Get the GIST? An overview of gastrointestinal stromal tumours.

GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract. The last 20 years have been revolutionary in the understanding of these tumours and began with the discovery of c-KIT, a proto oncogene that when mutated forms the molecular basis for the growth and development of these malignancies. Surgery was previously considered to be the only treatment modality in both local and advanced disease, however, the introduction of immunotherapy agents such as tyrosine kinase inhibitors has had profound effects on how we now approach and manage these tumours. These novel agents have significantly reduced the frequency of disease recurrence and dramatically improved survival, and serve as a model for the study of targeted therapies in other solid tumors. We present a review of gastrointestinal stromal tumours and consider the current evidence based detection and management of these unique tumors.

Gloveport hernioscopy.

It can be difficult to exclude occult, necrotic bowel in incarcerated herniae that reduce prior to emergent surgical exploration without resorting to further abdominal wall incisions. This case illustrates the Gloveport hernioscopy technique to identify necrotic small intestine that had spontaneously reduced in a man with a strangulated umbilical hernia. This minimally invasive technique allowed a multichannel examination of the peritoneal cavity without any further insult to the abdominal wall.

Unscheduled undergraduate teaching in surgery: a multi-institutional analysis.

A significant amount of valuable undergraduate medical teaching may be informal, unscheduled and delivered by non-consultant hospital doctors (NCHDs). 800 Questionnaires were distributed to consultants, NCHDs and medical students in Irish teaching hospitals. The aim was to quantify the level of unscheduled teaching carried out in these hospitals and the manner in which it was performed. The response rate was 46% (364/800). 71% of doctors who replied are independently teaching undergraduate medical students (77/109), including 71% of interns and senior house officers (48/68). Students tend to prefer small group teaching. Fifty-six percent of students suggest they would benefit from more surgical teaching time (144/255). No interns surveyed were scheduled to teach as part of a formal curriculum. A significant amount of unscheduled teaching by interns and senior house officers takes place in Irish hospitals. It may prove beneficial to incorporate interns into scheduled surgical teaching curricula.

An unusual cause of gastric outlet obstruction-incomplete annular pancreas.

Annular pancreas (AP) is a developmental disorder uncommonly suspected in adults. We report a case presenting with signs and symptoms of progressive gastric outlet obstruction. The diagnosis was suggested on pre-operative imaging and confirmed at laparotomy where the patient was successfully treated with a bypass procedure.

Massive hepatic cyst presenting as right-sided heart failure.

A 70-year-old woman presented with clinical features of right heart failure. Cardiopulmonary investigations included an echocardiogram, which showed a hepatic cyst compromising venous return and affecting right atrial filling and a CT abdomen showed a 15.5 × 11.5 cm-cystic mass involving the right hepatic lobe and compressing the right atrium. Percutaneous drainage of the cyst was performed. This led to complete resolution of symptoms but these recurred as the fluid re-accumulated. Subsequent definitive treatment with excision of the cyst was undertaken with symptomatic cure. This case is the first report of a hepatic cyst presenting as right heart due to compression of the right atrium.

Double trouble--duplication of the gallbladder requiring repeat laparoscopic cholecystectomy.

Duplication of the gallbladder is a surprisingly common phenomenon. Clinically, these patients present with straightforward gallbladder pathologies. It is a challenging preoperative diagnosis on ultrasound, and most cases are diagnosed intra-operatively. We present a case of gallbladder duplication, where the patient presented with biliary colic, had a straightforward laparoscopic cholecystectomy, and then represented with biliary colic four years later.

Adductor tenotomy in the management of groin pain in athletes.

This study evaluates the efficacy of adductor longus tenotomy in athletes with chronic tendinopathy refractory to conservative management. In a retrospective case series we report our experience with 109 male athletes who underwent unilateral adductor tenotomy during the period 2000-2005, all of whom responded to a detailed questionnaire. The criterion for tenotomy was chronic adductor origin pain which prevented training or playing (Level 4), limited training or playing (Level 3), or affected performance (Level 2)and which had failed to respond to conservative management including rest, rehabilitation and/or local steroid injection. Level 1 performance is classified as optimal performance with no pain. 99 of the 109 patients (91%) reported improvement. Best results were achieved in patients with maximum discomfort preoperatively (Level 4) with 32 of 38 (84%) patients returning to Level 1 performance. In conclusion, adductor tenotomy in athletes with severely incapacitating pain (Level 3/4) which fails to respond to conservative management offers the best opportunity of returning to competitive sport.

A comparison of performances of consultant surgeons, NCHDs and medical students in a modified HPAT examination.

Following the implementation of the Fottrell report, entry to medical school in Ireland has undergone significant change. Medical school studentship is now awarded based on a combination of points obtained from the final examination of Irish secondary schools (the leaving certificate) combined with HPAT scores (Health Professions Admissions Test). The HPAT is designed to test a candidate's knowledge in several different fields including problem solving skills, logical and non verbal reasoning. A sample HPAT was administered to a test group composed of consultant surgeons, non consultant hospital doctors, and medical students. Statistical analysis was performed and no significant difference was found between the performances of the groups. This is surprising as it was expected that groups with greater experience at medical problem solving would have translated to higher scores. This exposes a flaw within the HPAT system and a potential weakness in the process of doctor selection.

Pyogenic liver abscesses: diminished role for operative treatment.

BACKGROUND: Pyogenic liver abscess is a rare but potentially serious condition. It has traditionally been treated by open drainage; however interventional radiology is now becoming the standard of care. METHODS: All cases of liver abscesses admitted to a tertiary hospital over thirteen years (1995-2007) were retrospectively reviewed. Patient demographics, length of hospital stay, predisposing factors as well as cultured organisms were evaluated. Imaging techniques as well as patient management were also recorded. RESULTS: There were 66 hospital admissions of 61 patients with liver abscesses, 0.032% (66/205,079) of the total hospital admissions for the time period. Mean age was 61 years (range 26-90 years), male (36/61) 59%: female (25/61) 41%. Average hospital stay was 23 days (Range 1-84 days) and there were no deaths. 39 of 61 patients (64%) had a single abscess (90% right lobe). 20 of 61 patients (33%) had undergone a recent intra-abdominal procedure. Escherichia coli (10/61) and Enterococci (8/61) were the most frequent organisms isolated. Radiological intervention was performed in 50 of 61 (82%, 51% ultrasound and 31% CT guided). 9 of 61 (15%) were managed conservatively, while one case was managed surgically and another with endoscopic sphincterotomy and stent placement. CONCLUSIONS: Pyogenic liver abscesses are uncommon, and while associated with significant morbidity and prolonged hospital stay, mortality is now rare. Radiological intervention and anti-microbial therapy are the mainstay of treatment, and operative intervention is now rarely required.

Bone breaking strength and apparent metabolisability of calcium and phosphorus in selected and unselected broiler chicken genotypes.

1. The present study examined the bone strength and apparent mineral metabolisability of a selected broiler chicken compared with those of a relatively unselected genotype. 2. Selected (SB) and unselected genotypes (UB) were reared under standard conditions and were fed on either a high quality (HQ) or a low quality (LQ) diet. Tibiotarsi samples were collected at 42 d from SB and compared to tibiotarsi from UB of the same age and the same body mass (BM). 3. Bones were assessed for: bone breaking strength (BBS), morphology (weight and length), and both organic (OM) and inorganic content (ASH). Apparent dry matter digestibility and the coefficient of apparent metabolisability of calcium and phosphorus were determined at the same BM. 4. The BBS of SB (214 +/- 9 N) was greater than that of same-age UB (119 +/- 8 N) but the same as that of same-BM UB (218 +/- 10 N). At the same age, the SB had stronger, heavier bones with more ash and organic matter per unit length of tibiotarsus than UB. At the same BM, the tibiotarsi of the SB were shorter and lighter, with a higher ash and a similar organic content than the bones of the UB. At the same BM, BBS was about 15% lower in both genotypes fed on the LQ compared to the HQ diet. 5. The coefficients of apparent metabolisability of calcium and phosphorus were the same in both genotypes when fed on the HQ diet, but were lower in the SB than in the UB genotype when the birds were given the LQ diet. 6. The tibiotarsi of the selected broilers were stronger, or at least as strong, as those of the unselected broiler genotype, which may be due to similar levels of apparent calcium metabolisability of the selected chickens.

Neuromuscular stimulation causes muscle phenotype-dependent changes in the expression of the IGFs and their binding proteins in developing slow and fast muscle of chick embryos.

Insulin-like growth factor (IGF) -1 and -2 and binding protein (IGFBP-2, -4, and -5) expression can be affected by several environmental factors, but the impact of movement on the IGF axis during late embryogenesis has yet to be fully characterized. Movement was promoted in chick embryos during mid-embryogenesis using 4-aminopyridine (4-AP). The results indicate an increase in IGF-1 (P < 0.01) and a decrease in IGFBP-2 (P < 0.05) mRNA expression in slow muscle of the stimulated group compared with the control group. In fast muscle, there was a decrease in IGF-2 (P < 0.01) on embryonic day (ED) 16 and an increase in IGFBP-2 (P < 0.01) and IGFBP-4 (P < 0.05) and in IGFBP-5 (P < 0.05) expression on ED18 in the stimulated group compared with the control group. These results indicate that neuromuscular stimulation with 4-AP influences IGF axis gene expression in a muscle fiber type-dependent manner. Consequences of the changes in the IGF system for each muscle are discussed.

Net1 and Myeov: computationally identified mediators of gastric cancer.

Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.

Giant solitary non-parasitic cyst of the liver.

BACKGROUND: Cystic diseases of the liver and intrahepatic biliary tree are uncommon. The majority of cases are detected only when patients become symptomatic, or as an incidental finding on radiological imaging. METHODS: We discuss the case of a 25-yr-old female with a centrally located giant liver cyst causing obstructive jaundice, and briefly discuss the management options in the treatment of this uncommon problem. RESULTS AND CONCLUSIONS: Intervention is recommended in patients with symptomatic simple cysts of the liver. Surgical cystectomy is the treatment of choice for large deep seated cysts.

In ovo neuromuscular stimulation alters the skeletal muscle phenotype of the chick.

4-aminopyridine (4-AP) is a drug that blocks the potassium channels in neurons and stimulates the release of the neurotransmitter acetylcholine (ACh), enhancing its availability at the synaptic cleft. The effects of 4-AP induced neuromuscular stimulation on skeletal muscle formation and development were investigated in embryonic chicks. Fertile white Leghorn eggs were incubated at 37.5 degrees C and windowed on day three of incubation. On embryonic days (E) 10, 11, 12 and 13 half of the eggs were injected with 100 microl of PBS buffer containing 0.2 microg 4-AP and the control group was administered 100 microl of PBS only. 4-AP treated (T) embryos showed at least a 10% increase in mean body mass relative to the controls (C) (P<0.05) at ages E14, E15 and E16. Tibia and femur lengths in the 4-AP treated embryos were significantly greater than the controls at E15 and E16 (P<0.05). The 4-AP treated animals had a 36.8% greater number of myofibres than the control animals at E20. Nuclear number per cross sectional area in the M. Semitendinosus was significantly greater (P<0.01) at E16 in the treated compared to the control embryos. The 4-AP treated group exhibited a greater percentage area of oxidative fibres in cross sections of M. Semitendinosus than the control group at E16 (P<0.01) and at E20 (P<0.05). It may be concluded from these results that 4-AP induced neuromuscular stimulation has a significant effect on skeletal muscle characteristics, leg bone length and overall body mass.

Hepatic interleuklin 15 (IL-15) expression: implications for local NK/NKT cell homeostasis and development.

Interleukin 15 (IL-15) is critical for the development of human and murine natural killer (NK) cells and hepatic-derived NK T cells (NKT) in mice, and for the homeostatic maintenance of NK/NKT and CD8(+) memory T cells. The lymphocyte repertoire of an adult human liver includes significant populations of NK and NKT-like cells, which may arise locally from hepatic haematopoietic stem cells (HSCs). We investigated hepatic IL-15 levels and the expression of IL-2/IL-15-receptor beta-chain (IL-2/IL-15Rbeta; CD122) on mature hepatic lymphocytes and HSCs. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect secreted/intracellular IL-15 transcripts. IL-15 protein was localized using immunohistochemistry; levels were measured by enzyme-linked immunosorbent assay IL-2/IL-15Rbeta expression by flow-cytometry. Normal hepatic IL-15 protein was detected at 0.43 ng/100 mg total protein (n = 11, range 0.10 ng-0.9 ng). There was a significant increase in HCV-infected tissue (1.78 ng, P < 0.005, n = 11, range 0.18-2.43 ng). The staining pattern suggests that infiltrating monocytes and tissue resident Kupffer cells are the main producers. IL-15 protein was detected in supernatants from cultured liver biopsy specimens in the absence of stimulation (mean 175.8 pg/100 mg wet tissue, n = 3), which increased significantly upon stimulation (P < 0.05, mean 231.21 pg). On average, 61% of hepatic HSCs expressed IL-2/IL-15Rbeta suggesting a local lymphopoietic role. Eighty per cent of NK and 45.8% of CD56(+) T cells expressed IL-2/IL-15Rbeta, suggesting involvement in local CD56(+) cell activation and expansion. Constitutive expression of IL-15 protein and IL-2/IL-15Rbeta on hepatic lymphocytes suggests a key role in the generation and maintenance of the unique hepatic lymphoid repertoire. The significant increase observed in HCV-infected liver suggests a role for IL-15 in host antiviral responses in the liver.

Palliative stenting of recurrent malignancy at gastrojejunostomy anastomotic sites.

BACKGROUND: Surgical bypass procedures often provide excellent palliation in cases of malignant gastric outlet obstruction. Not uncommonly outlet obstruction can recur due to tumour involvement of the gastroenterostomy site. A further surgical procedure may not be feasible in these circumstances. AIMS: To report on the successful use of expandable metal stents in two such cases.

Genetic and phenotypic relationships between and within support and demand tissues in a single line of broiler chicken.

1. With commercial selection for increased broiler performance there has been a correlated increase in the incidence of several metabolic disorders. A study was undertaken to investigate the balance between the unselected support tissues (including the heart, liver, spleen and the components of the gastrointestinal tract (GIT)) which drive growth in the selected demand tissues (eviscerated body mass) by assessing the genetic correlations between these traits. 2. Data were collected on 483 broiler birds taken from a commercial male broiler line with pedigree information. 3. Genetic parameters were estimated by restricted maximum likelihood with an individual animal model. Heritability estimates for the production traits ranged between h2 = 0.48 and 0.59 for leg and breast mass, respectively. The support tissues were generally associated with low to moderate heritabilities ranging between h2 = 0.19 for proventriculus to h2 = 0.38 for duodenum mass, although moderately high heritability estimates (h2 = 0.51 to 0.54) were associated with the spleen and gizzard. 4. The genetic correlations between production traits and support organs were generally low, however, heart mass was positively correlated with all carcase components of the lean tissue mass; the genetic correlations ranged between r(g) = 0.55 with breast mass to r(g) = 0.64 with eviscerated body mass. 5. In general, there were strong positive genetic correlations between the different components of the GIT. Organs that have been implicated in the development of metabolic disorders such as ascites (for example, the heart) could theoretically be used in commercial selection indices due to moderate heritabilities (heart: h2 = 0.30) and favourable correlations with commercially important traits.