Invasive Esophageal Candidiasis with Chronic Mediastinal Abscess and Fatal Pneumomediastinum.

BACKGROUND Invasive candidiasis is a potential problem for patients receiving long-term immunosuppressive treatment. Psoriatic arthritis is one of many chronic diseases that can be successfully treated with immunosuppressive drugs, in spite of a documented and accepted risk for infectious complications. Critical awareness of possible infection must be part of the surveillance of such patients. CASE REPORT This is the case of a 68-year-old Norwegian male, treated with long-term immunosuppression for psoriatic arthritis, hospitalized with acute subcutaneous and mediastinal emphysema of unknown cause. He died of acute respiratory failure with circulatory collapse shortly after admission. The autopsy revealed mediastinal and subcutaneous emphysema and a mediastinal abscess containing Candida with probable entrance from the esophagus. CONCLUSIONS We consider invasive candidiasis of the esophagus to be the cause of both the chronic abscess and the acute mediastinal emphysema. This case illustrates the importance of awareness of invasive candidiasis as a possible complication in a patient with long-term immunosuppression.

Lecithin: Cholesterol Acyltransferase (LCAT) Deficiency: renal lesions with early graft recurrence.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare metabolic disease with lipid deposition in several organs. The authors report a man with hypertension and proteinuria. Renal biopsy revealed glomerular changes, including peculiar thrombus-like deposits, consistent with LCAT deficiency. He was found to be compound heterozygous for two mutations of the LCAT gene. He received a kidney graft from his father. The authors also describe LCAT deficiency-related lesions in the explanted native kidneys and in biopsies at 2 days, 6 weeks, and 1 year after transplantation. The morphology of this disease is characteristic, and the diagnosis should be suspected from the ultrastructural findings.

Intra-abdominal administration of bevacizumab diminishes intra-peritoneal adhesions.

AIM: To determine the effect of a single dose of bevacizumab on adhesion formation in the rat cecum abrasion model. METHODS: The cecum and parietal peritoneum of 38 male Wistar rats were abraded to promote adhesion formation. The rats were randomized into 2 groups: group 1 received bevacizumab (2.5 mg/kg) intraperitoneally, and group 2 received saline. On day 30 animals were killed, adhesions scored, and histopathological samples taken. RESULTS: There was no wound dehiscence; there were 2 incision hernias (5.3%), 1 per group. Thirty-seven animals developed adhesions (97.4%). Adhesion grade and severity scores were significantly different between groups 1 and 2 at 2.7:1.6 (P = .018) and 3.8:2.7 (P = .007), respectively. There was no difference in adhesion square area (27.7:25.0%; P = .16), location (P = 1.00), or number (2.1:1.3; P = .06). Histopathology confirmed the statistical difference between groups (P = .049), and a highly significant correlation between results was shown (r = .758; P = .0001). CONCLUSION: A single dose of intraperitoneal bevacizumab significantly reduces grade and severity of abdominal adhesions in the cecum abrasion rat model.

[A woman with hemorrhagic shock]. / En kvinne med blødningssjokk.

BACKGROUND: Acute upper gastrointestinal bleeding may be a life-threatening condition that calls for immediate diagnosis and action. MATERIAL AND METHODS: We present an 82-year-old female patient with haematemesis, who during the first few minutes after admission developed haemorrhagic shock. At emergency laparotomy, a profuse bleeding in the duodenum was found. During surgery the patient developed cardiovascular collapse and died. The patient had a previous diagnosis of duodenal ulcer. She was, furthermore, diagnosed with an abdominal aortic aneurysm developing at the cranial anastomosis of an aorto-bifemoral bypass performed seventeen years earlier. An autopsy was performed and confirmed the clinical suspicion of an aorto-duodenal fistula. RESULTS AND INTERPRETATION: An aorto-enteric fistula represents a direct communication between the aorta and the intestinal lumen; it can be primary or secondary. Secondary aorto-enteric fistulae are complications of reconstructive procedures on the abdominal aorta. Based on register data, approximately three patients with this condition could be expected per year in Norway (incidence 1.6 %). Patients with severe gastric-intestinal bleeding and previous aortic reconstruction represent an identifiable group that should be referred directly to hospitals with competence in vascular surgery.

Computerized image analysis vs semiquantitative scoring in evaluation of kidney allograft fibrosis and prognosis.

BACKGROUND: Chronic morphological changes in the kidney allograft predict long-term graft function, but there are few studies comparing different methods in assessing chronic lesions. In the present study, we evaluated allograft cortical interstitial fibrosis, and compared semiquantitative assessment with computerized image analysis of Sirius red-stained collagen in prediction of graft prognosis. METHODS: Sections were obtained from a series of 1-year protocol living donor kidney graft biopsies (n = 33) and their corresponding baseline specimens (n = 32). At light microscopy, the biopsies were scored for interstitial fibrosis as a percentage of involved tubulointerstitium according to the Banff schema. Quantitation of cortical fractional interstitial fibrosis volume (Vint) was performed with computerized image analysis on coded sections stained with Sirius red. The results were correlated with kidney function at 8-10 years after transplantation, and with late graft loss. RESULTS: There was a significant correlation between the semiquantitative and quantitative methods for measuring cortical interstitial fibrosis in all the biopsies (n = 65, percentage area vs Vint: R = 0.439, P = 0.0003). The correlation further improved when analysing the baseline specimens separately (n = 32, R = 0.704, P<0.0001) and was still significant, but less precise for the 1-year biopsies (n = 33, R = 0.384, P = 0.0274). One-year semiquantitative fibrosis (percentage area) was correlated to serum creatinine at 8-10 years (P = 0.010) and to late graft loss (P = 0.0445). The 1-year Vint values for interstitial fibrosis showed a similar trend but did not reach statistical significance in prediction of long-term graft function. CONCLUSIONS: Image analysis quantitation of interstitial collagen with Sirius red corresponded well to light microscopic semiquantitative assessment of interstitial fibrosis. In prediction of long-term graft function, the semiquantitative method was superior, indicating that accumulation of matrix molecules other than fibrillary collagens, oedema and inflammation are also important in graft prognosis.

Antibody-mediated rejection criteria - an addition to the Banff 97 classification of renal allograft rejection.

Antibody-mediated rejection (AbAR) is increasingly recognized in the renal allograft population, and successful therapeutic regimens have been developed to prevent and treat AbAR, enabling excellent outcomes even in patients highly sensitized to the donor prior to transplant. It has become critical to develop standardized criteria for the pathological diagnosis of AbAR. This article presents international consensus criteria for and classification of AbAR developed based on discussions held at the Sixth Banff Conference on Allograft Pathology in 2001. This classification represents a working formulation, to be revisited as additional data accumulate in this important area of renal transplantation.

International variation in histologic grading is large, and persistent feedback does not improve reproducibility.

Histologic grading systems are used to guide diagnosis, therapy, and audit on an international basis. The reproducibility of grading systems is usually tested within small groups of pathologists who have previously worked or trained together. This may underestimate the international variation of scoring systems. We therefore evaluated the reproducibility of an established system, the Banff classification of renal allograft pathology, throughout Europe. We also sought to improve reproducibility by providing individual feedback after each of 14 small groups of cases. Kappa values for all features studied were lower than any previously published, confirming that international variation is greater than interobserver variation as previously assessed. A prolonged attempt to improve reproducibility, using numeric or graphical feedback, failed to produce any detectable improvement. We then asked participants to grade selected photographs, to eliminate variation induced by pathologists viewing different areas of the slide. This produced improved kappa values only for some features. Improvement was influenced by the nature of the grade definitions. Definitions based on "area affected" by a process were not improved. The results indicate the danger of basing decisions on grading systems that may be applied very differently in different institutions.

Complement activation in early protocol kidney graft biopsies after living-donor transplantation.

BACKGROUND: To gain insight into complement activation in kidney grafts, we studied the deposition of components from all complement pathways in protocol biopsies from living-donor recipients that were taken 1 week (median 7 days) after transplantation. METHODS: Graft protocol biopsies (n=37) were taken consecutively and stained for two-color immunofluorescence, with antibodies to C4d, C3, C1q, factor B, C6, terminal C5b-9 complement complex, mannose-binding lectin (MBL), and MBL-associated serine protease-1, combined with an endothelial marker. Light and electron microscopy were performed in all cases. Clinical acute rejection (AR), graft loss, and long-term kidney function were recorded. Baseline biopsies from 15 of the patients served as controls. RESULTS: Endothelial C4d deposition was demonstrated in peritubular capillaries in 11 of 37 cases (30%), of which 9 of 11 (82%) experienced clinical AR but only 6 of 11 (55%) experienced AR as defined by histopathologic criteria. Biopsies from three patients, two with early graft loss, showed diffuse global C4d in the glomerular endothelium with codeposition of C3 in all patients and MBL-associated serine protease-1 in one patient. Focal peritubular capillary C3 deposition was found in two additional C4d-positive cases with AR. No posttransplant deposition was demonstrated for the other components. CONCLUSIONS: Early diffuse C4d deposition in the kidney graft capillaries is closely related to acute humoral rejection, whereas focal staining may occur with mild AR or, rarely, without rejection. Codeposition of C3 indicates early AR with a higher risk of graft loss. In most cases, activation was limited to C4d, indicating efficient in situ regulation of complement activation.

The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients.

Cytomegalovirus (CMV) infection and disease are potential risk factors for acute allograft rejection in renal transplant recipients. The present study specifically addresses this issue. From October 1994 to July 1997, 477 consecutive renal allograft recipients (397 first transplants and 80 retransplants) were included in the study. CMV infection (cytomegalovirus pp65 antigen in leukocytes) and disease (infection and clinical symptoms or signs of disease) were examined prospectively for 3 months. No CMV prophylaxis was given, and CMV disease was treated with intravenous (i.v.) ganciclovir. The retransplantation of four patients transplanted twice during the study and 22 patients receiving kidneys from human leucocyte antigen (HLA)-identical siblings were excluded from statistical analysis. Rejections were evaluated clinically [277(61%)] and 173 (38%) also had a biopsy verified rejection. CMV infection occurred in 64% of the patients and 24% experienced CMV disease. In a multiple time-dependent Cox analysis, CMV infection and CMV disease were independent significant predictors for clinical acute rejections, RR = 1.6 (1.1-2.5, p = 0.02) and RR = 2.5 (1.2-5.1, p = 0.01), respectively. Among 173 patients with biopsy verified rejection, 72% of the patients had tubulointerstitial rejection whereas 28% had a vascular rejection. CMV disease, but not CMV infection was a predictor of tubulointerstitial rejection, RR = 3.1 (1.1-9.3, p = 0.04). CMV infection and disease are independent risk factors for clinical acute rejection in kidney allograft recipients. CMV disease is an independent risk factor for biopsy verified acute tubulointerstitial rejection in kidney allograft recipients.