No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial.

OBJECTIVES: Opioids used to manage severe pain in acute pancreatitis might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia. METHODS: This double-blind, randomized, placebo-controlled trial included adult patients with acute pancreatitis and systemic inflammatory response syndrome at four Danish centers. Participants were randomized to receive five days of continuous intravenous methylnaltrexone (0.15mg/kg/day) or placebo added to the standard of care. The primary endpoint was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality. RESULTS: In total, 105 patients (54% males) were randomized to methylnaltrexone (n=51) or placebo (n=54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference, 3.8 [95% CI, -40.1 to 47.6]; P=0.87). At 48 hours, we found no differences between groups in pain severity (0.0 [95% CI, -0.8 to 0.9]; P=0.94), pain interference (-0.3 [95% CI, -1.4 to 0.8]; P=0.55), and morphine equivalent doses (6.5 mg [95% CI, -2.1 to 15.2]; P=0.14). Methylnaltrexone also did not affect the risk of severe disease (8% [95% CI, -11 to 28]; P=0.38) and mortality (6% [95% CI, -1 to 12]; P=0.11). The medication was well-tolerated. CONCLUSIONS: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of acute pancreatitis.

Monocyte recruitment in venous pulmonary embolism at time of cancer diagnosis in upper gastrointestinal cancer patients.

Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system.

Exploring D-Lactate as a Biomarker for Acute Intestinal Necrosis in 2958 Patients: A Prospective Cross-Sectional Study.

BACKGROUND: Timely diagnosis of acute intestinal necrosis (AIN) is lifesaving, but challenging due to unclear clinical presentation. D-lactate has been proposed as an AIN biomarker. OBJECTIVES: We aimed to test the diagnostic performance in a clinical setting. METHODS: We performed a cross-sectional prospective study, including all adult patients with acute referral to a single tertiary gastrointestinal surgical department during 2015-2016 and supplemented by enrollment of high-risk in-hospital patients suspected of having AIN during 2016-2019. AIN was verified intraoperatively, and D-lactate was analyzed using an automatic spectrophotometric set-up. A D-lactate cut-off for AIN was estimated using the receiver operating characteristic curve. The performance according to patient subgroups was estimated using the area under the receiver operating characteristic curve (AUC). Given the exploratory nature of this study, a formal power calculation was not feasible. RESULTS: Forty-four AIN patients and 2914 controls were enrolled. The D-lactate cut-off was found to be 0.0925 mM. Due to lipemic interference, D-lactate could not be quantified in half of the patients, leaving 23 AIN patients and 1456 controls for analysis. The AUC for the diagnosis of AIN by D-lactate was 0.588 (95% confidence interval 0.475-0.712), with a sensitivity of 0.261 and specificity of 0.892. Analysis of high-risk patients showed similar results (AUC 0.579; 95% confidence interval 0.422-0.736). CONCLUSION: D-lactate showed low sensitivity for AIN in both average-risk and high-risk patients. Moreover, lipemic interference precluded valid spectrophotometric assessment of D-lactate in half of the patients, further disqualifying the clinical utility of D-lactate as a diagnostic marker for AIN.

Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with stage III or IV pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma remains one of the major causes of cancer-related mortality globally. Unfortunately, current prognostic biomarkers are limited, and no predictive biomarkers exist. This study examined promoter hypermethylation of secreted frizzled-related protein 1 (phSFRP1) in cfDNA as a prognostic biomarker and predictor of treatment effect in patients with metastatic FOLFIRINOX-treated PDAC and locally advanced PDAC. METHODS: We performed methylation-specific PCR of the SFRP1 genes' promoter region, based on bisulfite treatment. Survival was assessed as time-to-event data using the pseudo-observation method and analyzed with Kaplan-Meier curves and generalized linear regressions. RESULTS: The study included 52 patients with FOLFIRINOX-treated metastatic PDAC. Patients with unmethylated (um) SFRP1 (n = 29) had a longer median overall survival (15.7 months) than those with phSFRP1 (6.8 months). In crude regression, phSFRP1 was associated with an increased risk of death of 36.9% (95% CI 12.0%-61.7%) and 19.8% (95% CI 1.9-37.6) at 12 and 24-months, respectively. In supplementary regression analysis, interaction terms between SFRP1 methylation status and treatment were significant, indicating reduced benefit of chemotherapy. Forty-four patients with locally advanced PDAC were included. phSFRP1 was associated with an increased risk of death at 24-months CONCLUSIONS: This indicates that phSFRP1 is a clinically useful prognostic biomarker in metastatic PDAC and possibly in locally advanced PDAC. Together with existing literature, results could indicate the value of cfDNA-measured phSFRP1 as a predictive biomarker of standard palliative chemotherapy in patients with metastatic PDAC. This could facilitate personalized treatment of patients with metastatic PDAC.

The effect of antithrombotic treatment on the fecal immunochemical test for colorectal cancer screening: a nationwide cross-sectional study.

BACKGROUND : Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC. METHODS : This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression. RESULTS : Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56-1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48-2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %-6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %-6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51-0.66]). CONCLUSION : Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening.

Exploring I-FABP, endothelin-1 and L-lactate as biomarkers of acute intestinal necrosis: a case-control study.

OBJECTIVE: Acute intestinal necrosis (AIN) is a disease with devastating high mortality. AIN due to obstructed arterial blood flow has a blurred clinical presentation. Timely diagnosis is paramount, and a blood-based biomarker is warranted to increase patient survival. We aimed to assess intestinal fatty acid binding protein (I-FABP) and endothelin-1 as diagnostic biomarkers for AIN. To our knowledge, this is the first study exploring endothelin-1 in AIN patients from a general surgical population. DESIGN: We conducted a single-centre nested case-control study comparing acutely admitted AIN patients to age- and sex-matched non-AIN patients during 2015-2016. I-FABP and endothelin-1 were analysed using an enzyme-linked immunosorbent assay. L-lactate levels were also measured in all patients. Cut-offs were estimated using receiver operator characteristic curves, and the diagnostic performance was estimated using the area under the receiver operator characteristic curve (AUC). RESULTS: We identified 43 AIN patients and included 225 matched control patients. Median levels of I-FABP, endothelin-1 and L-lactate were 3550 (IQR: 1746-9235) pg/ml, 3.91 (IQR: 3.33-5.19) pg/ml and 0.92 (IQR: 0.74-1.45) mM in AIN patients and 1731 (IQR: 1124-2848) pg/ml, 2.94 (IQR: 2.32-3.82) pg/ml and 0.85 (IQR: 0.64-1.21) mM in control patients, respectively. The diagnostic performances of endothelin-1 and of I-FABP + endothelin-1 combined were moderate. Endothelin-1 alone revealed an AUC of 0.74 (0.67; 0.82). The sensitivity and specificity of endothelin-1 were 0.81 and 0.64, respectively. CONCLUSION: I-FABP and endothelin-1 are promising biomarkers for AIN, with moderate diagnostic performance compared with the commonly used biomarker L-lactate. PREREGISTRATION: ClinicalTrials.gov: NCT05665946.

Bowel dysfunction following pelvic organ cancer: a prospective study on the treatment effect in nurse-led late sequelae clinics.

BACKGROUND: Bowel dysfunction following treatment of pelvic organ cancer is prevalent and impacts the quality of life (QoL). The present study aimed to evaluate the feasibility and effects of treating bowel dysfunction in two nurse-led late sequelae clinics. MATERIAL AND METHODS: Treatment effects were monitored prospectively by patient-reported outcome measures collected at baseline and discharge. Change in bowel function was evaluated by 15 bowel symptoms, the St. Mark's Incontinence Score, the Patients Assessment of Constipation-Symptoms (PAC-SYM) score and self-rated bowel function. QoL was evaluated by the EuroQol 5-dimension 5-level (EQ-5D-5L) utility score and by measuring the impact of bowel function on QoL. RESULTS: From June 2018 to December 2021, 380 cancer survivors (46% rectal, 15% gynaecological, 13% anal, 12% colon, 12% prostate, and 2% other cancers) completed a baseline questionnaire and started treatment for bowel dysfunction. At referral, 96% of patients were multisymptomatic. The most frequent symptoms were faecal urgency (95%), fragmented defaecation (93%), emptying difficulties (92%), flatus/faecal incontinence (flatus 89%, liquid 59%, solid 33%), and obstructed defaecation (79%). In total, 169 patients were discharged from the clinics in the follow-up period. At discharge, 69% received conservative treatment only and 24% also received transanal irrigation; 4% were surgically treated; 3% discontinued treatment. Improvements were seen in all 15 bowel symptoms (p < 0.001), the mean St. Mark's Incontinence Score (12.0 to 9.9, p < 0.001), the mean PAC-SYM score (1.04 to 0.84, p < 0.001) and the mean EQ-5D-5L utility score (0.78 to 0.84, p < 0.001). Self-rated bowel function improved in 56% (p < 0.001) of cases and the impact of bowel function on QoL improved in 46% (p < 0.001). CONCLUSION: Treatment of bowel dysfunction in nurse-led late sequelae clinics is feasible and significantly improved bowel function and QoL.

Prospective evaluation of bowel function and quality of life after colon cancer surgery - is it time for routine screening for late sequelae?

AIM: Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery. METHOD: CC patients undergoing surgical resection in 2018-2020 at five surgical departments were included in this population-based prospective cohort study. Included patients completed electronic surveys consisting of a collection of validated scores 3 m and 12 m after surgery. RESULTS: A total of 708 CC patients (423 RightSCR, 285 LeftSCR) were included. In RightSCR, no improvement was observed from 3 m to 12 m in most scores/items, on the contrary, symptom worsening in flatus- and faecal incontinence and urgency was observed (p < 0.05). Also, the proportion of patients rating their bowel function as very good/good decreased (p < 0.05) in this group. In LeftSCR improvement was found in flatus and faecal incontinence, urgency and night-time defaecation (p < 0.02), while no improvement was observed in the remaining scores/items. At 12 m, higher proportions of RightSCR than LeftSCR reported loose stools, incontinence and urgency (all p < 0.001), whereas LeftSCR more often reported hard stools and flatus incontinence (p < 0.05). Among all CC patients 18.3% reported bowel-related impairment of QoL at 12 m with no differences between the two groups. CONCLUSION: From 3 m to 12 m no significant change was observed in the majority of bowel function and QoL scores/items, however, some symptoms worsened in RightSCR, while a few improved in LeftSCR. Bowel dysfunction and impaired QoL were still common in both groups at 12 m, although the symptom pattern differed between the groups. These findings call for a systematic screening for bowel dysfunction to ensure early treatment of symptoms.

Diet and bowel symptoms among colon cancer survivors.

BACKGROUND: Survival from colon cancer (CC) has improved considerably over the last decades, yet many survivors suffer from late sequelae from treatment. Typical symptoms of bowel dysfunction after treatment of CC are diarrhea, urge for defecation, fecal incontinence, bloating and constipation. Most CC survivors make dietary changes to alleviate bowel symptoms. We aimed to describe the self-perceived effects of diet on bowel function among CC survivors and the level of dietary information given. MATERIALS AND METHODS: In this cross-sectional study, CC patients from four surgical departments in Denmark completed surveys regarding the effects of diet on their bowel function and whether they had previously received dietary advice. Data concerning sociodemographic characteristics and the surgical procedure (right-sided or left-sided hemicolectomy) were collected from the Danish Colorectal Cancer Group database. Forty-four healthcare professionals specialized in CC completed a questionnaire on how they advise CC. Descriptive statistics were applied. RESULTS: Among 1544 patients invited, 1239 (80.4%) responded, and 844 met the inclusion criteria (53% males, median age 72.6 years, median time since surgery 742 days). Among these, 267 (32%) reported that food affected bowel function. Fat was perceived to have a negative effect in 193 (25%), spices in 149 (19%), sweets in 101 (13%) and meat in 99 (13%). There was no association between tumor site and food categories affecting bowel function (p = 0.078). Most healthcare professionals (93%) stated that their unit gave advice about diet, but only 24% of patients remembered such information. CONCLUSION: One-third of CC survivors perceive that food items, especially fat and spices have a negative impact on their bowel function. We found a major discrepancy between healthcare professionals reporting that they provide advice and the proportion of patients remembering this. There is an unmet need for further recognition of the role of diet in CC rehabilitation and for intervention studies of treatment principles.

Microscopic Colitis Patients Possess a Perturbed and Inflammatory Gut Microbiota.

BACKGROUND: Microscopic colitis (MC), an inflammatory disease of the colon, is characterized by chronic non-bloody diarrhea with characteristic inflammation and for some, collagen deposits in mucosal biopsies. The etiology of MC is unclear, although previous findings implicate luminal factors and thus the gut microbiome. However, the relationships between fecal microbiota and MC are relatively unexplored. METHODS: Stool microbiota of MC (n = 15) and healthy controls (HC; n = 21) were assessed by 16S rRNA V4 amplicon sequencing and analysis performed in QIIME. Gut microbiota functions were predicted using Piphillin and inflammatory potential assessed using an in vitro HT29 colonocyte cell assay. RESULTS: MC patient fecal microbiota were less diverse (Faiths index; p < 0.01) and compositionally distinct (PERMANOVA, weighted UniFrac, R2 = 0.08, p = 0.02) compared with HC subjects. MC microbiota were significantly depleted of members of the Clostridiales, enriched for Prevotella and more likely to be dominated by this genus (Chi2 = 0.03). Predicted pathways enriched in MC microbiota included those related to biosynthesis of antimicrobials, and sphingolipids, to glycan degradation, host defense evasion, and Th17 cell differentiation and activation. In vitro, exposure of cultured colonocytes to cell-free products of MC patient feces indicates reduced gene expression of IL-1B and occludin and increased GPR119 and the lymphocyte chemoattractant CCL20. CONCLUSION: MC gut microbiota are distinct from HC and characterized by lower bacterial diversity and Prevotella enrichment and distinct predicted functional pathways. Limited in vitro experiments indicate that compared with cell-free products from healthy fecal microbiota, MC microbiota induce distinct responses when co-cultured with epithelial cells, implicating microbiota perturbation in MC-associated mucosal dysfunction.

Proteomic Characterization of Colorectal Cancer Tissue from Patients Identifies Novel Putative Protein Biomarkers.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death over the world. There is a great need for biomarkers capable of early detection and as targets for treatment. Differential protein expression was investigated with two-dimensional gel electrophoresis (2D-PAGE) followed by identification with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in CRC patient tissue from (i) the peripheral part of the tumor, (ii) the central part of the tumor as well as from (iii) a non-involved part of the colorectal tissue. The expression patterns of six identified proteins were further evaluated by one-dimensional Western blot (1D-WB) analysis of the CRC tissue. Proteins that were perturbed in expression level in the peripheral or in the central part of the tumor as compared with the non-involved part included S100A11, HNRNPF, HNRNPH1 or HNRNPH2, GSTP1, PKM and FABP1. These identified markers may have future diagnostic potential or may be novel treatment targets after further evaluation in larger patient cohorts.

Irreversible electroporation of pancreatic cancer - Effect on quality of life and pain perception.

BACKGROUND: Most pancreatic cancer (PC) patients are incurable and may need palliative treatment at some point in time. Irreversible electroporation (IRE) is a novel ablative treatment, which aims to provide local tumor control. The aim of this study was to examine how consolidative treatment with IRE affects quality of life (QOL) and pain perception (PP) in patients with non-metastatic pancreatic cancer. METHODS: Secondary outcomes were extracted from a prospective cohort of non-metastatic PC patients treated with IRE from 2013 to 2019. Patients filled in two questionnaires examining QOL and PP at different timepoints during treatment and follow-up. Data from a selected panel of subscales were extracted and analyzed using a mixed random intercept regression model. RESULTS: Subscales from 41 patients at four different timepoints were included in the model. Global health status, physical functioning, fatigue, nausea and vomiting, appetite loss and mean pain interference were negatively impacted (p < 0.05) in the short- and mid-term, corresponding to a low or moderate clinical effect size. However, all negative effects showed a tendency to dissipate over time. CONCLUSIONS: IRE treatment negatively impacted QOL and PP in the short- and mid-term. No positive long-term effects of IRE were found.

Cell-free DNA promoter hypermethylation as a diagnostic marker for pancreatic ductal adenocarcinoma - An external validation study.

BACKGROUND: We recently identified a diagnostic prediction model based on promoter hypermethylation of eight selected genes in plasma cell-free (cf) DNA, which showed promising results as a diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to validate this biomarker profile in an external patient cohort and examine any additional effect of serum CA 19-9. METHODS: Patients with PDAC (n = 346, stage I-IV) and chronic pancreatitis (n = 25) were included. Methylation-specific PCR of a 28-gene panel was performed on serum cfDNA samples. The previously developed diagnostic prediction model (age>65 years, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) was validated alone and in combination with serum CA 19-9 in this external patient cohort. RESULTS: Patients with PDAC had a higher number of hypermethylated genes (mean 8.11, 95% CI 7.70-8.52) than patients with chronic pancreatitis (mean 5.60, 95% CI 4.42-6.78, p = 0.011). Validation of the diagnostic prediction model yielded an AUC of 0.77 (95% CI 0.69-0.84). The combination of serum CA 19-9 and our test had an AUC of 0.93 (95% CI 0.89-0.96) in the primary study and 0.85 (95% CI 0.79-0.91) in the validation study. CONCLUSION: In this validation study, PDAC was associated with a higher number of hypermethylated genes in serum cfDNA than chronic pancreatitis. Our diagnostic test was superior to the predictive value of serum CA 19-9 alone in both the primary and the validation study. The combination of our test with CA 19-9 may serve as a clinically useful diagnostic biomarker for PDAC.

Systematic screening for late sequelae after colorectal cancer-a feasibility study.

AIM: The aim of this study was to test the feasibility of a new method for systematic screening for late sequelae (LS) following colorectal cancer treatment. METHOD: Patients with colorectal cancer from five Danish hospitals were invited to complete a survey about LS at 3, 12, 24 and 36 months after surgery as part of their follow-up. The survey consisted primarily of validated tools, supplemented by a few ad hoc items, measuring bowel, urinary and sexual dysfunction, pain and quality of life and an additional question regarding request for contact. Patients completed surveys electronically or on paper. RESULTS: Of the 1721 invited patients, 1386 (80.5%) were included (1085 with colon cancer and 301 with rectal cancer) of whom 72.5% responded electronically. Patients responding electronically were 7.6 years younger than those responding on paper (P < 0.001). Since some patients answered more than once, the dataset consisted of 2361 surveys. Patients with colon cancer requested phone contact in 19.0% of the surveys, and 8.4% were referred to treatment for LS, primarily bowel dysfunction. Among patients with rectal cancer, 30.8% requested phone contact and 16.2% were referred for treatment of LS, mainly due to bowel and sexual dysfunction. CONCLUSION: This is the first paper investigating a new method of systematic screening for LS following colorectal cancer using electronic patient-reported outcome measures. The study shows that in the Danish population a high response rate can be obtained with this method and that close to three-quarters of patients respond electronically. Patients with rectal cancer had a higher need for phone contact and treatment of LS than patients with colon cancer.

Long-term gastrointestinal sequelae in colon cancer survivors: prospective pilot study on identification, the need for clinical evaluation and effects of treatment.

AIM: The aim of the present pilot study was to describe the type and frequency of long-term gastrointestinal symptoms within a well-defined cohort of colon cancer survivors, their wish for clinical evaluation and treatment outcomes. METHOD: A screening survey was sent to colon cancer survivors 12, 24 and 36 months after surgery. Based on their main symptoms, patients who wished to have a consultation were referred to the gastroenterological or surgical unit of our late cancer sequelae clinic. Treatment effect was monitored by questionnaires on bowel symptoms and the EuroQol five-dimensional (EQ-5D) quality-of-life score. RESULTS: Overall, 953 patients who had survived colon cancer received the screening survey and 767 replied (response rate 80.5%). Of these, 76 (9.9%; 95% CI 7.9%-12.2%) were referred for algorithm-based clinical evaluation and treatment of bowel dysfunction. The majority were women (69.7%) who had undergone a right-sided colonic resection (65.8%). Patients reported various symptoms, mainly including urgency, fragmented defaecation, loose stools and incontinence for liquid stools. Patients with emptying difficulties and low anterior resection syndrome-like symptoms were referred to the surgical unit and patients with diarrhoea were referred to the gastroenterological unit for clinical work-up. Our main endpoint, mean EQ-5D index after treatment, was improved compared with baseline (baseline 0.809, after treatment 0.846; p = 0.049). After treatment, self-rated bowel function and several bowel symptoms were improved as well. CONCLUSION: This study highlights the importance of identifying colon cancer survivors in need of treatment of late gastrointestinal sequelae and clinical management in a multidisciplinary team setting.

Fully automatic d-lactate assay using a modified commercially available method.

Intestinal infarction is the fast-evolving endpoint of impaired blood perfusion to an intestinal segment which may have fatal outcome. Early diagnosis and treatment within 6 h reduce mortality. Currently, d-lactate is a promising biomarker, however, not available in the acute clinical setting. The aim of this study is implementation of d-lactate analysis in a routine clinical setting. We used a spectrophotometric method, based on enzymatic oxidation of d-lactate by d-lactate dehydrogenase (D-LDH) coupled to the reduction of nicotinamide-adenine dinucleotide (NAD+). The amount of NADH formed in this reaction is equivalent to d-lactate. The primary concern in this method is interfering NADH formed by oxidation of l-lactate by l-lactate dehydrogenase (L-LDH). A commercially available kit for d-lactate measurement was implemented on our existing automated routine laboratory equipment including pH-inactivation of L-LDH. Our setup fulfilled clinical quality goals. We were able to measure d-lactate with an acceptable performance of the analysis and a short turn-around time. The method can be used to distinguish between the expected cut-off for intestinal ischemia around 0.3 mM and the upper reference limit of 0.05 mM. With a turnaround time of just 9 min, the analysis has potential as a readily available detection of circulating d-lactate for early diagnosis of intestinal ischemia.

Danish guidelines for management of non-APC-associated hereditary polyposis syndromes.

Hereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes.. The diagnosis entails surveillance from an early age, but universal guideline on how to manage and surveille these new syndromes are lacking. This paper represents a condensed version of the recent guideline (2020) from a working group appointed by the Danish Society of Medical Genetics and the Danish Society of Surgery on recommendations for the surveillance of patients with hereditary polyposis syndromes, including rare polyposis syndromes.

Clinical results and microbiota changes after faecal microbiota transplantation for chronic pouchitis: a pilot study.

Objectives: Research evidence suggests that chronic pouchitis is associated with intestinal dysbiosis. Faecal microbiota transplantation (FMT) has been proposed as a possible treatment. We performed a 6-month prospective, open-label, single-centre cohort pilot-study (NCT03538366) to investigate if FMT could improve clinical outcome and alter gut microbiota in patients with chronic pouchitis.Materials and methods: Nine adult patients with chronic pouchitis were included and allocated to 14 days FMT by enemas from five faecal donors, with a 6-month follow-up. Pouchitis severity was assessed using pouchitis disease activity index (PDAI) before and after FMT. Changes in gut microbiota, and engraftment of donor's microbiota were assessed in faecal samples.Results: All patients were treated with FMT for 14 continuous days. Overall, four of nine patients receiving FMT were in clinical remission at 30-day follow-up, and three patients remained in remission until 6-month follow-up. Clinical symptoms of pouchitis improved significantly between inclusion and 14-day follow-up (p = .02), but there was no improvement in PDAI between inclusion (mean 8.6) and 30-day follow-up (mean 5.2). Treatment with FMT caused a substantial shift in microbiota and increased microbial diversity in six patients, resembling that of the donors, with a high engraftment of specific donor microbiota.Conclusions: Symptomatic benefit in FMT treatment was found for four of nine patients with chronic pouchitis with increased microbial diversity and high engraftment of donor's microbiota. A larger, randomised controlled study is required to fully evaluate the potential role of FMT in treating chronic pouchitis.

Consumption of yoghurt favours remission after faecal microbiota transplantation for chronic pouchitis.

PURPOSE: The gut microbiota is conceivably a key factor in the aetiology of pouchitis. Faecal microbiota transplantation (FMT) has been suggested as a promising new treatment for chronic pouchitis, where treatment options often are few. However, little is known about the influence of the diet on the clinical effects of FMT. We assessed the diet of patients with chronic pouchitis undergoing FMT to investigate the influence of diet on the clinical outcome after FMT. METHODS: Nine patients with chronic pouchitis were allocated to treatment with FMT delivered by enema from five faecal donors for 14 consecutive days in a 6-month prospective, open-label, single-centre cohort pilot study. A dietary questionnaire was completed at baseline for all patients and donors. Patients underwent a pouchoscopy at baseline and at 30-day follow-up, and the Pouchitis Disease Activity Index (PDAI) was assessed. RESULTS: Patients' diets were generally similar, when comparing patients in remission post-FMT (PDAI < 7) with those who relapsed (PDAI ≥ 7). Consumption of grains trended to be different between the two groups (p = 0.06), where patients in relapse consumed more bread products than did patients in remission. However, consumption of yoghurt was significantly different between the two groups (p = 0.04), with patients in remission consuming more yoghurt (mean 1.1 s/d vs 0.2 s/d). CONCLUSION: Gastroenterologist performing clinical studies on FMT for chronic pouchitis should be aware of dietary habits as contributing factors for the clinical effect of FMT.

Proteomic Characterization of Colorectal Cancer Cells versus Normal-Derived Colon Mucosa Cells: Approaching Identification of Novel Diagnostic Protein Biomarkers in Colorectal Cancer.

In the western world, colorectal cancer (CRC) is the third most common cause of cancer-related deaths. Survival is closely related to the stage of cancer at diagnosis striking the clinical need for biomarkers capable of early detection. To search for possible biological parameters for early diagnosis of CRC we evaluated protein expression for three CREC (acronym: Cab45, reticulocalbin, ERC-55, calumenin) proteins: reticulocalbin, calumenin, and ERC-55 in a cellular model consisting of a normal derived colon mucosa cell line, NCM460, and a primary adenocarcinoma cell line of the colon, SW480. Furthermore, this cellular model was analyzed by a top-down proteomic approach, 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for novel putative diagnostic markers by identification of differentially expressed proteins between the two cell lines. A different colorectal carcinoma cell line, HCT 116, was used in a bottom-up proteomic approach with label-free quantification (LFQ) LC-MS/MS. The two cellular models gave sets of putative diagnostic CRC biomarkers. Various of these novel putative markers were verified with increased expression in CRC patient neoplastic tissue compared to the expression in a non-involved part of the colon, including reticulocalbin, calumenin, S100A6 and protein SET. Characterization of these novel identified biological features for CRC patients may have diagnostic potential and therapeutic relevance in this malignancy characterized by a still unmet clinical need.