Multivisceral intestinal transplantation: Surgical pathology

We report the diagnostic surgical pathology of two children who underwent multivisceral abdominal transplantation and survived for 1 month and 6 months. There is little relevant literature, and diagnostic criteria for the various clinical possibilities are not established; this is made more complicated by the simultaneous occurrence of more than one process. We based our interpretations on conventional histology, augmented with immunohistology, including HLA staining that distinguished graft from host cells in situ. In some instances functional analysis of T cells propagated from the same biopsies was available and was used to corroborate morphological interpretations. A wide spectrum of changes was encountered. Graft-versus-host disease, a prime concern before surgery, was not seen. Rejection was severe in 1 patient, not present in the other, and both had evidence of lymphoproliferative disease, which was related to Epstein-Barr virus. Bacterial translocation through the gut wall was also a feature in both children. This paper documents and illustrates the various diagnostic possibilities.. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Parents' underestimation of their child's weight status. Moderating factors and change over time: A cross-sectional study

BACKGROUND: Parents' underestimation of their child's weight status can hinder active participation in overweight prevention programs. We examined the level of agreement between the parents' perception of their child's weight status and the child's actual weight status, moderating factors, and change over time. METHODS: This cross-sectional study used data collected in 2009 (n = 8105), 2013 (n = 8844) and 2017 (n = 11,022) from a community-based survey conducted among parents of children age 2-12 years in the Netherlands. Parents classified their perception of their child's weight status on a 5-point Likert scale. In 2009 and 2013, the child's BMI was calculated from self-reported data by parents. The level of agreement between the parent's perception of the weight status and the actual weight status was examined using Cohen's kappa. The role of demographic factors on parents' perception were examined using logistic regression. RESULTS: In 2009, 2013 and 2017, 6%, 6% and 5% of the parents, respectively, classified their child as heavy/extremely heavy. In 2009 and 2013, 64.7% and 61.0% of parents, respectively, underestimated the weight status of their overweight child. This was even higher among parents of obese children. Overall, the agreement between the parents' perception and the actual weight status improved from 2009 (kappa = 0.38) to 2013 (kappa = 0.43) (p<0.05), but remained unsatisfactory. The parents' underestimation of their child's overweight/obesity status was associated with the child's age in 2009 and 2013 (2-7 years; OR: 0.18), the child's gender in 2009 (male; OR: 0.55), and the parents' education level in 2009 (middle and high education; OR: 0.56 and 0.44 respectively). CONCLUSIONS: Parents' underestimation of their child's weight status remains alarmingly high, particularly among parents of young, obese children. This underestimation is a barrier to preventing childhood overweight/obesity. Healthcare professionals should take this underestimation into consideration and should actively encourage parents to take steps to prevent overweight/obesity in their children

Nonpulmonary Outcomes of Asbestos Exposure

The adverse pulmonary effects of asbestos are well accepted in scientific circles. However, the extrapulmonary consequences of asbestos exposure are not as clearly defined. In this review the potential for asbestos to produce diseases of the peritoneum, immune, gastrointestinal (GIT), and reproductive systems are explored as evidenced in published, peer-reviewed literature. Several hundred epidemiological, in vivo, and in vitro publications analyzing the extrapulmonary effects of asbestos were used as sources to arrive at the conclusions and to establish areas needing further study. In order to be considered, each study had to monitor extrapulmonary outcomes following exposure to asbestos. The literature supports a strong association between asbestos exposure and peritoneal neoplasms. Correlations between asbestos exposure and immune-related disease are less conclusive; nevertheless, it was concluded from the combined autoimmune studies that there is a possibility for a higher-than-expected risk of systemic autoimmune disease among asbestos-exposed populations. In general, the GIT effects of asbestos exposure appear to be minimal, with the most likely outcome being development of stomach cancer. However, IARC recently concluded the evidence to support asbestos-induced stomach cancer to be “limited.” The strongest evidence for reproductive disease due to asbestos is in regard to ovarian cancer. Unfortunately, effects on fertility and the developing fetus are under-studied. The possibility of other asbestos-induced health effects does exist. These include brain-related tumors, blood disorders due to the mutagenic and hemolytic properties of asbestos, and peritoneal fibrosis. It is clear from the literature that the adverse properties of asbestos are not confined to the pulmonary system

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

The limited efficacy of cyclosporine in preventing rejection and graft-versus-host disease in orthotopic small bowel transplantation in rats

The effect of different schedules of cyclosporine treatment on the survival of small bowel allografts was studied in rats. The administration of a short course of CsA (15 mg/kg on days 0,1,2,4, and 6) had no beneficial effect on graft-vs.-host disease and survival time of the recipient compared with untreated controls. CsA, 25 mg/ kg for 1 or 2 weeks prolonged survival significantly (38.3±3.8 and 42.5±2.7 vs. 16.6±2.7, P&lt;0.0l). When combined with maintenance therapy, 15 mg/kg of CsA 3 times weekly until day 100, only 7 of 30 rats survived more than 100 days. In addition, GVHD was not consistently abrogated in these groups. Only high doses of CsA (25 mg/kg on days 0-6, 15 mg/kg on days 7-13, followed by maintenance therapy) could prevent the onset of GVHD, although the survival time of the transplants was not prolonged compared with untreated controls due to a toxic side effect of CsA on the transplants. It can be concluded that CsA used as monotherapy is ineffective in consistently ameliorating GVHD and rejection in the WAG-BN rat model. This model exhibits at least some of the immunological problems seen in large animal models and can be useful in studying combinations of immunosuppressive drugs or methods that may be applicable to small bowel transplantation in man.</p

Total orthotopic allogeneic small bowel transplantation in rats:Attempts to ameliorate the graft-versus-host disease by irradiation and transfusions of the donor

The effect of pretransplant specific blood transfusions and irradiation of the donor were studied in total orthotopic small bowel transplantation in rats, with the aim of ameliorating the graft-versus-host reaction. Syngeneic transplantation with or without irradiation of the donor with 10 Gy showed that small bowel transplantation is compatible with a normal nutritional status, when no rejection is involved. Transplantation in the histoincompatible WAG-to-BN combination without pretreatment resulted in rejection of the small bowel grafts in 16.6±2.7 days. Pretreatment with 3 BN blood transfusions to the WAG donor did not prolong the survival time; surprisingly, the transfusions induced a more-severe GVH reaction. Irradiation of the donor with 10 Gy was very effective in ameliorating the GVH disease, but the absence of the immunosuppressive effect of the GVH disease did lead to an accelerated graft rejection (7.5±0.9 days).</p

Effects of donor pretreatment with antilymphocyte serum and cyclosporin on rejection and graft-versus-host disease after small bowel transplantation in immunosuppressed and nonimmunosuppressed rats

After fully allogeneic small bowel transplantation, both graft-versus-host disease (GVHD) and rejection may occur. Donor pretreatment may prevent GVHD, but this sometimes leads to accelerated graft rejection. To study a possible balance between GVHD and rejection, fully allogeneic total orthotopic small bowel transplantation was performed in rats using the WAG-to-BN donorhost combination. Untreated control grafts were rejected in 16.6±2.7 days (mean ±SEM), and 35% of the animals had mild, transient GVHD. Pretreatment of the donor with antilymphocyte serum on days-2 and-1 before grafting, either intravenously or intraperitoneally, completely eliminated the occurrence of clinical GVHD but led to significantly shortened survival times (12.3±0.8 and 10.3±0.9 days, respectively). Donor pretreatment with 50 mg/kg cyclosporin (CyA) on days-2 and-1 prolonged graft survival significantly to 22.1 days but had no significant effect on the incidence of GVHD. Administration of 25 mg/kg CyA on days 0, 1, 2, 4, and 6 after grafting prolonged survival to 38.3 days with no evidence of GVHD. Pretreatment of the donor with antilymphocyte serum (ALS), combined with the same postoperative, short-term CyA regimen, increased survival to more than 50 days, again with no evidence of GVHD. When CyA was used as both donor pretreatment and postoperative therapy, there was no survival advantage compared to the use of postoperative CyA alone. These results show that an in vivo balance between GVHD and rejection exists and that abrogation of GVHD leads to accelerated rejection. Immunosuppression of the recipient may overrule this accelerated rejection while preserving the beneficial effect of donor pretreatment: elimination of clinical GVHD.</p