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.

A systemic review and metaanalysis of postoperative outcomes in urgent and elective bowel resection in patients with Crohn's disease.

PURPOSE: The study examined whether urgency of surgical intervention affects postoperative outcomes in patients with Crohn's disease (CD) undergoing bowel resection. METHOD: The review was conducted according to a predefined, published study protocol in Prospero which is an international database of prospectively registered systematic reviews in health. The study reported according to PRIMSMA guidelines. We searched Embase and Pubmed for articles reporting postoperative outcome after urgent and elective surgery in patients with CD undergoing bowel resection. Primary outcome variable was 30-day overall postoperative complications while secondary outcome variables were intraabdominal septic complications (IASCs), mortality, reoperation, and readmission. Assessment of bias was performed using Newcastle-Ottawa score. Two authors independently extracted data on each study, patients, and outcome measures. RESULTS: The search identified 22 studies in which 955 patients underwent urgent surgeries while 6518 patients underwent elective surgeries. Based on the quality assessment, 19 studies were classified as having high risk of bias, one study as having a medium risk of bias and 2 studies as having low risk of bias (≥ 8 stars). Random-effect metaanalysis showed urgent surgery was associated with ~ 40% increase in overall complications compared to elective surgery (RR = 1.43, 95% CI [1.09; 1.87], p = 0.010). IASCs also increased in patients who had urgent surgery (RR = 1.44, 95% CI [1.08; 1.92], p = 0.013). No significant difference was shown in mortality and readmission rates. CONCLUSION: Urgent bowel resection in patients with CD is associated with higher risk of overall postoperative complications and IASCs.

The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer.

Epigenetic alterations in colorectal cancer (CRC) cause important differences in the underlying tumor biology and aggressiveness. DNA hypermethylation is central for the development of CRC but the prognostic impact remains elusive. We aimed to assess the association between cell-free hypermethylated DNA and stage and survival in colorectal cancer (CRC). We analyzed pre-treatment plasma samples from 193 patients with CRC. Thirty gene-promoter regions were analyzed using methylation specific PCR. We compared the median number (range) of hypermethylated promoter regions with CRC stage, and constructed a multivariable Cox-regression model adjusted for stage, to evaluate the added prognostic information. The median number of hypermethylated promoter regions was nine (0-28) in patients with distant metastasis compared to five (0-19) in patients without metastatic disease (p < 0.0001). The majority of the hypermethylated promoter regions inferred a poor prognosis. Cox-regression analysis adjusted for patient age, sex, pre-treatment CEA-levels, and disease stage, showed that RARB (HR = 1.99, 95% CI [1.07, 3.72]) and RASSF1A (HR = 3.35, 95% CI [1.76, 6.38]) hypermethylation inferred a significant effect on survival. The risk of metastasis increase with the number of cell-free hypermethylated promoter regions. The presence of RARB and RASSF1A hypermethylation indicated aggressive disease, regardless of stage at the time of diagnosis.

Hepatic artery aneurysm causing gastrointestinal haemorrhage - Case report and literature review.

INTRODUCTION: True hepatic artery aneurysms (HAAs) are rare, and when complicated by gastrointestinal haemorrhage, it becomes an even rarer disease entity. The mortality is high and imaging may fail to provide the diagnosis. We present a case of a true hepatic artery aneurysm complicated by a fistula to the duodenum which was first recognised during surgery. PRESENTATION OF CASE: A 77-year-old man presented with upper gastrointestinal haemorrhage. Upper endoscopy revealed an ulceration in the duodenal bulb, which was refractory to endoscopic treatment. Computed tomography and angiography did not reveal the source of haemorrhage and as such, the diagnosis was delayed, until laparotomy was performed. Resection of the HAA and graft placement resulted in complete haemostasis. DISCUSSION: True hepatic aneurysms communicating with the gastrointestinal tract have only been presented in case reports and short case series. Arteriosclerosis is a relatively common risk factor, but the underlying pathology is unknown. Meanwhile, gastrointestinal haemorrhage is a symptom of other, more common diseases in the gastrointestinal tract, and these factors, complicate the diagnostic workup. CONCLUSION: In the case of treatment refractory duodenal haemorrhage, a visceral aneurysm should be considered. Even though angiography is performed, a HAA may remain undetected due to bleeding cessation. Improved computed tomography modalities could aid in the detection of gastrointestinal haemorrhage from HAAs, and ensure timely treatment by endovascular methods or surgery if the diagnosis is kept in mind in the initial evaluation.

Hypermethylated DNA, a circulating biomarker for colorectal cancer detection.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the western world. Screening is an efficient method of reducing cancer-related mortality. Molecular biomarkers for cancer in general and CRC in particular have been proposed, and hypermethylated DNA from stool or blood samples are already implemented as biomarkers for CRC screening. We aimed to evaluate the performance of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC detection. METHODS: We conducted a cross-sectional case-control study of 193 CRC patients and 102 colonoscopy-verified healthy controls. Using methylation specific polymerase chain reaction, we evaluated 30 DNA promoter regions previously found to be CRC specific. We used multivariable logistic regression with stepwise backwards selection, and subsequent leave-pair-out cross validation, to calculate the optimism corrected area under the receiver operating characteristics curve (AUC) for all stage as well as early stage CRC. RESULTS: None of the individual DNA promoter regions provided an overall sensitivity above 30% at a reasonable specificity. However, seven hypermethylated promoter regions (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5% specificity using a cut point value of 0.5. CONCLUSIONS: Individual hypermethylated DNA promoter regions have limited value as CRC screening markers. However, a panel of seven hypermethylated promoter regions show great promise as a model for CRC detection.

Rectal Hodgkin lymphoma in a patient with ulcerative colitis: a case study.

A case of Hodgkin lymphoma located in the rectum of a patient with ulcerative colitis is described. The patient was a 44 year old male treated with thiopurines for ulcerative colitis for ten years. He was admitted with malaise, weight loss and abdominal pain. Endoscopy revealed a large ulcerative lesion involving the rectum and distal part of the sigmoid colon. Although it macroscopically resembled a rectal cancer, repeated biopsies did not reveal any malignancy. In order to resolve the symptoms of stenosis and to get the final diagnosis a recto-sigmoid resection was performed. Pathologic examination revealed nodular sclerosis classical Hodgkin lymphoma, positive for Epstein Barr Virus. Subsequent examination revealed disseminated disease involving the pelvic wall, liver, and bone marrow. The patient is currently receiving chemotherapeutic treatment, and follow-up shows disease remission.Hodgkin lymphoma associated with immunosuppressive therapy is rare. However, patients with ulcerative colitis receiving such treatment are at increased risk of lymphoproliferative disordes, potentially due to loss of immunosurveillance and presence of oncogenic viruses (i.e. Epstein-Barr virus). Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6156776351558952.