Acute burn care in resource-limited settings: A cohort study on treatment and outcomes in a rural regional referral hospital in Tanzania.

BACKGROUND: Only a few papers are published on the safety and effectiveness of acute burn care in low-income countries. A cohort study was therefore carried out to determine such outcomes. METHODS: The study was conducted in a rural Tanzanian hospital in 2017-2018. All patients admitted with burns were eligible. Complications were scored during admission as an indication for safety. Survivors of severe burn injuries were evaluated for time of reepithelialization, graft take, disability (WHODAS2.0) and quality of life (EQ5D-3L) up to 3 months post-injury, as an indication of effectiveness. RESULTS: Patients presented on average at 5 days after injury (SD 11, median 1, IQR 0-4). Three patients died at admission. The remaining 79 were included in the cohort. Their median age was 3 years (IQR 2-9, range 0.5-49), mean TBSA burned 12% (SD10%) and mortality rate 11.4%. No surgery-related mortality or life-threatening complications were observed. Skin grafting was performed on 29 patients at a delayed stage (median 23 days, IQR 15-47). Complications of skin grafts included partial (25% of procedures) and complete graft necrosis (8% of procedures). The mean time to reepithelialization was 52 (SD 42) days after admission. Disability and quality of life improved from admission to 3 months after injury (p<0.001, p<0.001, respectively). CONCLUSION: In this resource-limited setting patients presented after a delay and with multiple complications. The mortality during the first two weeks after admission was high. Surgery was found to be safe and effective. A significant improvement in disability and quality of life was observed.

The development of burn scar contractures and impact on joint function, disability and quality of life in low- and middle-income countries: A prospective cohort study with one-year follow-up.

OBJECTIVE: The aim of this study was to assess the development of burn scar contractures and their impact on joint function, disability and quality of life in a low-income country. METHODS: Patients with severe burns were eligible. Passive range of motion (ROM) was assessed using lateral goniometry. To assess the development of contractures, the measured ROM was compared to the normal ROM. To determine joint function, the normal ROM was compared to the functional ROM. In addition, disability and quality of life (QoL) were assessed. Assessments were from admission up to 12 months after injury. RESULTS: Thirty-six patients were enrolled, with a total of 124 affected joints. The follow-up rate was 83%. Limited ROM compared to normal ROM values was observed in 26/104 joints (25%) at 12 months. Limited functional ROM was observed in 55/115 joints (48%) at discharge and decreased to 22/98 joints (22%) at 12 months. Patients who had a contracture at 12 months reported more disability and lower QoL, compared to patients without a contracture (median disability 0.28 versus 0.17 (p = 0.01); QoL median 0.60 versus 0.76 (p = 0.001)). Significant predictors of developing joint contractures were patient delay and the percentage of TBSA deep burns. CONCLUSION: The prevalence of burn scar contractures was high in a low-income country. The joints with burn scar contracture were frequently limited in function. Patients who developed a contracture reported significantly more disability and lower QoL. To limit the development of burn scar contractures, timely access to safe burn care should be improved in low-income countries.

Radiological findings in spontaneous cerebrospinal fluid leaks of the temporal bone.

BACKGROUND AND OBJECTIVE: Spontaneous cerebrospinal fluid leak of the temporal bone is an emerging clinical entity for which prompt and accurate diagnosis is difficult given the subtle signs and symptoms that patients present with. This study sought to describe the key temporal bone abnormalities in patients with spontaneous cerebrospinal fluid leak. METHODS: A retrospective cohort study was conducted of adult patients with biochemically confirmed spontaneous cerebrospinal fluid leak. Demographics and radiological features identified on computed tomography imaging of the temporal bones and/or magnetic resonance imaging were analysed. RESULTS: Sixty-one patients with spontaneous cerebrospinal fluid leak were identified. Fifty-four patients (88.5 per cent) underwent both temporal bone computed tomography and magnetic resonance imaging. Despite imaging revealing bilateral defects in over 75 per cent of the cohort, only two patients presented with bilateral spontaneous cerebrospinal fluid leaks. Anterior tegmen mastoideum defects were most common, with an average size of 2.5 mm (range, 1-10 mm). CONCLUSION: Temporal bone computed tomography is sensitive for the identification of defects when suspicion exists. In the setting of an opacified middle ear and/or mastoid, close examination of the skull base is crucial given that this fluid is potentially cerebrospinal fluid.

Burn scar contracture release surgery effectively improves functional range of motion, disability and quality of life: A pre/post cohort study with long-term follow-up in a Low- and Middle-Income Country.

OBJECTIVE: Burn scar contractures limit range of motion (ROM) of joints and have substantial impact on disability and the quality of life (QoL) of patients, particularly in a Low- and Middle-Income Country (LMIC) setting. Studies on the long-term outcome are lacking globally; this study describes the long-term impact of contracture release surgery performed in an LMIC. METHODS: This is a pre-post cohort study, conducted in a referral hospital in Tanzania. Patients who underwent burn scar contracture release surgery in 2017-2018 were eligible. ROM (goniometry), disability (WHODAS 2.0) and QoL (EQ-5D) were assessed. The ROM data were compared to the ROM that is required to perform activities of daily living without compensation, i.e. functional ROM. Assessments were performed preoperatively and at 1, 3, 6 and 12 months postoperatively. RESULTS: In total, 44 patients underwent surgery on 115 affected joints. At 12 months, the follow-up rate was 86%. The mean preoperative ROM was 37.3% of functional ROM (SD 31.2). This improved up to 108.7% at 12 months postoperatively (SD 42.0, p < 0.001). Disability-free survival improved from 55% preoperatively to 97% at 12 months (p < 0.001) postoperatively. QoL improved from 0.69 preoperatively, to 0.93 (max 1.0) at 12 months postoperatively (p < 0.001). Patients who regained functional ROM in all affected joints reported significantly less disability (p < 0.001) and higher QoL (p < 0.001) compared to patients without functional ROM. CONCLUSIONS: Contracture release surgery performed in an LMIC significantly improved functional ROM, disability and QoL. Results showed that regaining a functional joint is associated with less disability and higher QoL.

A primer in artificial intelligence in cardiovascular medicine.

Driven by recent developments in computational power, algorithms and web-based storage resources, machine learning (ML)-based artificial intelligence (AI) has quickly gained ground as the solution for many technological and societal challenges. AI education has become very popular and is oversubscribed at Dutch universities. Major investments were made in 2018 to develop and build the first AI-driven hospitals to improve patient care and reduce healthcare costs. AI has the potential to greatly enhance traditional statistical analyses in many domains and has been demonstrated to allow the discovery of 'hidden' information in highly complex datasets. As such, AI can also be of significant value in the diagnosis and treatment of cardiovascular disease, and the first applications of AI in the cardiovascular field are promising. However, many professionals in the cardiovascular field involved in patient care, education or science are unaware of the basics behind AI and the existing and expected applications in their field. In this review, we aim to introduce the broad cardiovascular community to the basics of modern ML-based AI and explain several of the commonly used algorithms. We also summarise their initial and future applications relevant to the cardiovascular field.

[A fixed drug eruption caused by paracetamol]. / Een 'fixed drug reaction' bij gebruik van paracetamol.

BACKGROUND: Fixed drug eruption is a hypersensitive skin response to drugs, which can present itself in different ways. The skin lesions are usually solitary, but can also appear as a maculopapular rash, Stevens-Johnson syndrome or toxic epidermal necrolysis. While fixed drug eruptions can be caused by various drugs, paracetamol is responsible in 1.5% of cases. CASE DESCRIPTION: A 58-year-old man was seen in general practice with a five-year-old exanthema on his torso, arms and legs. A biopsy from one of the lesions revealed a fixed drug eruption. When asked, the patient admitted using paracetamol for the last five years on a near-daily basis to ease headaches. After cessation of paracetamol, the exanthema gradually disappeared. CONCLUSION: It continues to be important to ask patients with a rash of unclear origin about the use of any medicines. Particularly over-the-counter drugs with relatively few side-effects, such as paracetamol, should be considered.

Vascular replacement using a layered elastin-collagen vascular graft in a porcine model: one week patency versus one month occlusion.

A persistent clinical demand exists for a suitable arterial prosthesis. In this study, a vascular conduit mimicking the native 3-layered artery, and constructed from the extracellular matrix proteins type I collagen and elastin, was evaluated for its performance as a blood vessel equivalent. A tubular 3-layered graft (elastin-collagen-collagen) was prepared using highly purified type I collagen fibrils and elastin fibers, resembling the 3-layered native blood vessel architecture. The vascular graft was crosslinked and heparinised (37 ± 4 µg heparin/mg graft), and evaluated as a vascular graft using a porcine bilateral iliac artery model. An intra-animal comparison with clinically-used heparinised ePTFE (Propaten®) was made. Analyses included biochemical characterization, duplex scanning, (immuno)histochemistry and scanning electron microscopy. The tubular graft was easy to handle with adequate suturability. Implantation resulted in pulsating grafts without leakage. One week after implantation, both ePTFE and the natural acellular graft had 100% patencies on duplex scanning. Grafts were partially endothelialised (Von Willebrand-positive endothelium with a laminin-positive basal membrane layer). After one month, layered thrombi were found in the natural (4/4) and ePTFE graft (1/4), resulting in occlusion which in case of the natural graft is likely due to the porosity of the inner elastin layer. In vivo application of a molecularly-defined tubular graft, based on nature's matrix proteins, for vascular surgery is feasible.

Prevention of postsurgical adhesions using an ultrapure alginate-based gel.

BACKGROUND: Postoperative adhesion formation is a common consequence of abdominal surgery, and constitutes a major source of morbidity and mortality. This study evaluated an ultrapure alginate-based antiadhesive barrier gel. METHODS: Experiments were performed in a rat model with caecal abrasion and peritoneal side wall excision. The primary endpoint was the incidence of adhesions at 14 days after surgery. In experiment 1 (24 rats), animals treated with alginate gel were compared with controls that had no antiadhesive barrier. In experiment 2 (42 rats), alginate gel was compared with sodium hyaluronate carboxymethyl cellulose (HA/CMC) membrane and with no antiadhesive barrier. To check for any remote action of the gel, in experiment 3 (45 rats) application of alginate gel to the ipsilateral versus contralateral side of injury was compared with no antiadhesive barrier. RESULTS: In experiment 1, ultrapure alginate gel reduced the incidence of adhesions from eight of 12 in control animals to one in 12 (P = 0·009). Tissue healing assessed by histology was similar in both groups. In experiment 2, ultrapure alginate gel and HA/CMC membrane showed similar antiadhesive effectiveness, reducing the incidence of adhesions from ten of 14 rats in the control group to three of 14 (P = 0·021) and two of 14 (P = 0·006) respectively. In experiment 3, ultrapure alginate gel reduced the incidence of adhesions at the site of direct application (1 of 15) compared with controls (13 of 15; P = 0·001), but not if applied remotely (9 of 15; P = 0·214). CONCLUSION: Ultrapure alginate gel decreased the incidence of postoperative adhesion formation in this rat model.

Diclofenac causes more leakage than naproxen in anastomoses in the small intestine of the rat.

BACKGROUND: Non-steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated. METHODS: In 104 male Wistar rats, an anastomosis was constructed in both colon and ileum. The rats were divided into groups who received diclofenac (4 mg kg(-1) day(-1)) or naproxen (10 mg kg(-1) day(-1)) daily from the day of surgery or from day 3 after surgery. Animals were killed on day 3 or 7 and analysed for signs of anastomotic dehiscence and wound strength of anastomoses and abdominal fascia. RESULTS: Anastomotic leakage in the ileum (p < 0.0001) and mortality rates (p = 0.001) were significantly increased in the diclofenac group. On day 7, the anastomotic bursting pressure in the ileum remained below that of the controls in the diclofenac- and naproxen-treated rats. When administration of diclofenac was postponed to day 3 after surgery, anastomotic dehiscence was almost absent. The colonic anastomosis and abdominal wall always remained unaffected. CONCLUSIONS: This study implies that immediate postoperative administration of diclofenac and, to a far lesser extent, naproxen can affect healing in the ileal anastomosis in the rat. This negative effect can be prevented by a short postoperative delay in administration. On steroid anti-inflammatory drugs such as the cyclooxygenase isoenzyme inhibitors diclofenac and naproxen are increasingly used for perioperative pain relief, while their potential effects on wound healing are scarcely investigated.

Perioperative pain relief by a COX-2 inhibitor affects ileal repair and provides a model for anastomotic leakage in the intestine.

The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or buprenorphine (0.02 mg/kg subcutaneously every 12 hours). In another 20 rats an anastomosis was constructed in either ileum or colon, and all received carprofen (experiment 2). Animals were sacrificed after 3 days. In experiment 1, the ileal dehiscence rate was 60% in the carprofen group and 0% in the buprenorphine group (P = .0108). Colonic anastomoses in both groups remained patent. In experiment 2, the anastomotic leakage rate was 80% in ileum and 0% in colon. Thus, COX-2 inhibitors can severely interfere with intestinal healing, particularly in the ileum. Perioperative administration of carprofen yields a unique model for anastomotic leakage, which allows translational research on the effectiveness of perisuture line reinforcement.

Hybrid 18F-FDG PET/CT of colonic anastomosis. A possibility to detect anastomotic leakage?

UNLABELLED: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a known method to diagnose inflammatory processes and thus may be a promising imaging technique to detect anastomotic bowel leak. The aim of this study was to assess postoperative FDG uptake in colorectal anastomosis in patients without suspicion of active infection or anastomotic leakage. PATIENTS, METHODS: Design of a prospective observational pilot study in order to assess normal FDG uptake in the patient anastomosis after colorectal surgery. Patients that underwent colorectal surgery with primary anastomosis received FDG-PET of the abdomen, 2-6 days postoperatively. RESULTS: 35 patients met the inclusion criteria. Three patients were not scanned for various reasons. Of the remaining 32 patients, one demonstrated an increased uptake of FDG at the site of the anastomosis. In the other 31 patients FDG uptake was negligible (n = 17) or scored as physiological (n = 14). None of the scanned patients developed a clinical relevant anastomotic leakage within the first 30 days after surgery. CONCLUSION: The present study shows that FDG uptake in colorectal anastomosis remains low within the first six days after surgery in patients without anastomotic leakage. Therefore, FDG-PET might be useful to investigate further as a tool to detect anastomotic leakage in an the early postoperative phase.

BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats.

Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphogenetic proteins (BMPs). To investigate the influence of estrogen deficiency as well as the effect of early intervention, forty female wistar rats underwent ovarectomy (OVX) followed by low calcium diet. Ten rats underwent sham operations, followed by normal diet. After 6 weeks, a closed midshaft femoral fracture was induced. Ten animals received a systemic bisphosphonate injection, 10 injection of BMP-7 in the fracture, and 10 a combination. All then received a normal diet. After 2 weeks healing was evaluated using radiographs, CT, biomechanical testing, and histology. Radiography showed significant increase of bridging in groups treated with BMP-7. Callus volume was higher in these groups. Bending stiffness and strength were similar between OVX and sham, and not influenced by bisphosphonates. Significant increase was seen in groups treated with BMP-7. Histology was in accordance with other endpoints. Early fracture healing was not affected by estrogen deficiency. While no beneficiary effect of bisphosphonate treatment was found, injection of BMP-7 stimulated healing in ovarectomized rats.

Adjuvant radioimmunotherapy after radiofrequency ablation of colorectal liver metastases in an experimental model.

PURPOSE: Radiofrequency ablation (RFA) has shown to improve survival in patients not eligible for surgical resection of colorectal liver metastases. However, recurrences after RFA are a major problem. Adjuvant radioimmunotherapy (RIT) after surgical resection of liver metastases has shown to improve survival. The aim of the present study was to test the hypothesis that adjuvant RIT might be an effective way to prevent recurrent liver metastases after RFA in an experimental model. METHODS: Tumours in the liver were induced by intrahepatic injection of 300,000 CC531 cells in male Wag/Rij rats (n = 60). Ten days later, the intrahepatic tumours were treated with RFA. Adjuvant RIT ((177)Lu-labelled monoclonal antibody MG1 at 300 MBq/kg) was administered intravenously either at the day of RFA (day 10) or 7 days later. Control rats received no treatment. Primary endpoint was survival. RESULTS: Administration of (177)Lu-MG1 resulted in a transient decrease in body weight, compared to no adjuvant treatment. However, no other signs of clinical discomfort were registered. Log rank test showed that the survival curves of the groups treated with RIT, either at day 10 or day 17, did not differ significantly from the survival curve of the rats that did not receive adjuvant treatment (P = 0.902). CONCLUSION: This study shows that adjuvant RIT does not increase survival after RFA of colorectal liver metastases in rats.

Experimental study of radioimmunotherapy versus chemotherapy for colorectal cancer.

BACKGROUND: Radioimmunotherapy (RIT) has been shown to reduce the incidence of local recurrence of colorectal cancer in an experimental model. The aim of the present study was to investigate the survival benefit of RIT compared with chemotherapy. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of CC531 tumour cells. The therapeutic efficacy of (177) Lu-labelled MG1 (single intravenous dose of 300 MBq/kg, n = 20) was compared with that of 5-fluorouracil-based chemotherapy (6 weekly cycles administered intraperitoneally, n = 20) and no treatment (n = 20). The primary endpoint was survival. Toxicity was monitored by bodyweight measurement. RESULTS: Both chemotherapy and RIT affected bodyweight, but the weight of animals in the RIT group remained significantly higher than in the chemotherapy group (median slope of bodyweight plot 0·48 versus 0·30 g/day; P < 0·001). Kaplan-Meier analysis showed that overall survival in the RIT and chemotherapy groups was significantly better than that in the control group (50 and 46 per cent versus 25 per cent respectively after 170 days; P = 0·024 and P = 0·029). Survival after treatment with RIT did not differ from that after chemotherapy (P = 0·911). CONCLUSION: RIT is as effective as chemotherapy in experimental colorectal cancer.

Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model.

BACKGROUND: The combination of cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the treatment of choice for selected patients with peritoneal carcinomatosis (PC) of colorectal origin. However, it remains to be proven whether the addition of HIPEC to CS is essential for the reported survival benefit. METHODS: Sixty WAG/Rij rats were inoculated intraperitoneally with the rat colonic carcinoma cell line CC-531. Animals were randomized into three treatment groups: CS alone, CS followed by HIPEC (mitomycin 15 mg/m(2) ) and CS followed by HIPEC (mitomycin 35 mg/m(2) ). Survival was the primary outcome parameter. RESULTS: The median survival of rats treated with CS alone was 43 days. Rats receiving HIPEC 15 mg/m(2) and HIPEC 35 mg/m(2) both had a significantly longer median survival of 75 days (P = 0·003) and 97 days (P < 0·001) respectively. Rats receiving HIPEC showed a significantly lower tumour load at autopsy compared with rats treated with CS alone. CONCLUSION: A combination of CS and HIPEC results in longer survival than CS alone in rats with PC of colorectal origin.

Neoadjuvant radiochemotherapy increases matrix metalloproteinase activity in healthy tissue in esophageal cancer patients.

BACKGROUND: Neoadjuvant radiochemotherapy (RCT) is thought to result in a favorable oncological outcome in esophageal cancer patients. Unfortunately, it also implies that adjacent healthy tissue is preoperatively exposed to the potential damaging influence of RCT. Here, the impact of preoperative RCT on matrix metalloproteinase (MMP) expression in healthy esophageal tissue aligned with the tumor at the time of surgery is examined. PATIENTS AND METHODS: 23 patients participating in a clinical trial were randomized to either the control (n = 12) or the neoadjuvant RCT group (n = 11). In the latter group, surgery was performed 5 weeks after the last course of RCT. Full-thickness biopsies were taken from healthy esophageal tissue at the proximal border of the resection specimen and more distally next to the tumor. MMP-2 and MMP-9 activity in the samples was assessed by quantitative gelatin zymography and immunohistochemistry. RESULTS: In the proximal segment, the activities of the MMP-9-dimer (135 kDa) and proMMP-9 (92 kDa) were significantly increased in the RCT group as compared with the control group: 28.5 versus 3.0 (p = 0.025) and 87.7 versus 13.0 (p = 0.015) arbitrary units for 135 kDa and 92 kDa, respectively. In the distal part, RCT resulted in a significant increase of proMMP-2 (72 kDa: 35.8 versus 17.8, p = 0.005) and proMMP-9 (81.2 versus 23.3, p = 0.03). CONCLUSION: In esophageal cancer patients, neoadjuvant RCT results in increased MMP expression in healthy esophageal tissue as measured at the time of surgery. Since increased levels of MMPs are associated with severe postoperative complications including anastomotic leakage this finding necessitates further clinical research.

Radioimmunotherapy prevents local recurrence of colonic cancer in an experimental model.

BACKGROUND: Radioimmunotherapy (RIT) is suitable for the treatment of microscopic residual disease and might therefore have an adjuvant role after colonic cancer surgery. METHODS: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of 2 x 10(6) CC531 tumour cells. The biodistribution of (111)In-labelled MG1 monoclonal antibody was assessed after intraperitoneal administration. The therapeutic efficacy of (177)Lu-labelled MG1 (74 MBq per rat), administered on the day of surgery (D0, n = 13) or 5 days later (D5, n = 13), was compared with that of carrier only (n = 13). The primary endpoint was perianastomotic tumour growth 28 days after surgery. RESULTS: (111)In-labelled MG1 preferentially accumulated in perianastomotic CC531 tumours. RIT resulted in a transient reduction in bodyweight in both treatment groups compared with controls, but there were no other signs of clinical discomfort. No macroscopic or microscopic perianastomotic tumour growth was found in eight of 11 animals in the D0 group and 11 of 13 in the D5 group, whereas 11 of 13 controls had macroscopic tumour (P = 0.011 and P = 0.001 respectively). CONCLUSION: This study suggests that RIT may be an effective adjuvant treatment for preventing local recurrence after resection of colonic cancer.

Early anastomotic repair in the rat intestine is affected by transient preoperative mesenteric ischemia.

INTRODUCTION: During bowel surgery, perioperative blood loss and hypotension can lead to transient intestinal ischemia. Recent preclinical studies reveal that the strength of intestinal anastomoses can be compromised after reperfusion. So far, this phenomenon has not been investigated in the very first days of healing when wound strength is lowest. MATERIAL AND METHOD: Ischemia was induced in rats by clamping both the superior mesenteric artery and ileal branches for 30 min. Immediately after declamping, anastomoses were constructed in both terminal ileum and descending colon. The same was done in control groups after sham-ischemia. Anastomotic bursting pressure and breaking strength were measured immediately after operation (day 0) and after 1, 2, or 3 days. Anastomotic hydroxyproline content, gelatinase activity, and histology were analyzed. RESULTS AND DISCUSSION: In ileal anastomoses, at day 1, both the breaking strength and bursting pressure were significantly (p < 0.05) lower in the ischemic group, while at day 2, this was the case for the bursting pressure only. In the colon, the bursting pressure in the ischemic group was lower at day 1. Anastomotic hydroxyproline content remained unchanged. Increased presence of the various gelatinase activities was found in ileum only at day 0 and in colon at days 1 and 2. Histological mucosal damage was found in ischemia-reperfusion groups. CONCLUSION: Transient mesenteric ischemia can negatively affect anastomotic strength during the very first days of healing, even if the tissue used for anastomotic construction looks vital.

The effects of adjuvant experimental radioimmunotherapy and hyperthermic intraperitoneal chemotherapy on intestinal and abdominal healing after cytoreductive surgery for peritoneal carcinomatosis in the rat.

BACKGROUND: Cytoreductive surgery (CS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) results in limited survival benefit and high morbidity and mortality rates in patients with peritoneal carcinomatosis (PC). Radioimmunotherapy (RIT) after CS of experimental PC has been shown to increase survival and compare favorably to HIPEC. The effects of RIT and HIPEC on wound healing after CS need to be determined. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to CS and anastomotic construction only or followed by RIT or HIPEC. RIT consisted of 74 MBq (177)lutetium-labeled anti-CC531 antibody MG1. HIPEC was performed by a closed abdominal perfusion technique using mitomycin-C during 60 minutes. Anastomotic and abdominal wall strength measurements were performed 3 and 5 days after surgery. RESULTS: At day 5, bursting pressure in ileum and colon anastomoses in the CS + HIPEC group, but not in the CS + RIT group, was lower (P < .01) than in the CS group. In the CS group, the colonic bursting site was more often outside the true anastomotic area (8 of 12 animals) than in the CS + HIPEC (1 of 12) and CS + RIT (5 of 12) groups. Abdominal wall strength in the CS + HIPEC group was significantly (P < .01) lower, at both measuring points, than that in both the CS group and the CS + RIT group. There was no difference between the latter. CONCLUSION: As adjuvant to CS, HIPEC showed a decrease in anastomotic and abdominal wall wound strength in a model of PC of CRC, whereas RIT did not.

Plasminogen activator, but not systemic antibiotic therapy, prevents abscess formation in an experimental model of secondary peritonitis.

BACKGROUND: Intra-abdominal abscesses are sources of recurrent or ongoing abdominal sepsis. They are an important target for prevention and treatment during or after surgical treatment of peritonitis. Experimental data suggest that fibrinolytic therapy may be effective when antibiotics are not. METHODS: Peritonitis was induced via intra-abdominal injection of a faeces and bacteria mixture in male Wistar rats. Surgical debridement was performed after 1 h. Next to untreated controls, animals were treated with antibiotics (ceftriaxone plus metronidazole), recombinant tissue plasminogen activator (rtPA) or both. Abdominal fluid samples were taken at 24, 72 and 120 h for interleukin 6, interleukin 10 and tumour necrosis factor alpha measurements and cell counts. After 5 days the abdomen was inspected for the presence of abscesses. RESULTS: Antibiotics did not significantly affect abscess formation. However, giving rtPA significantly reduced the number of rats with abscesses and the abscess load per rat, both in the absence and presence of concomitant antibiotic therapy. No adverse side-effects were observed and no meaningful differences in the local inflammatory response were found. CONCLUSION: In this rat model, rtPA consistently reduced abscess formation after surgical treatment of secondary peritonitis. It therefore represents a promising adjuvant to conventional therapy.