.03), long operative time (p = 0.01), and ASA score (p = 0.05) were identified as independent factors affecting postoperative morbidity. The grade of adhesions caused a longer operative time (p = 0.001) and a higher risk of conversion (p < 0.001), and short rectal stump increased the risk of protective loop ileostomy (p = 0.008). Patients with grade 2-3 of adhesions had a longer length of stay (p = 0.05).

Conclusions: Minimally invasive procedures had a shorter hospital stay and did not show any increase in morbidity rate when compared with open cases. Age, longer operative time, and ASA score increased the risk of postoperative complications. Furthermore, patients with a short rectal stump had a higher chance of having a defunctioning ileostomy.

Background and Aims Onset of inflammatory bowel disease (IBD) in men is most common during childbearing age, but little is known about the impact on fertility. Previous studies of fertility in men were small, which justifies this large nation-based registry study. Methods Fertility was assessed in a national cohort of men with IBD aged 15-44 years in 1964-2014, identified from the Swedish National Patient Register, and in a reference cohort matched for age and place of residence (ratio 1:5). Information about childbirths was found in the Swedish Multi-Generation Register. Patients with indeterminate colitis or inconsistent IBD coding were classified as IBD-unclassified (IBD-U). Results The cohorts included 29,104 men with IBD and 140,901 matched individuals. IBD patients had a lower fertility rate (number of births per 1000 person years) compared with the matched individuals; 1.28 (SD 1.27) versus 1.35 (SD 1.31; p &lt; 0.001). Fertility was somewhat impaired in all IBD subtypes compared with the matched cohort; ulcerative colitis (UC) (hazard ratio [HR] 0.93, 95% CI 0.91-0.96), Crohns disease (CD) (HR 0.95, 95% CI 0.92-0.98) and IBD-U 0.92, 95% CI 0.89-0.95. The cumulated total parity and the parity progression were also decreased for all IBD subtypes. Within the IBD cohort disease severity, intensity of medical treatment (CD) and bowel surgery (IBD-U) were further associated with impaired fertility. Conclusions This nationwide cohort study shows only slightly impaired fertility in men with IBD.

Purpose: Small intestinal neuroendocrine tumours (siNETs) with a Ki-67 proliferation index between 3 and 20% belong to WHO grade 2. Response to treatment may be monitored by blood chromogranin A (CgA) and urine 5-hydroxyindoleacetic acid (5HIAA). The aim of this retrospective study was to investigate the prognostic value of baseline CgA and 5HIAA and of the early biochemical response to treatment, and to compare different cut-off values used in the literature.

Methods: A retrospective cohort study of 184 patients with siNET Grade 2 treated with somatostatin analogues (SSA), interferon-alpha (IFN) or peptide receptor radionuclide therapy (PRRT).

Results: Baseline CgA was a statistically significant prognostic marker for both cancer-specific survival (CSS) and progression-free survival (PFS). A cut-off of 5 × ULN (upper limit of normal) was best discriminative in most cases, but 2 × ULN discriminated better for SSA. Baseline 5HIAA was a prognostic marker for CSS in treatment with IFN and PRRT, but not for single SSA. Early changes of CgA and 5HIAA correlated well with CSS (HR 3.18, 95% CI 1.82-5.56 and HR 1.47, 95% CI 1.16-1.86) and PFS (HR 3.08, 95% CI 1.86-5.10 and HR 1.37, 95% CI 1.11-1.68) for SSA, but not for PRRT.

Conclusions: Baseline CgA and to a lesser extent 5HIAA are associated with CSS irrespective of treatment used, and with PFS after PRRT, and 5 × ULN provides best discrimination in many, but not all, cases. Early reductions of CgA and 5HIAA are prognostic for treatment with SSA, but not PRRT.

Background: Leukocytes, such as T cells and macrophages, play an important role in tumorigenesis. CC chemokine ligand (CCL) 4, which is produced by lymphocytes and macrophages, has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes.

Aim: To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer (CRC) and evaluate their prognostic significance.

Methods: Luminex technology was used to determine CCL4 Levels in CRC tissue (n = 98), compared with paired normal tissue, and in plasma from patients with CRC (n = 103), compared with healthy controls (n = 97). Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery, Ryhov County Hospital, Jönköping, Sweden. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue (n = 101). Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls.

Results: The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue (90%, P < 0.001 and 45%, P < 0.05, respectively). CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease. Low CCL4 protein expression levels in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients (P < 0.01). The level of plasma CCL4 was 11% higher in CRC patients than in healthy controls (P < 0.05) and was positively correlated (r = 0.56, P < 0.01) with the CCL4 protein level in CRC tissue. The analysis of CCL4 gene polymorphism rs10491121 showed a difference (P < 0.05) between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease. Moreover, the rate of the A allele was higher among CRC patients with mucinous cancer than among those with non-mucinous cancer.

Conclusion: The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121, particularly in the right colon, are associated with clinical outcome in CRC patients.

Background and Aims: Inflammatory bowel disease [IBD] has been associated with reduced female fertility. We analyse fertility in a national cohort of women with IBD.

Methods: Fertility was assessed in women with IBD aged 15-44 years in 1964-2014, identified from the Swedish National Patient Register and a matched cohort [ratio 1:5]. Patients with indeterminate colitis or inconsistent IBD coding were classified as IBD-unclassified [IBD-U].

Results: The cohorts included 27 331 women with IBD and 131 892 matched individuals. The fertility rate in IBD was 1.52 (standard deviation [SD] 1.22) births per 1000 person-years and 1.62 [SD 1.28] [p&lt;0.001] in matched individuals. Fertility was impaired in all IBD subtypes compared with the matched cohort (hazard ratio Crohns disease [CD] 0.88, 95% confidence interval [CI] 0.85-0.91; IBD-U 0.86, 95% CI 0.83-0.89; and ulcerative colitis [UC] 0.96, 95% CI 0.93-0.98). Fertility improved during the study period for the IBD cohort except for CD. Parity progression ratio, the proportion of IBD women progressing from one parity to the next compared with the matched cohort, was decreased at all parity levels for CD and IBD-U, but only for multiparous women in UC. Contraceptive usage was higher in IBD, both before and after the diagnosis. Disease severity, bowel resections, and perianal disease in CD affected fertility negatively.

Conclusions: Fertility was impaired mainly in women with CD and IBD-U, and less so in UC. During the study period, fertility improved in women with UC or IBD-U. Some results suggest a role of voluntarily reduced fertility.