Detection of early anastomotic leakage by intraperitoneal microdialysis after low anterior resection for rectal cancer: a prospective cohort study.

AIM: Anastomotic leakage (AL) is a common and serious complication following sphincter-preserving surgery for rectal cancer. Early detection and intervention can improve clinical outcomes. The aim of this prospective cohort study was to compare intraperitoneal microdialysis with a clinical scoring system for early detection of AL. METHOD: A microdialysis catheter was anchored near the anastomosis at low anterior resection (LAR) for rectal cancer. Peritoneal fluid samples were analysed (lactate, pyruvate, glucose and glycerol concentration) 4-hourly and compared with a daily clinical leak score (DULK = Dutch leakage). At day 7 a pelvic CT with rectal contrast enema was performed to establish if there had been a radiological leak. RESULTS: In this two-centre study, 129 patients [median age 65 (26-82) years; 60.5% male] underwent LAR. The leak rate was 27% (grade A, n = 11; grade B, n = 12; grade C, n = 12). Receiver operator characteristic analysis demonstrated a lactate cut-off value of 9.8 mm and had 77% sensitivity, 82% specificity, 78% accuracy, a positive predictive value (PPV) of 58, a negative predictive value (NPV) of 88 (CI 79-94) and an area under the curve (AUC) of 0.9 for AL. This compared with a clinical score ≥ 4, which had 57% sensitivity, 79% specificity, 71% accuracy, a PPV of 46, a NPV of 82 and an AUC of 0.7 for AL. The mean day for a positive test when using delta lactate ≥ 6.3 mm was 1.6 days and for leak score ≥ 4 it was 3.3 days (NS). CONCLUSION: When AL occurs, intraperitoneal lactate concentration increases over time, and at a certain cut-off has a higher sensitivity, specificity, accuracy, PPV and NPV than a clinical scoring system.

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.

OBJECTIVES: To examine the frequency of re-resections and describe risk characteristics: invasive carcinoma or carcinoma in situ (CIS), palpability of the lesion, and neoadjuvant chemotherapy. RESULTS: 1703 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). CONCLUSION: Overall 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.

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

BACKGROUND: In 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. METHODS: Patients 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. RESULTS: Leukocyte 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. CONCLUSION: The acute phase response was more pronounced after OR, even when this was done under local anesthesia. Both techniques seemed rather atraumatic.

Randomized study of coagulation and fibrinolysis during and after gasless and conventional laparoscopic cholecystectomy.

BACKGROUND: Carbon dioxide pneumoperitoneum may be an important pathophysiological factor stimulating the coagulation system during conventional laparoscopic cholecystectomy. The aim of this study was to test the hypothesis that gasless laparoscopy produces smaller changes in the coagulation and fibrinolytic system than carbon dioxide pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. METHODS: Fifty patients were allocated randomly to conventional (n = 26) or gasless (n = 24) laparoscopic cholecystectomy. Blood samples were obtained on admission, after induction of anaesthesia, after insufflation or traction, 30 min after introduction of the laparoscope, 10 min after exsufflation of carbon dioxide or traction, 4 h after extubation and 24 h after operation. RESULTS: The two groups were comparable with respect to age, sex, body mass index and duration of operation. Plasma levels of prothrombin fragment 1 and 2 (F1 + 2), soluble fibrin and D-dimer did not differ between the two groups. F1 + 2 levels varied significantly in both groups during and after operation (P < 0.001). Soluble fibrin and D-dimer levels did not change during operation in either group, but after operation the levels increased significantly in both groups (P < 0.001). CONCLUSION: Carbon dioxide pneumoperitoneum does not enhance the activation of coagulation and fibrinolysis associated with laparoscopic cholecystectomy. The coagulation and fibrinolytic systems are activated during and after gasless as well as conventional laparoscopic cholecystectomy.

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.

Determination of coagulation inhibitor levels and resistance to activated protein C in patients undergoing gastric surgery for benign and malignant disorders.

The aim of the present study was to determine plasma levels of protein C antigen (PC:Ag) and activity (PC:Act), tissue factor pathway inhibitor (TFPI), protein S (PS), antithrombin (AT), heparin cofactor II (HCII), and resistance to activated protein C (APCR) before, during and after elective gastric surgery in order to compare patients with and without gastric malignancy. Blood was collected from a forearm vein of two age-matched patient groups undergoing elective gastric surgery, 9 patients with and 9 patients without gastric malignancy. The plasma levels of the parameters were determined preoperatively, intraoperatively, and on days 1 and 7 postoperatively. On the 1st and 7th postoperative day, plasma levels of HCII were significantly lower in patients operated for gastric malignancy than in those operated for benign disorders, but levels of TFPI, PC:Act, PC:Ag, AT, PS and APCR did not differ in the postoperative period. The day-to-day variation was also rather similar in the two patient groups.

Markers of haemostatic activation before and after blood donation and plasmapheresis.

BACKGROUND AND OBJECTIVES: Previous studies have reported signs of haemostatic activation after haemorrhage. The aim of this study was to measure sensitive markers for haemostatic activation after blood donation or plasmapheresis in healthy donors. MATERIALS AND METHODS: Blood samples were drawn before as well as 5 min and 1 h after donation in 40 male donors, of whom 29 gave 1 unit of blood and 11 underwent plasmapheresis. Standard assays were used. RESULTS: Plasma concentrations of the activation markers prothrombin fragment 1 + 2, thrombin-antithrombin complexes, and von Willebrand factor did not increase after blood or plasma donation. CONCLUSIONS: In our opinion, these procedures are safe.

Poor correlation between soluble fibrin concentrations measured by two commercially available immunoassays.

Soluble fibrin (SF) has attracted considerable interest as a marker for haemostatic activation. Two new enzyme immunoassays for SF, Enzymun-Test FM (Boehringer Mannheim, Germany) and Fibrinostika Soluble Fibrin (Organon Teknika, Belgium) have recently become commercially available. We measured plasma levels of SF in clinically obtained blood samples in order to compare the two new assays. Blood was drawn from 10 healthy volunteers and from 149 patients on the first day after surgery for fractures of the upper part of the femur. Collection and processing was done according to the manufacturers' recommendations. In the patients, levels found by the two assays were significantly different. The Enzymun-Test assay reported a median (range) of 11.87 (2.66 - > 62.20) mg/l, whereas the Fibrinostika assay found a median (range) of 3.34 (1.08 - >10) mg/l. The correlation coefficient was 0.38 (Spearman). A poor correlation was thus found between values obtained by the two assays in the patient category chosen. Further validation of the assays is necessary.

Plasminogen activators and plasminogen activator inhibitor in portal blood from patients with and without gastric malignancy.

BACKGROUND: Plasminogen activators (PA) may be released by the gut and eliminated by the liver. Patients with liver disorders or malignancy often have abnormal plasma levels of PAs. Some tumours may produce PAs. METHODS: In patients undergoing gastric surgery for malignant (n = 18) or benign (n = 21) disorders., blood drawn from the portal vein and a peripheral vein was analysed for tissue-type plasminogen activator antigen and activity (tPA: Ag, tPA: Act), single-chain urokinase-type plasminogen activator activity (scuPA: Act), and plasminogen activator inhibitor antigen and activity (PAI: Ag, PAI: Act). RESULTS AND CONCLUSIONS: In both groups tPA: Act and scuPA: Act levels were significantly higher in portal blood than in peripheral blood, but tPA: Ag and PAI: Act levels did not differ. PAI: Act levels were significantly lower in patients with malignant disease, but levels of the other markers did not differ in the two groups.

Plasminogen activators and plasminogen activator inhibitor before and after surgery in patients with and without gastric malignancy.

Pre- and postoperative plasma levels of tissue-type plasminogen activator (t-PA), single-chain urinary plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) were measured in 40 patients undergoing gastric surgery in order to compare patients operated for benign (n = 21) and malignant (n = 19) disease. On the 1st postoperative day, the PAI-1 activity was significantly increased and the t-PA activity significantly decreased in the malignant group, whereas only insignificant changes were seen in the benign group. In contrast, the t-PA activity was significantly increased 1 week after surgery in patients without malignancy. In both groups, the single-chain urinary plasminogen activator activity decreased on the 1st postoperative day, but was significantly increased 1 month after operation. Thus, the two groups reacted differently, but it remains to be determined whether this bears any relationship to the well-known high risk of postoperative venous thromboembolism in cancer patients.

Haemostatic activation before and after surgery in patients with and without gastric malignancy.

Pre- and postoperative plasma levels of Prothrombin Fragment 1 + 2 (F1 + 2), Thrombin-antithrombin III complex (TAT), Fibrinopeptide A (FpA), Fibrin and Fibrinogen Degradation Products (FbDP, FgDP) and Soluble Fibrin (SF) were measured in 40 patients undergoing gastric surgery in order to compare patients operated for benign (n = 21) and malignant (n = 19) disease. Plasma levels of F1 + 2, TAT, FbDP and SF on the first postoperative day were significantly higher than before operation. F1 + 2 and FbDP levels were further increased one week after surgery, at which time FgDP levels were also higher than preoperatively. A significant postoperative increase in FpA levels was found only in patients with malignant disease. When age was taken into consideration, significant differences between patients with and without malignancy were found only in the late postoperative period, as cancer patients had higher FpA and FbDP levels one week after surgery and higher FbDP levels one month after discharge from hospital.

Markers of coagulation and fibrinolysis in portal blood from patients with and without gastric malignancy.

BACKGROUND: The 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. METHODS: Blood 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). RESULTS AND CONCLUSIONS: In 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.

Markers of coagulation and fibrinolysis in blood drawn into citrate with and without D-Phe-Pro-Arg-Chloromethylketone (PPACK).

In order to compare levels of Prothrombin Fragment 1 + 2 (F1 + 2), Thrombin-antithrombin III complex (TAT), Fibrinogen Degradation Products (FgDP) and Fibrin Degradation Products (FbDP) in plasma from blood drawn into sodium citrate with and without the protease inhibitor D-Phe-Pro-Arg-Chloromethylketone (PPACK), blood samples were collected from 41 patients on the first day after elective gastric surgery. Levels of F1 + 2, TAT and FbDP were not significantly different in plasma with and without PPACK. FgDP levels were significantly higher in plasma with PPACK. Our results did not support previous suggestions that PPACK should be used as a routine anticoagulant for measurement of haemostatic activation products.

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.

[Low molecular heparin in prevention of thrombosis in orthopedic surgery]. / Tromboseprofylakse med lavmolekylaert heparin i ortopaedkirurgien.

The review encompasses all published clinical studies of prophylactic treatment with low molecular weight (LMW) heparins marketed in Denmark when used to prevent thrombosis in patients undergoing elective or emergency orthopaedic operations. In elective hip surgery, LMW-heparin was more effective than placebo in reducing the incidence of deep vein thrombosis. There was significantly better anti-thrombotic effect of LMW-heparin, given in recommended doses, than of Dextran 70. When compared to low-dose heparin, the incidence of deep vein thrombosis was lowest using LMW-heparin, but only one study found the difference significant. LMW-heparin compared to low-dose heparin in combination with dihydroergotamine showed no significant difference with respect to either effect of safety. The use of LMW-heparin as prophylactic treatment for patients with either trochanteric or femoral neck fractures is as yet not nearly so well-documented. The relatively few studies that have been carried out show large variation between the different LMW-heparins. There is need for a study comparing the effect of LMW-heparin with that of low-dose heparin in these patients, both with respect to thrombosis prevention and influence on total mortality.

Fibrinogen and fibrin derivatives in traumatized patients: relation to injury severity and posttraumatic pulmonary dysfunction.

In a prospective study including 30 traumatized patients, levels of fibrinogen, fibrinopeptide A (FpA), fibrin monomers (FM) and fibrin degradation products (FbDP) were measured on admission and on days 1, 2, 3 and 7 after the incident. High levels of FpA, FM and FbDP were observed immediately after the trauma. Fibrinogen levels increased during the first 7 posttraumatic days whereas FpA and FM decreased. FbDP was significantly higher on day 7 than on day 3. All variables were to some extent correlated to the injury severity score. FbDP were significantly lower on the day after admission in 4 patients who developed pulmonary dysfunction compared with patients without this complication.

[Intrathoracic perforation of stomach ulcer in a massive hiatal hernia]. / Intratorakal perforation af ventrikelulcus i et stort hiatushernie.

A case of intrathoracic perforation of a chronic gastric ulcer in a hiatus hernia is presented. A 67-year-old woman had suffered from interscapular pain and epigastric discomfort following large meals for four years. During the week before admission, the epigastric and interscapular pain increased, reaching a crescendo in the 24 hours before the patient's arrival in the emergency room. Chest and abdominal x-ray showed free gas and a large hiatus hernia with an intrathoracic stomach. At laparotomy, the stomach was gently returned to the abdominal cavity, and a perforated chronic gastric ulcer was found on the greater curvature. The ulcer was excised, and the diaphragmatic crura were approximated. Apart from wound dehiscence, the postoperative course was uneventful.

Venous thromboembolism and cancer.

The literature was reviewed in an attempt to determine whether patients with cancer have an increased risk of venous thromboembolism, i.e. deep vein thrombosis and pulmonary embolism. From case reports it was apparent that various thromboembolic or thrombophlebitic manifestations may be found in a small number of patients, although it is possible that not all cases belong to the same clinical or pathogenetic entity. In clinical series it was found that the risk of postoperative venous thromboembolism was increased in cancer patients, but the possibility that this was due to associated risk factors, rather than to the mere presence of a tumour, could not be excluded. Little is known about patients not undergoing surgery. Retrospective postmortem studies have found more thrombi in patients with malignancy, but a prospective study failed to demonstrate an association between malignancy and pulmonary embolism. It is possible that different types of cancer show various degrees of association with venous thromboembolism. We conclude that further studies should be performed to provide a firm clinical and pathoanatomical basis for investigations into the pathogenesis of venous thromboembolism.

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.