Upadacitinib tartrate in rheumatoid arthritis.

In rheumatoid arthritis (RA) there is an unmet therapeutic need, as a substantial proportion of patients does not achieve low disease activity or remission despite the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs). The Janus kinase (JAK) inhibitors are the most recently added drug category in the therapeutic armamentarium in RA. Upadacitinib tartrate (Rinvoq), a selective and reversible JAK1 inhibitor, inhibited interleukin (IL)-6 and IL-7 and ameliorated adjuvant-induced arthritis in preclinical studies. In phase III randomized controlled trials (RCTs), upadacitinib, as monotherapy or in combination with csDMARDs, showed efficacy in RA patients with inadequate response to csDMARDs or bDMARDs. In a head-to-head RCT, upadacitinib 15 mg once daily was superior to adalimumab in achieving remission and in patient-reported outcomes. Upadacitinib has a good safety profile but it may increase the risk for herpes zoster, and as a substrate of cytochrome P450 (CYP) enzyme CYP3A4 it should not be coadministered with strong CYP3A4 inducers. Upadacitinib is contraindicated in patients with active tuberculosis, serious infections, active malignancy and in patients with severe liver impairment. Upadacitinib has been approved for the treatment of moderate to severe RA.

Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort.

BACKGROUND: European data indicate that systemic sclerosis (SSc)-related death rates are increasing, thus raising concerns about SSc's optimal management. Herein, we describe current treatment modalities and drug survival in a real-life SSc cohort. METHODS: Details on immunosuppressive/antiproliferative (methotrexate, mycophenolate, cyclophosphamide, azathioprine, rituximab, tocilizumab) and vasoactive agent [(endothelin receptor antagonists (ERAs), sildenafil, iloprost, and calcium channel blockers (CCB)] administration during the disease course (11.8 ± 8.4 years, mean + SD) of 497 consecutive patients examined between 2016 and 2018 were retrospectively recorded. Drug survival was assessed by Kaplan-Meier analysis. RESULTS: Methotrexate was the most frequently administered immunosuppressive/antiproliferative agent (53% of patients), followed by cyclophosphamide (26%), mycophenolate (12%), and azathioprine (11%). Regarding vasoactive agents, CCB had been ever administered in 68%, ERAs in 38%, iloprost in 7%, and sildenafil in 7% of patients; 23% of patients with pulmonary fibrosis had never received immunosuppressive/antiproliferative agents, 33% of those with digital ulcers had never received ERAs, iloprost, or sildenafil, whereas 19% of all patients had never received either immunosuppressive/antiproliferative or other than CCB vasoactive agents. Survival rates of methotrexate, cyclophosphamide, and mycophenolate differed significantly, being 84/75%, 59/43%, and 74/63% at 12/24 months, respectively, with inefficacy being the most frequent discontinuation cause. Conversely, CCB, ERAs, and sildenafil had high and comparable retention rates of 97/91%, 88/86%, and 80/80%, respectively. CONCLUSIONS: Existing therapeutic limitations indicate that more evidence-based treatment is warranted for successful management of SSc. Vasculopathy seems to be managed more rigorously, but the low retention rates of immunosuppressive/antiproliferative drugs suggest that effective and targeted disease-modifying agents are warranted.

Anti-C1q autoantibodies are frequently detected in patients with systemic sclerosis associated with pulmonary fibrosis.

BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE), but their presence in other rheumatic diseases has not been adequately investigated. OBJECTIVES: We aimed to assess anti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc). METHODS: In total 124 patients with SSc were studied; 106 were female and the median age was 59·4 years (range 25-81·4). Overall 75 (60·5%) had limited cutaneous SSc and 49 (39·5%) had diffuse cutaneous SSc. Also included were 25 patients with Sjögren syndrome (SjS), 29 with rheumatoid arthritis (RA), 38 with SLE and 53 healthy controls. Enzyme-linked immunosorbent assays with high- and low-salt buffers were used to measure anti-C1q antibodies and CICs. The former allows only anti-C1q antibody binding to C1q and the latter also allows IgG Fc to bind to C1q. RESULTS: Anti-C1q antibodies were present in 20 of 124 (16·1%) patients with SSc: five had high levels (> 80 RU mL-1 ) and 10 (50%) had moderate levels (40-80 RU mL-1 ). Anti-C1q antibodies were also present in one of 25 (4%) patients with SjS, one of 29 (3%) with RA (P < 0·05 for both) and three of 53 (6%) healthy controls (P < 0·01). Anti-C1q antibodies were detected in 13 of 38 (34%) patients with SLEs. Anti-C1q antibodies were more frequent in male than female patients with SSc (P = 0·005); this association remained after multivariate regression analysis. Anti-C1q antibody level was the most important factor in predicting the presence of pulmonary fibrosis, and the second most important in predicting pulmonary arterial hypertension. Fourteen patients with SSc (11·3%) had CICs. CONCLUSIONS: Anti-C1q autoAbs were frequently detected in patients with SSc, and their high levels predict the co-occurrence of pulmonary fibrosis or pulmonary arterial hypertension.

The autoimmunity-oral microbiome connection.

To date, there is a major effort in deciphering the role of complex microbial communities, especially the oral and gut microbiomes, in the pathogenesis of various diseases. Increasing evidence indicates a key role for the oral microbiome in autoimmune diseases. In this review article, we discuss links of the oral microbiota to a group of autoimmune diseases, that is, Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), Crohn's disease (CD), and rheumatoid arthritis (RA). We particularly focus on factors that affect the balance between the immune system and the composition of microbiota leading to dysbiosis, loss of tolerance and subsequent autoimmune disease progression and maintenance.

Clinical and financial burden of active lupus in Greece: a nationwide study.

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need.

Infectomics and autoinfectomics: a tool to study infectious-induced autoimmunity.

The exposome represents all exogenous and endogenous environmental exposures that begin at preconception and carry on throughout life, while the microbiome reflects the microbial component of the exposome. We recently introduced the concept of infectome and autoinfectome as a means of studying the totality of infections throughout life that participate in the induction as well as the progression of autoimmune diseases in an affected individual. The investigation of the autoinfectome could help us understand why some patients develop more than one autoimmune disease, a phenomenon also known as mosaic of autoimmunity. It could also explain the infectious and autoantibody burden of various autoimmune rheumatic diseases. The close interplay between infections and the immune system should be studied over time, long before the onset of autoaggression and autoimmunity. Tracking down each individual's exposure to infectious agents (as defined by the autoinfectome) would be important for the establishment of a causative link between infection and autoimmunity.

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector-p53.

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy.

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

Long acting somatostatin analogues in combination to antineoplastic agents in the treatment of small cell lung cancer patients.

BACKGROUND: Long acting somatostatin analogues combined with platinum analogues have demonstrated an antiproliferative effect on growth of human SCLC xenographs. METHOD: 130 previously untreated SCLC patients--54 with limited disease (LD) and positive somatostatin receptors were included in the study. All patients performed 111In-Octreotide scanning before chemotherapy (CHT), every 3 months and up to 4 times. All patients were treated with paclitaxel 190 mg/m2+carboplatin AUC=5.5 for up to 6 cycles. 47/130 patients (Group A, control group) received only CHT. Forty eight hours after each CHT 43/130 patients (Group B) were also administered 30 mg somatuline® (lanreotide) by a single subcutaneous (s.c.) injection to stimulate somatostatin receptors (SSTRS) for 2 weeks. 40/130 patients (Group C) received 60 mg somatuline® autogel to stimulate SSTRS for 4 weeks. Patients in Groups A and B after the completion of the CHT continued maintenance therapy with somatuline. NSE, IGF1, VEGFA, VEGFC, VEGFR2, HER2 levels were monitored. In histological samples Bcl-2 and VEGF were also explored by immunohistochemistry. RESULTS: No statistically significant differences were observed between the 3 Groups regarding LD and extensive disease (ED) patient ratios, age and PS. Group B had a survival benefit in comparison to Groups A and C (p=0.029). LD patients of Group B had a significant benefit compared to Groups A and C (p=0.012, Breslow test). In LD Group B had a significant longer TTP (p=0.02) in comparison to Groups A and C. Adverse effects had no statistically significant difference between the Groups and toxicity was well managed. INTERPRETATION: Long acting somatostatin analogues could be used as an additive therapy in combination to antineoplastic agents in patients positive for somatostatin receptors. A dose of 30 mg improved survival only in LD SCLC patients.

Association of anti-CCP positivity and carriage of TNFRII susceptibility variant with anti-TNF-α response in rheumatoid arthritis.

OBJECTIVES: To investigate the possible influence of tumour necrosis factor-alpha (TNF), TNF receptor I (TNFRI) and TNF receptor II (TNFRII) gene polymorphisms on anti-TNF treatment responsiveness, stratified by autoantibody status. METHODS: A Greek multi-centre collaboration was established to recruit a cohort of patients (n=100) with active RA treated with anti-TNF drugs. TNF g.-238G>A (rs361525), g.-308G>A (rs1800629), g.-857C>T (rs1799724), TNFRI c.36A>G (rs4149584) and TNFRII c.676T>G (rs1061622) polymorphisms were genotyped by PCRRFLP assays. Serum RF and anti-CCP antibody status were determined using commercially available kits. Single-SNP, haplotype and stratification by autoantibody status analyses were performed in predicting response to treatment by 6 months, defined as the absolute change in DAS28. RESULTS: 31 patients (31%) were defined as non-responders due to failure to fulfill the DAS28 criteria. 79% and 66% were RF and anti-CCP positive, respectively. None of the genotyped SNPs was alone associated with responsiveness to drug treatment. However, after stratification by autoantibody status, carriage of TNFRII c.676G allele was associated with poorer response to drug treatment in anti-CCP positive patients (p=0.03), after 6 months of anti-TNF therapy. CONCLUSIONS: In concordance with previous studies, genetic polymorphisms alone cannot be used to safely predict clinical response to anti-TNF therapy however the combination of genetic factors and autoantibody status warrants further investigation in larger independent cohorts.

A 26-year-old male with mesothelioma due to asbestos exposure.

Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.

Ingested toothpick fistula of the ileum mimicking Crohn's disease.

Foreign body ingestion is an accidental or an intentional event, with most of the ingested foreign bodies passing spontaneously through the gastrointestinal tract without incidents. About 10-20% of them, especially long and sharp objects like toothpicks, will fail to pass through the entire gastrointestinal tract and may cause symptoms. Toothpick injury of the gastrointestinal tract is often associated with considerable morbidity and mortality. The complications that can be caused by toothpick ingestion are obstruction, perforation, hemorrhage, fistula formation, small bowel inflammation, sepsis and even death. Diagnosis of toothpick injury can be difficult as there are no specific physical findings or laboratory examinations which may aid the diagnosis and even imaging studies are of little help as wooden toothpicks are radiolucent. We report a rare case of incidental toothpick ingestion which caused an ileum fistula and mimicked Crohn's disease.

Ultrasonographic evidence of inflammation is frequent in hands of patients with erosive osteoarthritis.

OBJECTIVE: Erosive osteoarthritis (OA) (EOA) is considered an aggressive form of primary OA that is defined radiographically by intra-articular erosions of the inter-phalangeal joints of the hand and characteristic deformities. The aim of the present study was the sonographic investigation of hand small joints in patients with EOA and comparison of the imaging findings with conventional radiography (CR). METHOD: Twenty-two patients (20 women, mean age 62.5 years) with clinical and radiographic diagnosis of EOA formed our study group. A total of 660 joints were assessed by both radiographs and ultrasound (US). US and plain films were evaluated by two different physicians on a blinded fashion. Erosions, osteophytes and deformities were evaluated by both US and plain films. Synovial thickening, effusion, and power Doppler signal indicative of abnormal vascularity were recorded in each joint during US scanning. RESULTS: Erosions were detected in 231/660 (35%) small joints by US and in 115/660 (17.4%) small joints by conventional radiographs (P<0.05). Osteophytes were detected in 360/660 (54.5%) small joints by US, and in 310/660 (47.0%) small joints by conventional radiographs (P<0.05). Thickened synovium was detected in 19 of 22 patients and increased intra-articular power Doppler signal, indicative of active inflammation, was detected in 18 of 22 patients. Thickened synovium was found in 159/660 (24.1%), effusion in 119/660 (18%) and increased power Doppler in 148/660 (22.4%) small joints. Intra-observer kappa value for agreement regarding US was 0.81 and plain films 0.86. In 31 instances extensive finger tenosynovitis was also evident. CONCLUSION: In patients with EOA, US is a reliable and a more sensitive imaging modality than CR in detecting erosions and osteophytes. US detects inflammatory changes in small hand joints in the vast majority of patients with EOA and suggests that current treatment modalities are inadequate treatment for this disease.

Management of gastrointestinal bezoars: an analysis of 23 cases.

Bezoars (BZs) represent the most common foreign bodies of the gastrointestinal tract. Clinical symptoms varying from no symptoms to acute abdominal obstruction. Our goal is to present our experience with a review of the literature. In this study, 23 patients with BZs of the upper gastrointestinal system (GIS) were treated in the surgical department of two generals hospitals in northwest Greece. The size of BZs, localization, predisposing factors, clinical symptoms, morbidity, and mortality were analyzed. Conservative treatment, endoscopic procedures, and surgical treatment were also parameters under consideration. Nineteen patients presenting with phytobezoars and four female patients presented with psychological disorders and mental retardation with trichobezoars. More than one half of them (57%) had previous gastric surgery. Surgical morbidity rate was 28%, whereas the endoscopic morbidity was 11%. Mortality was 4% and 0% for the surgical and endoscopic groups, respectively. The differences in morbidity and mortality rates between the two groups were not statistically significant. BZs are commonly found in the stomach and small intestine, especially in patients who underwent previous gastric surgery. Small bowel obstruction is the most common complication. When uncomplicated, endoscopic or surgical removal of the BZs can be performed easy and effectively.

Effect of 5-fluorouracil plus interferon on the integrity of colonic anastomoses covering with fibrin glue.

BACKGROUND: It has been well established that the immediate postoperative intraperitoneal administration of chemotherapeutic agents such as 5-fluorouracil (5-FU) after curative colon resection for colon cancer destroys disseminated cancer cells and inhibits micrometastases but also inhibits anastomotic healing. On the other hand, the application of fibrin glue constitutes a physical barrier around the anastomosis and may prevent anastomotic leakage. The purpose of this experimental study was to determine the effect of 5-FU plus interferon (IFN)-alpha-2a on the integrity of colonic anastomoses covered with fibrin glue when injected intraperitoneally immediately after colon resection. MATERIALS AND METHODS: Sixty rats were randomized to one of four groups. After resection of a 1-cm segment of the transverse colon, an end-to-end sutured anastomosis was performed. Rats of the control and the fibrin glue groups were injected with 6 ml of 0.9% sodium chloride (NaCl) solution intraperitoneally. Rats in the 5-FU + IFN and the 5-FU + IFN + fibrin glue groups received 5-FU plus IFN intraperitoneally. The colonic anastomoses of the rats in the fibrin glue and in the 5-FU + IFN + fibrin glue groups were covered with fibrin glue. All rats were sacrificed on the 8th postoperative day, and the anastomoses were examined macroscopically. The bursting pressure measurements were recorded, and the anastomoses were graded histologically. RESULTS: Only the 5-FU + IFN group had anastomoses rupture, and the rupture rate (33%) in this group was significantly greater than in the other groups, where there were no ruptures (P = 0.015). The adhesion formations score was, on average, significantly higher in rats of the 5-FU + IFN group compared with the control group (P = 0.006) and the 5-FU + IFN + fibrin glue group (P = 0.010). Bursting pressures were significantly lower in the control group when compared to the fibrin glue and 5-FU + IFN + fibrin glue group (P < 0.001). Rats in the 5-FU + IFN + fibrin glue group developed significantly more marked neoangiogenesis than rats in the other groups. Inflammatory cell infiltration, collagen deposition, and fibroblast activity did not differ significantly among the four groups (P = 0.856, P = 0.192 and P = 0.243, respectively). CONCLUSION: The immediate postoperative intraperitoneal administration of 5-FU plus IFN impairs colonic healing. However, when the colonic anastomoses were covered with fibrin glue, the injection of 5-FU plus IFN had no adverse effects on the integrity of the anastomoses.

The healing of colon anastomosis covered with fibrin glue after early postoperative intraperitoneal chemotherapy.

BACKGROUND: After colon resection for colonic cancer, the administration of antineoplastic agents may prolong survival by killing residual cancer calls and preventing metastasis, but may also slow anastomotic healing. This study was designed to determine the effects of 5-fluorouracil (5-FU) and leucovorin (LEV), injected intraperitoneally, on the healing of colonic anastomoses with or without fibrin glue (FG) covering. METHODS: Sixty rats were randomized to one of four groups. After resection of a transverse colon segment, an end-to-end sutured anastomosis was performed. Rats in the 5-FU+LEV and the 5- FU+LEV+FG groups received 5-FU+LEV intraperitoneally. The colonic anastomoses of the rats in the FG group and in the 5-FU+LEV+FG group were covered with fibrin glue. All rats were killed on postoperative day 8. Bursting pressure measurements were recorded and the anastomoses were examined macroscopically and histologically. RESULTS: The leakage rate of the anastomoses was significantly different among groups. Specifically, the leakage rate was significantly higher in the 5-FU+LEV group (40%) than in the FG and in the 5-FU+LEV+FG groups where there were no leakages (p=0.017). The mean adhesion formation score was significantly higher in rats of the 5-FU+LEV group, compared to the control (p=0.023), the FG (p=0.006) and the 5-FU+LEV+FG (p=0.006) groups. Bursting pressures were significantly lower in the 5-FU+LEV group than in the other groups (p<0.001). Also, bursting pressures were significantly lower in the control group compared to the FG and 5-FU+LEV+FG groups (p<0.001). Rats in the 5-FU+LEV+FG group had significantly greater neoangiogenesis and fibroblast activity than those in the 5-FU+LEV group (p=0.025). CONCLUSION: The early intraperitoneal postoperative administration of 5-fluorouracil plus leucovorin impaired colonic wound healing. However, the application of fibrin glue prevented the deleterious effect of chemotherapy.

Early T cell activation in the skin from patients with systemic sclerosis.

OBJECTIVES: To determine if T cells in skin lesions in systemic sclerosis (SSc) express the early activation antigen CD69 that participates in cell-cell interactions. METHODS: Skin biopsy specimens from 17 patients with SSc were analysed by immunohistochemistry using the indirect peroxidase method and monoclonal antibodies for CD3 (T cell marker), CD69 (early T cell activation marker), and CD68 (macrophage marker). RESULTS: Mononuclear cells, containing mostly T cells and macrophages, were increased in SSc skin lesions and were present in perivascular areas. CD69 was expressed in these mononuclear cells. There was no correlation between the number of CD3+, CD69+, or CD68+ cells and the Rodnan skin score or disease duration. CONCLUSIONS: The expression of early T cell activation antigen CD69 in skin lesions suggests that T cells may actively participate in cell-cell contact with fibroblasts to promote fibrosis.

Healing of colon anastomoses covered with fibrin glue after immediate postoperative intraperitoneal administration of 5-fluorouracil.

PURPOSE: The aim of this experimental study was to investigate whether covering the colonic anastomoses with fibrin glue can protect the colonic healing from the adverse effects of 5-fluorouracil (5-FU), when it is injected intraperitoneally immediately after colon resection. METHODS: Sixty-four rats were randomized to one of four groups. After resection of a 1-cm segment of the transverse colon, an end-to-end sutured anastomosis was performed. Rats of the control group and the fibrin glue group were injected with 6 ml of solution 0.9 percent NaCl intraperitoneally. Rats in the 5-FU and the 5-FU + fibrin glue groups received 5-FU intraperitoneally. The colonic anastomoses of the rats in the fibrin glue group and in the 5-FU + fibrin glue group were covered with fibrin glue. All rats were killed on the 8th postoperative day and the anastomoses were examined macroscopically. The bursting pressure measurements were recorded and the anastomoses were graded histologically. RESULTS: The leakage rate of the anastomoses was significantly higher in the rats of the 5-FU group than in those of the fibrin glue group and those of the 5-FU + fibrin glue group (37.5 percent vs. 0 percent, P = 0.020). The adhesion formation score was significantly higher in rats of the 5-FU group than in the other groups. Bursting pressures were also significantly lower in the 5-FUgroup than in the other groups ( P < 0.001). Rats in the 5-FU + fibrin glue group developed significantly more marked neoagiogenesis than rats in the other groups. Rats in the 5-FU + fibrin glue group also presented significantly more fibroblast activity than those in the 5-FU group. ( P = 0.004) CONCLUSIONS: The immediate postoperative, intraperitoneal administration of 5-FU inhibited wound healing. However, when the colonic anastomoses were covered with fibrin glue, the injection of 5-FU had no adverse effects on the healing of the anastomoses.