A regional EUS service using a collaborative network.

Endoscopic ultrasound (EUS) is increasingly used in the management of hepatobiliary lesions, allowing staging and tissue acquisition. It is operator-dependent, and fine needle aspiration (FNA) of solid lesions provides an auditable standard; high-volume centres have shown excellent results for solid pancreatic lesion FNA with sensitivities of 92%-97%. The British Society of Gastroenterology guidelines stress that clinical quality should determine service provision, with geographical accessibility a secondary consideration. We set up the Wessex EUS network, working from a single hepatobiliary (HPB) pancreatic multidisciplinary team, with EUS provided in four local centres providing agreed standards and audit. Pancreatic solid lesion FNA results showed a pooled sensitivity of 94%, comparable with high-volume single centres. This demonstrates a network with good clinical governance is a plausible solution to providing a specialist service such as EUS and may be a roadmap that other specialist services under pressure could follow.

Survival and dependence on home parenteral nutrition: experience over a 25-year period in a UK referral centre.

BACKGROUND: Home parenteral nutrition (HPN) is the standard treatment for severe intestinal failure in the United Kingdom. AIM: To review long-term survival and ongoing HPN dependence of patients receiving HPN treated at a specialist UK referral centre. METHODS: Medical records of patients commenced on HPN between 1979 and 2003 were reviewed retrospectively. Regression analysis was employed to identify factors associated with poor prognosis. RESULTS: Case notes of 188 patients were reviewed. Overall probability of survival was 86%, 77%, 73% and 71% at 1, 3, 5 and 10 years after starting treatment. In multivariate analysis, association was seen between mechanism of intestinal failure and survival: short bowel syndrome associated with a favourable prognosis, and intestinal dysfunction, dysmotility and obstruction with poorer prognoses. There was an association between increasing age and poor prognosis, but increased mortality was also seen in the youngest age groups. Only 9% of deaths were due to complications of HPN. Continued HPN dependence was 89%, 87%, 84% and 84% at 1, 3, 5 and 10 years in survivors. CONCLUSIONS: Long-term survival of patients receiving HPN remains better than that reported after intestinal transplantation. Mortality predominantly relates to underlying disease rather than complications of HPN.

A pilot study investigating a novel subcutaneously implanted pre-cellularised scaffold for tissue engineering of intestinal mucosa.

Tissue engineering of the small intestine offers an alternative to long-term intravenous nutrition and transplantation in patients with intestinal failure. Initial work, although encouraging, is limited by the volume of neonatal tissue required to produce a small neomucosal cyst. Our novel approach is to implant tubular poly-lactide-co-glycolide (PGLA) foam scaffolds subcutaneously. The aim of this study was to investigate whether these scaffolds would support growth of intestinal neomucosa. PGLA scaffolds were implanted subcutaneously into 8 Lewis rats; after 5 weeks, 'organoid units' were injected into the lumens. Tissue was assessed histologically after harvesting and quantitative immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGF-R2), fibroblast growth factor basic (bFGF) and fibroblast growth factor receptor 2 (FGF-R2). At 4 weeks post organoid unit implantation, clearly recognisable mucosa and submucosa was present on the luminal surface of the scaffold. Densities of VEGF and VEGF-R2 positive cells increased with time post organoid unit implantation. This pilot study demonstrates that it is possible to tissue engineer small intestinal neomucosa using subcutaneously implanted PLGA scaffolds. The yield of the process compares favourably to the published literature. Further work is required to optimise the technique.

Prolonged maintenance of neointestine using subcutaneously implanted tubular scaffolds in a rat model.

Tissue-engineered small intestine offers a possible alternative to long-term parenteral nutrition or intestinal transplantation in patients with short bowel syndrome. The aim of this study was to investigate the prolonged development of neointestine grown on subcutaneously implanted scaffolds. Tubular polylactide-coglycolide (PLGA) scaffolds were implanted into adult Lewis rats. Four weeks after scaffold implantation, a suspension of organoid units was delivered to the lumen of each scaffold. Organoid units were manufactured from small intestine harvested from neonatal Lewis rats by partial digestion using collagenase and dispase. Scaffolds were removed at 4, 8, and 12 weeks after organoid unit implantation, processed to paraffin, and sectioned. Hematoxylin and eosin staining demonstrated well-developed and well-differentiated intestinal mucosa and a vascularised submucosa within the scaffolds at 4, 8, and 12 weeks. Appearances were similar to native small intestine. Immunohistochemistry performed using primary antibody against proliferating cell nuclear antigen, a marker for cellular proliferation, demonstrated positively staining cells within the mucosa and submucosa at all time points. In the mucosal layer these positively staining cells were found primarily in the crypts. These findings show that neointestinal mucosa can be maintained for at least 12 weeks on a subcutaneous PLGA scaffold, and the presence of actively proliferating cells at 12 weeks suggests potential for further development beyond this.

Parenteral nutrition: ethical and legal considerations.

Parenteral nutrition is an expensive therapeutic modality that is used to treat patients with intestinal failure. The benefit it offers in terms of life prolongation needs to be weighed against its risks and burdens. Through the use of descriptive clinical vignettes, this article illustrates the ethical and legal principles that underpin decisions to administer and, more importantly, to withhold or withdraw parenteral nutrition.

Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.

Transplantation of the small bowel across MHC and non-MHC disparities in the rat.

Using congenic strains of rats, the effect on the rejection of small bowel transplants across isolated major histocompatibility complex (MHC) and nonMHC antigenic disparities was examined. The medial survival time of small bowel grafts across MHC differences in the LEW anti-LEW.1N and LEW.1N anti-LEW strain combinations was 14 and 12 days, respectively. The median survival time across the nonMHC antigenic difference in the BN anti-DA.1N strain combination was 20 days, which was significantly longer than the rejection time across the MHC differences (P less than 0.005). Both hemagglutinating and cytotoxic antibodies were produced in all three strain combinations, but the magnitude of the response varied considerably and did not correlate with the time of rejection. In the case of MHC differences, the antibody was directed against both class I and class II antigens, and with the nonMHC difference, the greatest response was directed against the major blood group antigen RT2.

Acute and chronic pancreatitis--diseases on the rise: a study of hospital admissions in England 1989/90-1999/2000.

BACKGROUND: The number of hospital admissions for acute and chronic pancreatitis increased in Britain from the 1960s to the 1980s. AIMS: To determine time trends in acute and chronic pancreatitis for hospital admissions from 1989/90 to 1999/2000, mortality from 1979 to 1999, and various indices of alcohol consumption. METHODS: Hospital Episode Statistics for admissions were obtained from the Department of Health and mortality data from the Office for National Statistics. Alcohol consumption data were obtained from the General Household Survey. RESULTS: Between 1989/90 and 1999/2000, age-standardized hospital admission rates for acute pancreatitis increased by 43%, whilst those for chronic pancreatitis rose by 100%. The proportions of admissions requiring surgical operations increased for acute pancreatitis, but declined for chronic pancreatitis. Case fatality rates for acute pancreatitis declined, but mortality statistics showed no significant change. The proportion of women who drank more than 14 units of alcohol a week also increased. CONCLUSIONS: There has been a steady increase in admission rates for both acute and chronic pancreatitis over the study period, and these conditions will become an increasingly important part of the workload of the gastroenterologist.

The effects of a hyperosmolar intravenous contrast medium on blood viscosity.

The effects of the hyperosmolar contrast medium, diatrizoate meglumine (Renografin-76) on blood viscosity and other metabolic parameters were measured in 20 immature piglets. Intravenous contrast medium caused a significant (P less than .5) increase in serum osmolality, cardiac output, and urine output, and a decrease in hematocrit. There was a fall in blood viscosity that was not statistically significant. These changes, which are attributed to an acute shift of fluid into the hyperosmolar vascular compartment, were greatest at 3 minutes following injection and subsequently returned towards baseline levels. We conclude that blood viscosity is not increased following intravenous injection of hyperosmolar radiocontrast media.

Renal venous thrombosis in infants and children.

Urgent nephrectomy was once considered standard therapy for renal venous thrombosis, but recently nonoperative therapy has been advised. To examine this trend more closely, we reviewed 46 cases of renal venous thrombosis seen at the Children's Hospital of Pittsburgh (Pa) over the last 32 years. Earlier, diagnosis was frequently supported by intravenous pyelography, which was 79% accurate. More recently, sonography confirmed the diagnosis with 92% accuracy. Of 21 patients diagnosed during life, 4 were treated operatively and 3 survived. Of 17 patients treated nonoperatively, 14 (82%) survived, including 5 with bilateral disease. Since 1978, of the 10 patients treated nonoperatively, 9 have survived with no long-term morbidity. Our experience confirms that early diagnosis with sonography followed by supportive nonoperative therapy offers the best chance for success in patients with renal venous thrombosis.

Microbial translocation in neonates and infants receiving long-term parenteral nutrition.

OBJECTIVE: To explore whether episodes of endogenous septicemias due to microbial translocation are clinically relevant in neonates and infants who are receiving long-term parenteral nutrition (PN). DESIGN: Prospective observational cohort study of 2 years. SETTING: Neonates and infants who underwent surgical procedures and required PN because of gastrointestinal abnormalities. MEASUREMENTS: Surveillance cultures of the oropharynx and gut were obtained at the first of PN and thereafter twice each week. These cultures were processed for all microorganisms, except for coagulase-negative staphylococci, in a semiquantitative manner to detect overgrowth. A blood sample was taken for culture from both the central venous line and peripheral vein on clinical indication only. Microbial translocation was diagnosed when the microorganisms that were isolated from the blood sample were also carried in the throat and/or rectum within the 2 weeks preceding the episode of septicemia. MAIN RESULTS: Of 94 infants, 10 (11%) experienced 24 episodes of septicemia (ie, 7.3 septicemic episodes per 1000 days of PN). Six infants experienced 15 episodes of microbial translocation due to enteric microorganisms, including Escherichia coli, Klebsiella, Candida species, and enterococci. Microbial translocation occurred after a median of 58 days of PN (range, 32 to 286 days). The enteric organisms that caused septicemia were always present in the throat and/or rectum and in high concentrations ( > 10(5) colony-forming units per gram [ie, overgrowth]) in 60% of the translocation episodes. All but one episode occurred in infants with an abnormal serum bilirubin level ( > 17 mumol/L [0.99 mg/dl]). CONCLUSIONS: In neonates and infants who are receiving PN, septicemia may be a gut-related phenomenon.

Rhabdomyosarcoma in Roberts syndrome.

A 23-month-old child diagnosed as having Roberts syndrome, born to consanguineous parents, developed a sarcoma botryoides. Cytogenetic evaluation of peripheral blood lymphocytes and tumor cells showed premature centromere separation, which is characteristic of Roberts syndrome.

Infection rates in surgical neonates and infants receiving parenteral nutrition: a five-year prospective study.

We performed a prospective, observational, cohort study on 208 surgical neonates and infants between 1992 and 1997. Surveillance cultures of the oropharynx and rectum were obtained at the start of parenteral nutrition and thereafter twice weekly. Blood cultures were taken on clinical indication only. Microbial translocation was diagnosed when the micro-organisms in the blood were not distinguishable from those carried in the oropharynx and/or rectum. Liver function was monitored weekly and when septicaemia was suspected. The incidence of septicaemia was 15%. The predominant micro-organisms (86%) were the low-level pathogens, coagulase-negative staphylococci and enterococci. Potential pathogens, including aerobic Gram-negative bacilli, were responsible for the remainder. Microbial translocation was responsible for 84% of septicaemic episodes in 76% of patients. The potential pathogens caused septicaemia significantly later than coagulase-negative staphylococci, at a time when liver function was significantly more impaired. In neonates and infants receiving parenteral nutrition, septicaemia is mainly a gut-derived phenomenon and requires novel strategies for prevention.

Gut overgrowth with abnormal flora: the missing link in parenteral nutrition-related sepsis in surgical neonates.

BACKGROUND AND AIMS: Patients receiving parenteral nutrition are at risk of septicaemia. Intestinal dysmotility and impaired gut immunity due to parenteral nutrition promote bacterial overgrowth. Gut overgrowth with aerobic Gram-negative bacilli (AGNB) impairs systemic immunity. The aim of this study was to determine the potential role of gut overgrowth with AGNB in the pathogenesis of septicaemia related to parenteral nutrition. METHODS: A prospective 5 y study of surgical infants less than 6 months of age was undertaken. Surveillance samples of the oropharynx and gut were obtained at the start of parenteral nutrition and thereafter twice weekly, to detect AGNB carriage. Blood cultures were taken on clinical indication only. RESULTS: Two-hundred and eight infants received parenteral nutrition for 6271 days (median 13 days, range 1-512 days). The incidence of AGNB carriage was 42%, whilst the septicaemia rate was 15%. Eighty-four percent of septicaemic infants carried AGNB, whilst 16% never carried AGNB (P<0.005). Carriage developed significantly earlier than septicaemia. CONCLUSIONS: The incidence of septicaemia was significantly greater in the subset of abnormal carriers. Although gut overgrowth with abnormal flora reflects illness severity, the fact that it preceded septicaemia implicates AGNB overgrowth, per se, as a contributory factor in the development of septicaemia related to parenteral nutrition. Prevention is unlikely to be successful if it ignores the abnormal flora.

Gall bladder contractility in neonates: effects of parenteral and enteral feeding.

The gall bladder size was measured in 30 newborn infants: 18 had been fed parenterally and 12 enterally. The two groups were comparable for gestational age, birthweight, postnatal age and study weight. Exclusion criteria were haemodynamic instability, septicaemia, abdominal disease and opioid treatment. Gall bladder size was measured at 15 minute intervals for 90 minutes using real-time ultrasonography and the volume calculated using the ellipsoid method. Parenterally fed infants had further measurements at 120, 150, and 360 minutes. The gall bladder was significantly larger in parenterally fed infants than in enterally fed infants (p = 0.0001). In enterally fed infants a 50% reduction in gall bladder volume was observed 15 minutes after starting the feed with a return to baseline volume by 90 minutes. In parenterally fed infants there was no gall bladder contraction. Such information may give insight into the pathophysiology of hepato-biliary complications during parenteral nutrition in infants.

Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia.

AIMS: To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH). METHODS: CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5 and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry. RESULTS: On day 20.5, eNOS expression was significantly reduced in CDH pups compared with normal control rats. Dexamethasone treated CDH pups had eNOS concentrations equivalent to those of normal animals. By day 21.5, however, there was no detectable difference in eNOS expression between the experimental groups. CONCLUSIONS: eNOS is deficient in near term (day 20.5) CDH rats. Dexamethasone restores eNOS expression in these animals to that seen in normal rat lungs. At term, the precise role of eNOS in the pathophysiology of CDH remains uncertain.

Energy requirements of surgical newborn infants receiving parenteral nutrition.

The energy requirement for mature newborn infants receiving total parenteral nutrition is approximately 100 kcal.kg-1.d-1. There is no necessity to increase the caloric intake after an uncomplicated operation. Energy requirements are affected by the maturity of the infant, the degree of operative stress, opioid medication, and the presence or absence of sepsis. In general, glucose intake should not exceed the resting energy expenditure. Glucose administration exceeding 18 g.kg-1.d-1 is associated with lipogenesis and reduced oxygenation of exogenous lipid. Resting energy expenditure varies widely between infants, and energy intake, based on clinical and biochemical monitoring, should be adjusted for individual patients.

Absence of hypermetabolism after operation in the newborn infant.

This study was designed to assess the effect of operative stress on resting energy expenditure (REE) in the newborn infant. In 13 neonates who had an uncomplicated abdominal, thoracic, or spinal operation, REE was measured both preoperatively and on the third postoperative day. The mean preoperative REE of 43.19 +/- 7.95 kcal/kg per day was not significantly different from the mean postoperative REE of 41.70 +/- 7.94 kcal/kg per day. Sixteen neonates had REE measured on the first, second, and seventh postoperative days. The mean postoperative REE values of 43.12 +/- 6.92, 42.41 +/- 7.58, and 46.33 +/- 6.89 kcal/kg per day at 1, 2, and 7 days, respectively, were not significantly different from the preoperative REE. There was no significant difference in oxygen consumption, carbon dioxide production, and respiratory quotient between the preoperative and postoperative groups. In this study, an uncomplicated operation did not increase REE in the neonate.

Ultrasonography as a method of nutritional assessment.

The composition of the upper arms of five healthy individuals was measured by anthropometry (AN), ultrasonography (US), and computerized tomography (CT). Measurements of midarm fat area (MAFA) and midarm muscle area (MAMA) by CT correlated well with AN and US, but both AN and US overestimated MAMA by 22.8 +/- 17% and 10 +/- 12%, respectively, (mean +/- SD). The overestimate was largest with AN because with this method bone area cannot be excluded. To evaluate the usefulness of US measurements, 10 patients with advanced liver disease were studied. Measurement of MAFA by US, using triceps skinfold thickness as the standard, was found to be an accurate index of fat stores. MAMA measured by US correlated well with lean muscle mass, using creatinine height index as the standard. Ultrasonography is a reliable method of measuring body fat and lean muscle status.

Lifetime traumas and mental health: the significance of cumulative adversity.

This paper reports the community prevalence of 20 life traumas and considers their individual relevance as risk factors for psychiatric disorder. Also presented is the first evidence on the mental health significance of cumulative adversity as indexed by a count of lifetime exposure to a wide array of potentially traumatic events. The question of the importance of considering such events within efforts to assess variations in life stress is also examined. Our results demonstrate clear relationships between many traumatic events and, especially, accumulated lifetime trauma experience and both psychological distress and psychiatric disorder. That these relationships persist with temporal priority controlled - and net of the effects of parental psychopathology - suggest the causal relevance of major lifetime events and the conclusion that they represent on important dimension of increased mental health risk. From these findings and from evidence for the significance of traumas in disorder recurrence, it is contended that failure to take account of such events has resulted in the systematic underestimation of the role of stress exposure in accounting for variations in emotional distress and disorder.