Hans B. Rahr

Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals

Abstract Objective. The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis. Material and methods. Individuals (n = 4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included. Baseline data and concurrent diseases were recorded. The primary endpoint was detection of CRC and findings at examinations were recorded using International Classification of Diseases-10 codes. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of all individuals. Results. Findings were based on sigmoidoscopy in 1766 and colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas and 1176 with non-neoplastic findings were also detected. The biomarker levels were increased in a variety of diseases including CRC compared to individuals without any findings at endoscopy. A multivariable analysis demonstrated that both markers were significant and independent detectors of CRC. Combining both biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) = 1.8 (95% confidence interval (CI): 1.4–2.2), p < 0.0001; CEA < 5 ng/ml, OR = 1.6, 1.3–1.9, or ≥5 ng/ml, OR = 2.3, 95% CI: 1.9–2.7 (p < 0.0001)) were obtained. Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint showed that combining both biomarkers, independent contributions from each (TIMP-1, OR = 2.5, 95% CI: 1.8–3.4, p < 0.0001; CEA < 5 ng/ml, OR = 1.4, 95% CI: 1.1–1.8, and CEA ≥ 5 ng/ml, OR = 2.3, 95% CI: 1.8–3.0 (p < 0.0001)) were obtained. Conclusions. This prospective validation study supports the use of the combination of plasma TIMP-1 and CEA protein measurements as a potential aid in early detection of CRC and specifically of CC.

Coagulation and Fibrinolysis during Laparoscopic Cholecystectomy

Laparoscopic surgery appears to be less traumatic to the patient than open surgery, but its influence upon coagulation and fibrinolysis is incompletely elucidated. Our aim was to measure markers of coagulation and fibrinolysis before, during. and after laparoscopic cholecystectomy (LC). Blood samples drawn on admission, on four occasions during operation as well as 2 hours after operation and on the first postoperative day in 50 patients undergoing elective LC were analyzed for prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), D-dimer (DD), fibrin degradation products (FbDP), tissue-type plasminogen activator (tPA) activity and antigen, and plasminogen activator inhibitor (PAI) activity and antigen. F1+2, SF, DD, and FbDP levels increased significantly after LC. Differences between pre- and postoperative PAI and tPA levels were not significant apart from a transient increase in tPA antigen levels. tPA activity was significantly increased during operation.

Plasma tissue inhibitor of metalloproteinases-1 (TIMP-1): A novel biological marker in the detection of primary colorectal cancer. Protocol outlines of the Danish-Australian endoscopy study group on colorectal cancer detection

Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark, Institute of Veterinary Pathobiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark, Department of Surgical Gastroenterology, St. George Private Hospital, Kogarah, Sydney, Australia, and The Danish Australian Endoscopy Study Group on Colorectal Cancer Detection, and The Danish Colorectal Cancer Cooperative Group, University of Copenhagen, and The Danish Cancer Society, Copenhagen, Denmark

Haemostatic activation in patients with head injury with and without simultaneous multiple trauma.

In a prospective study including 16 patients with multiple trauma and head injury and 14 patients with isolated head injury we measured plasma levels of prothrombin fragment 1 and 2 (F1 + 2) and thrombin/antithrombin III complex (TAT) on admission and on days 1, 2, 3, and 7 after the incident. On admission, all patients had values of F1 + 2 and TAT above the reference range. Admission levels of both F1 + 2 and TAT were significantly higher compared with levels on the following days. Admission levels of F1 + 2 was significantly correlated to the Injury Severity Score. TAT was higher in patients with multiple trauma than in patients with isolated head injury and were significantly correlated to the Injury Severity Score on admission and on day 3. Levels of F1 + 2 were significantly lower on day 1 in four patients with post-traumatic pulmonary dysfunction compared with patients without pulmonary dysfunction. With respect to levels of TAT, no differences were detected between patients with and without pulmonary dysfunction.

Coagulation, inflammatory, and stress responses in a randomized comparison of open and laparoscopic repair of recurrent inguinal hernia

BackgroundIn previous comparisons of inflammatory and stress responses to open (OR) and laparoscopic (LR) hernia repair, all operations were performed under general anesthesia. Since local anesthesia is widely used for OR, a comparison of this approach with LR seemed relevant.MethodsPatients with recurrent inguinal hernia were randomized to OR under local anesthesia (n = 30) or LR under general anesthesia (n = 31). The magnitude of the surgical trauma was assessed by measuring markers of coagulation (prothrombin fragment 1 + 2), endothelial activation (von Willebrand factor), inflammation [leukocytes, interleukin-6, -8 and -10, granulocyte macrophage colony-stimulating factor, and C-reactive protein (CRP)], and endocrine stress (cortisol) in blood collected before operation, 4 h postincision, and on postoperative day 2.ResultsLeukocyte counts and interleukin-6 and CRP levels increased in both groups, with the CRP increase being significantly greater in the OR group. The other markers did not increase significantly.ConclusionThe acute phase response was more pronounced after OR, even when this was done under local anesthesia. Both techniques seemed rather atraumatic.

Adenocarcinoma Arising from the Rectal Stump Eleven Years after Excision of an Ileal J-Pouch in a Patient with Ulcerative Colitis: Report of a Case

Adenocarcinomas in relation to the ileal J-pouch after restorative proctocolectomy for ulcerative colitis have been recently reported with increasing frequency. All previously reported cases have occurred in patients with their ileal pouch in situ. We report a case of adenocarcinoma in the anal canal 11xa0years after removal of a failed ileal J-pouch. Mucosectomy had been performed at the restorative proctocolectomy. The anus had been left in place at the pouch excision because of severe fibrosis in the pelvis. If it is decided to remove an ileal pouch permanently, a total abdominoperineal excision should be performed, particularly in patients with risk factors for cancer development.

Serum YKL-40 in Risk Assessment for Colorectal Cancer: A Prospective Study of 4,496 Subjects at Risk of Colorectal Cancer

The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18–97)] referred to endoscopy due to symptoms or other risk factors for colorectal cancer. Blood samples were collected just before large bowel endoscopy. Serum YKL-40 was determined by ELISA. Serum YKL-40 was higher (P < 0.0001, unadjusted for confounding covariates) in subjects diagnosed with colon cancer (median 126 μg/L, 25%–75%: 80–206 μg/L) and rectal cancer (104, 72–204 μg/L) compared with subjects with adenoma (84, 53–154 μg/L), other nonmalignant findings (79, 49–138 μg/L), and no findings (62, 41–109 μg/L). Serum YKL-40 independently predicted colorectal cancer [OR, 1.53; 95% confidence interval (CI), 1.40–1.67; AUC = 0.68, P < 0.0001]. Restricting the analysis to subjects with no comorbidity increased the OR for serum YKL-40 to predict colorectal cancer (OR, 1.82; 1.58–2.08; AUC = 0.73, P < 0.0001). Combining serum YKL-40 and CEA demonstrated that both were significant [(YKL-40, OR, 1.27; 95% CI, 1.16–1.40); (CEA, OR, 1.92; 1.75–2.10; AUC = 0.75, P < 0.0001; OR for a 2-fold difference in marker level)]. Multivariable analysis (YKL-40, CEA, age, gender, body mass index, and center) showed that serum YKL-40 was a predictor for colorectal cancer in individuals without comorbidity (OR, 1.25; 95% CI, 1.05–1.40; P = 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84–1.14; P = 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful in combination with other biomarkers in risk assessment for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 621–6. ©2015 AACR.

Markers of coagulation and fibrinolysis after fractures of the lower extremities.

The study was performed to detect activation of coagulation and fibrinolysis in terms of prothrombin fragment 1 and 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), and soluble fibrin monomers (FM) in plasma from 39 patients with fractures of the lower extremities. We found substantially elevated levels of the molecular markers at admission and on the day after admission (Day 1) compared with control levels. Admission levels of F1 + 2, TAT, FbDP and FgDP were significantly higher compared with levels on day 1, whereas levels of FM were not significantly different between the two days. Generally there were good correlations between all markers of coagulation and fibrinolysis at admission whereas correlations were weaker or absent on day 1. In conclusion we found substantial haemostatic activation as a immediate response to trauma. Increased levels of F1 + 2, TAT, FM, FbDP and FgDP appear to be a normal physiological reaction after fractures of the lower extremities.

Markers of Coagulation and Fibrinolysis in Portal Blood from Patients with and without Gastric Malignancy

BACKGROUNDnThe origin of coagulation and fibrinolysis abnormalities in cancer patients is unknown. The aim of this study was to measure markers of coagulation and fibrinolysis in portal and peripheral blood from patients with and without gastric malignancy.nnnMETHODSnBlood samples were drawn from the portal vein and a peripheral vein in 39 patients undergoing elective gastric surgery, 18 for gastric malignancy and 21 for benign disorders, and analyzed for prothrombin fragment 1 + 2 (F1 + 2), thrombin-anti-thrombin III complex (TAT), fibrinogen and fibrin degradation products (FgDP, FbDP), and fibrinopeptide A (FpA).nnnRESULTS AND CONCLUSIONSnIn portal blood, levels of F1 + 2, TAT, FpA, FgDP, and FbDP did not differ in the two groups. In peripheral blood, levels of FpA and FbDP were higher in cancer patients, but in a multiple regression model malignancy did not contribute significantly to variation in peripheral FpA or FbDP levels. In both groups FpA levels were higher in portal blood than in peripheral blood.

Re-resection rates and risk characteristics following breast conserving surgery for breast cancer and carcinoma in situ: A single-centre study of 1575 consecutive cases.

OBJECTIVESnTo examine the frequency of re-resections and describe risk characteristics: invasive carcinoma or carcinoma in situ (CIS), palpability of the lesion, and neoadjuvant chemotherapy.nnnRESULTSn1703 breast conserving surgeries were performed: 1575 primary breast conserving surgeries (BCS), and 128 diagnostic excisions (DE). 176 BCS (11.2% [9.6; 12.7]) and 100 DE had inadequate margins indicating re-resection. The overall re-resection rate was 16.2% [14.5; 18.0]. 10.3% of invasive carcinoma BCS patients, and 28.6% CIS patients underwent re-resection (relative risk (RR) 2.8 [1.9; 4.1]). Invasive lobular carcinoma (ilc) had an RR of re-resection of 2.5 [1.7; 3.8], compared with invasive ductal carcinoma (idc).nnnCONCLUSIONnOverall 11.2% of the BCS patients needed a re-resection. For isolated CIS (28.6%), RR of re-resection was almost three times as high compared to invasive carcinoma (10.3%). Ilc had an RR of re-resection of 2.5 compared to idc. Palpability and neoadjuvant chemotherapy did not significantly influence the risk of re-resection.