JAG consensus statements for training and certification in oesophagogastroduodenoscopy.

Introduction: Training and quality assurance in oesophagogastroduodenoscopy (OGD) is important to ensure competent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for OGD training and certification. Methods: Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted with stakeholder representation from British Society of Gastroenterology, Association of Upper Gastrointestinal Surgeons, trainees and trainers. Recommendations on OGD training and certification were formulated following literature review and appraised using Grading of Recommendations Assessment, Development and Evaluation. These were subjected to electronic voting to achieve consensus. Accepted statements were incorporated into the updated certification pathway. Results: In total, 32 recommendation statements were generated for the following domains: definition of competence (4 statements), acquisition of competence (12 statements), assessment of competence (10 statements) and post-certification support (6 statements). The consensus process led to following certification criteria: (1) performing ≥250 hands-on procedures; (2) attending a JAG-accredited basic skills course; (3) attainment of relevant minimal performance standards defined by British Society of Gastroenterology/Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, (4) achieving physically unassisted D2 intubation and J-manoeuvre in ≥95% of recent procedures, (5) satisfactory performance in formative and summative direct observation of procedural skills assessments. Conclusion: The JAG standards for diagnostic OGD have been updated following evidence-based consensus. These standards are intended to support training, improve competency assessment to uphold standards of practice and provide support to the newly-independent practitioner.

Variation in outcomes and use of laparoscopy in elective inguinal hernia repair.

Background: The early outcomes of inguinal hernia repair in routine practice and the extent to which the laparoscopic approach is used are unknown. The aims of this study were to identify national benchmarks for early reoperation and readmission rates, to identify the degree to which the laparoscopic approach is used for elective hernia surgery in England, and to identify whether there is any variation nationally. Methods: All adults who underwent publically funded elective inguinal hernia repair in England during the six financial years from 2011-2012 to 2016-2017 were identified in the Surgeon's Workload Outcomes and Research Database (SWORD). Patients were grouped according to whether they had a primary, recurrent or bilateral hernia, and according to sex. Overall rates of readmission, reoperation and laparoscopic approach were calculated, and variation was assessed using funnel plots. Results: Some 390 777 patients were included. Overall, 11 448 patients (2·9 per cent) were readmitted to hospital as an emergency within 30 days of surgery and 2872 (0·7 per cent) had a further operation. Laparoscopic repair was performed for 65·5 per cent of bilateral inguinal hernias compared with 17·1 per cent of primary unilateral inguinal hernias, 31·3 per cent of recurrent hernia repairs and 14·0 per cent of primary unilateral hernias in women. The unadjusted readmission, reoperation and laparoscopy rates varied significantly between hospitals. Conclusion: The likelihood of a patient being readmitted to hospital, having an emergency reoperation or undergoing laparoscopic inguinal hernia repair varies significantly depending on the hospital to which they are referred. Hospitals and service commissioners should use this data to drive service improvement and reduce this variation.

Structure of proof of concept studies that precede a nonalcoholic steatohepatitis development program.

Surrogate endpoints for clinical proof of concept (POC) trials in nonalcoholic steatohepatitis (NASH) are based upon expert pathological review of liver biopsies. During early development, these long-term POC studies (≥48 weeks) add cost and time to the "Go/No Go" decision process. However, it is possible to conduct short-term noninvasive POC studies utilizing biomarkers and magnetic resonance imaging. Here, we discuss the use of shorter noninvasive POC studies relative to biopsy-driven studies for drug development in NASH.

Causes and management of a high-output stoma.

AIM: Patients with a high-output stoma (HOS) (> 2000 ml/day) suffer from dehydration, hypomagnesaemia and under-nutrition. This study aimed to determine the incidence, aetiology and outcome of HOS. METHOD: The number of stomas fashioned between 2002 and 2006 was determined. An early HOS was defined as occurring in hospital within 3 weeks of stoma formation and a late HOS was defined as occurring after discharge. RESULTS: Six-hundred and eighty seven stomas were fashioned (456 ileostomy/jejunostomy and 231 colostomy). An early HOS occurred in 75 (16%) ileostomies/jejunostomies. Formation of a jejunostomy (defined as having less than 200 cm remaining of proximal small bowel; n = 20) and intra-abdominal sepsis? obstruction (n = 14) were the commonest causes identified for early HOS. It was possible to stop parenteral infusions in 53 (71%) patients treated with oral hypotonic fluid restriction, glucose-saline solution and anti diarrhoeal medication. In 46 (61%) patients, the HOS resolved and no drug treatment was needed, 20 (27%) patients continued treatment, six (8%) of whom went home and continued to receive parenteral or subcutaneous saline, and nine died. Twenty-six patients had late HOS. Eleven were admitted with renal impairment and four had intermittent small-bowel obstruction. Eight patients were given long-term subcutaneous or parenteral saline and two also received parenteral nutrition. All had hypomagnesaemia. CONCLUSION: Early high output from an ileostomy is common and although 49% resolved spontaneously, 51% needed ongoing medical treatment, usually because of a short small-bowel remnant.

The "two-week wait" referral pathway allows prompt treatment but does not improve outcome for patients with oesophago-gastric cancer.

INTRODUCTION: The Two Week Wait Referral Service (2WW) has been implemented as a means of fast-tracking patients with suspected upper gastrointestinal cancers for endoscopy. Whether or not it impacts on the outcome of these patients is unclear. The aim of this study was to compare the outcome of patients referred through 2WW with that of patients with oesophago-gastric cancer identified through alternate referral pathways (routine, emergency). METHODS: The study population was 340 patients with oesophago-gastric carcinoma (gastric 154) diagnosed during the time period 01/2006-12/2007 at University Hospitals of Leicester NHS Trust. Data were collected prospectively by the MDT co-ordinator and analysed retrospectively. RESULTS: 135 of the 340 patients with oesophago-gastric cancer were diagnosed through the 2WW, 115 patients through routine referral pathways, and 90 patients were admitted on an emergency basis. Patients referred through 2WW had a median referral to 1st treatment time of 47 days (routine 79, emergency 28, p < 0.001 all group comparisons). The number of patients treated with potentially curative intent was 37 of 135 for the 2WW, 42 of 115 for the routine referrals and 10 of 90 for patients admitted as emergencies. The corresponding median survivals for the groups were 239 days (2WW), 405 days (routine) and 121 days (emergency), p < 0.001 (log rank). CONCLUSIONS: Referral by 2WW resulted in more rapid treatment than routine referral but this did not translate into an improvement in survival. This suggests that the targeting of endoscopy to patients with alarm symptoms is flawed and a less selective approach should be promoted if curable cancers are to be detected.

Enteral Clostridium difficile, an emerging cause for high-output ileostomy.

The loss of fluid and electrolytes from a high-output ileostomy (>1200 ml/day) can quickly result in dehydration and if not properly managed may cause acute renal failure. The management of a high-output ileostomy is based upon three principles: correction of electrolyte disturbance and fluid balance, pharmacological reduction of ileostomy output, and treatment of any underlying identifiable cause. There is an increasing body of evidence to suggest that Clostridium difficile may behave pathologically in the small intestine producing a spectrum of enteritis that mirrors the well-recognised colonic disease manifestation. Clinically this can range from high-output ileostomy to fulminant enteritis. This report describes two cases of high-output ileostomy associated with enteric C difficile infection and proposes that the management algorithm of a high-output ileostomy should include exclusion of small bowel C difficile.

The early use of PET-CT alters the management of patients with esophageal cancer.

INTRODUCTION: The routine use of positron emission tomography-computed tomography (PET-CT) in the staging of patients with esophageal carcinoma remains contentious, with conflicting reports of its benefit. In our unit, PET-CT has been used routinely in the staging of all patients considered for radical therapy (surgery or chemoradiotherapy). Our aim was to determine the frequency with which PET-CT influenced decision making in the management of patients with carcinoma of the esophagus or gastroesophageal junction. METHODS: CT, PET-CT, and outcome information were collected on 38 patients considered for radical therapy. Patient proformas, with and without PET-CT findings, were constructed and each independently reviewed in a randomized and blinded fashion by five multidisciplinary team members (three surgeons, two oncologists) and a treatment strategy determined. RESULTS: PET-CT changed the staging for ten patients (26%). This translated into a change in management decision for seven patients (18%). The concordance between individual management plans and treatment intent was 79% for CT (150 of 190 decisions) and it was 92% for PET-CT (175 of 190 decisions). Full concordance between multidisciplinary team members was 66% with CT staging and 74% with the addition of PET-CT. CONCLUSION: The use of PET-CT early in the staging algorithm for esophageal carcinoma altered the staging for a quarter of patients and the management for a fifth of patients, supporting its inclusion early in the staging algorithm.

Lymph nodes in the tail of the breast can be missed in standard axillary dissection.

AIMS: To determine whether excision of the tail of the breast usually by mastectomy or occasionally wide excision together with formal level 1 axillary node dissection (AND) for early breast cancer influences the quantity of harvested lymph nodes and the detection of axillary metastases. METHODS: Multiple regression and binary logistic regression analysis were performed on lymph node harvest data for level 1 AND performed prior to the adoption of sentinel node biopsy during a five year period from 1997 to 2001 at the Leicestershire Breast Unit, comparing AND with and without excision of the tail of the breast. RESULTS: One thousand six hundred and forty-eight level 1 ANDs were performed with a median node harvest of 14 (3-44). Multiple regression analysis identified that the total node harvest was increased by 1.03 nodes if the tail of the breast was excised (p<0.001) and this was independent of the effect on node count of node positivity. Operating surgeon and reporting pathologist did not influence node count. CONCLUSIONS: The results of this study indicate that low axillary nodes may be missed by AND without excision of the tail of the breast and support the use of targeted sentinel node biopsy that should identify an involved node at any site.

Inhibition of matrix metalloproteinase activity and growth of gastric adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro and murine models.

INTRODUCTION: Angiotensin converting enzyme (ACE) shares structural homology with the matrix metalloproteinase family of proteolytic enzymes (MMPs) responsible for degradation of the extracellular matrix (ECM). ACE inhibitors have been reported to protect against cancer in patients. The aim of this study was to determine whether the ACE inhibitor, captopril, could impair the activity of MMPs and impact on tumour invasion and growth in a cell line and murine model. METHODS: For proof of principle, the protein activity of human MMP-2 and MMP-9 produced by the HT1080 fibrosarcoma cell line was detected using gelatin zymography. Gene expression was determined by real time reverse transcriptase PCR and tumour cell invasion using Matrigel invasion chambers. The effect of captopril on the in vivo growth of MGLVA-1 human gastric adenocarcinoma xenografts was evaluated in a nude mouse model. RESULTS: Captopril inhibited activity of secreted MMP-9 and MMP-2, however, gene expression in HT1080 remained unaltered. Invasion of HT1080 cells was inhibited by 48% (p<0.001). Tumour size was reduced by 40-50% with 0.4 mg/ml captopril (p<0.01) and when combined with cisplatin the inhibition increased to 71% (p<0.05). DISCUSSION: ACE inhibitors inhibit the activity of secreted MMP-2 and -9 by a mechanism similar to synthetic MMP inhibitors. ACE inhibitors have previously been shown to inhibit tumour growth, however; this is the first study to demonstrate inhibition of a human gastric xenograft, both alone and in combination with cisplatin. These results support further investigation into the anticancer effects of ACE inhibitors.

Two-stage subtotal hepatectomy for metastatic adrenal adenocarcinoma, a case report.

Adrenal adenocarcinoma is a rare tumor with a poor prognosis. We present a case of recurrent adrenal adenocarcinoma with synchronous bilobar liver metastases that was treated by a two-stage subtotal hepatectomy. A formal right hemihepatectomy was performed with cryotherapy to a left lobe metastasis that was subsequently resected after a period of hepatic regeneration.

High light intensity: a critical factor in the wind-tunnel flight of two scarabs, the rose chafer and Japanese beetle.

We analyzed the flight of the rose chafer Macrodactylus subspinosus (F.) (Melolonthinae: Scarabaeidae) and the Japanese beetle Popillia japonica Newman (Rutelinae: Scarabaeidae) in a wind tunnel with controlled humidity, temperature, light, and airflow. The data indicate that an optimum combination of light and temperature dramatically improves their response to lures. Both species took off upwind, oriented to, and contacted the odor source well (40-60%) when light intensity was > 50% of a clear day, temperature was 26-27 degrees C, and relative humidity was 65-75%.

Development of an attractant for the scarab pest Macrodactylus subspinosus (Coleoptera: Scarabaeidae).

Field trials were conducted over several seasons to determine the attractant most successful in luring adult rose chafers, Macrodactylus subspinosus (F.), to traps. During the first season, 20 compounds were compared with the standard lure, valeric acid + hexanoic acid + octyl butyrate (1:1:1). The two new standards establishedthat season were: valeric acid + 1-nonanol (1:1); and valeric acid + hexanoic acid + octyl butyrate + 1-nonanol (1:1:1:1). The following season, 36 compounds were evaluated, comparing them to the new standards. The performance of the standard binary lure valeric acid + 1-nonanol was improved when the alcohol 1-nonanol was replaced by its analog trans-2-nonenol and this was confirmed during the third season. At the same time, a second test was conducted with 29 new candidates, which were combined with valeric acid and compared with the standard: valeric acid + hexanoic acid + octyl butyrate + 1-nonanol (1:1:1:1). A control and the single compound alpha-ionone were included, resulting in the discovery of a new more powerful attractant, alpha-ionone. Testing of alpha-ionone continued the following season, at which time the initial leading candidate and new ones containing trans-2-nonenol were tested against the single attractant alpha-ionone and various combinations of it. A new five-component mixture of valeric acid, hexanoic acid, octyl butyrate, trans-2-nonenol, and alpha-ionone out performed all other lure combinations.

Children's artistic responses to musical intervals.

In one experiment, White South African boys drew pictures in response to four musical intervals. In the second, the subjects were of both sexes and drawn from White, urban Black, and rural Black populations. Six intervals were used. Drawing content was similar cross-culturally. Consonances were perceived as generally positive; dissonances, generally negative. There was also an activity dimension. Children in a lower grade drew more concrete pictures than did those in a higher grade, regardless of age. Even young listeners were fairly consistent in their responses. This suggests that perception of musical meaning is a universal rather than culturally based phenomenon.

The neuropsychological significance of lateral preference for complex visual activities in children with learning disabilities.

In the present study the relationship between neuropsychological functioning and lateral preference for visual activities was examined with learning disordered children. Specifically, the relationship between measures of the Lateral Dominance Exam (LDE), scores on the Halstead-Reitan Neuropsychological Battery (HRNB), and the Wechsler Intelligence Scale for Children-Revised (WISC-R) were explored. A canonical analysis suggested that composites of neuropsychological functioning and lateral preference shared 22% of variance. Learning disabled children with strong right or left preference for visually guided motor activities showed lower performance in spatial tasks on the ipsilateral side and in simple motor skills on the contralateral side. Children in the present study with strong right preference patterns for visually assisted motor activities also showed low performance on visual tracking tasks. These data offer some support for assessing lateral preference in learning disabled children.

Neuropsychological subgroups of dementia of the Alzheimer's type.

Neuropsychological aspects of Dementia of the Alzheimer's Type (DAT) was considered using the scores from the Cambridge Cognitive Examination (CAMCOG) portion of the Cambridge Index of Mental Disorders in the Elderly (CAMDEX). CAMCOG scores for 51 DAT patients and 79 normal subjects were cluster analyzed. Results showed that the CAMCOG was effective in separating normal from demented subjects. The four subgroups of DAT patients differed more in "level" of impairment than for specific neuropsychological function. However, each level was characterized by losses in specific neuropsychological functions. Higher functioning groups exhibited greatest losses in memory skills, while the lowest functioning group showed greater loss of language skills.

The predictive validity of a neuropsychological screening measure.

This study examined the efficacy of a neuropsychological screening measure in discriminating between neurologically impaired and nonimpaired subjects. It also examined the ability of this screening measure correctly to classify impaired subjects according to right and left hemisphere involvement. The results showed that some 96% of subjects could be correctly classified as impaired or nonimpaired. The measure was also found correctly to identify the hemisphere involved in 95% of the impaired cases. The value and limitations of neuropsychological screening instruments was discussed in terms of portability and ease of administration.

The influence of topical corticosteroid therapy upon polymorphonuclear leukocyte distribution, vascular integrity and ascorbate levels in endotoxin-induced inflammation of the rabbit eye.

An acute inflammatory response was initiated in the rabbit eye by an intravitreal injection of bacterial endotoxin. We examined the effect of topical corticosteroid therapy upon polymorphonuclear leukocyte (PMN) infiltration into the eye, protein leakage into aqueous humor and ascorbate level in aqueous humor. Corticosteroid therapy initiated prior to injection of endotoxin suppresses the clinical signs of inflammation, partially prevents the fall in aqueous-humor ascorbate level, has little effect upon protein leakage, but markedly reduces PMN infiltration. Corticosteroid therapy initiated after the injection of endotoxin also suppresses the clinical signs of inflammation, reduces the fall in ascorbate levels and does not influence protein leakage. However, in this case there is a marked persistence of PMN infiltration into ocular tissues. Thus the number of PMNs present in the ocular tissues is little different from that in non-steroid treated control eyes, although the clinical signs of inflammation are reduced. We suggest that in the clinical situation, the initial anti-inflammatory activity of the corticosteroids is related to an inhibitory effect upon the activity of PMNs already within the tissues, which then prevents the ensuing cascade of characteristic inflammatory events.

A comparative study on the uptake of ascorbic acid by the iris-ciliary body of the rabbit, guinea pig and rat.

1. The uptake of 14C-ascorbic acid by the iris-ciliary body in vitro was examined in the rabbit, guinea pig and rat. 2. It was observed that iris-ciliary body from the rabbit and guinea pig, but not the rat, accumulated 14C-ascorbate to levels exceeding that in the bathing medium. 3. In all three species, the uptake of 14C-ascorbate was diminished by cold temperature; the degree of uptake at 0 degrees C was similar in the rabbit, guinea pig and rat iris-ciliary body. 4. Chromatographic examination of the 14C accumulated by the rabbit and guinea pig tissue demonstrated that the label remains almost exclusively as 14C-ascorbate.