Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.

INTRODUCTION: MicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort. METHODS: The study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22. RESULTS: The total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002). CONCLUSION: The rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

Changing practices in the surgical management of hyperparathyroidism - a 10-year review.

AIM: Parathyroid surgery has undergone a paradigm shift over the last decade, with a move from traditional bilateral neck exploration to minimally invasive parathyroidectomy (MIP), and increasing reliance on pre- and intra-operative localization of overactive glands. We aimed to assess changing surgical practices and their impact on the management of parathyroid disease in a tertiary referral centre in the West of Ireland. METHODS: A retrospective cohort analysis of those patients undergoing a surgical intervention for parathyroid disease in the period between 1999 and 2009 in our centre was carried out. Data was analysed using PASW (v18) software. RESULTS: 248 procedures were performed, increasing from an annual rate of 6 in 1999 to 45 in 2009. 129 procedures were completed by minimally invasive means, following the introduction of MIP in 2003. Single-gland disease accounted for 87% of cases (n = 216) with carcinomas in 2 patients (0.8%). Pre-operative localization had disappointing diagnostic value, with high false negative rates for both ultrasound (37.3%) and Sestamibi Scanning (35.81%). Intra-operative adjuncts were more helpful, with intra-operative Parathyroid hormone monitoring facilitating curative resection of adenomas in 94.03% at 10 min. Median length of post-operative stay has significantly decreased from 6 days in 1999 to 1 night only in 2009 (p < 0.01, ANOVA). Those patients undergoing MIP had shorter stay than the open group (1.71 days -v-4.73, p = 0.003,t-test). CONCLUSION: The practice in our centre has shifted to a less invasive approach. Increased utilisation of intra-operative adjuncts has facilitated this change, and resulted in favourable changes in length of stay, extent of dissection, and number of patients treated.

The "flying" bile duct: avulsion of the common bile duct in a plane crash survivor.

Blunt trauma is an unusual cause of extrahepatic bile duct injury. This is a case of a 51-year-old gentleman who sustained a significant seatbelt injury in a plane crash. Laparotomy, performed due to persistent abdominal pain, revealed that the common bile duct (CBD) was completely avulsed from the duodenum. Following insertion of drains and transfer to a hepatobiliary centre, the devascularised CBD was excised and replaced with a roux-en-y hepaticojejunostomy. Necrotic tissue was debrided from the pancreatic head. A persistent bile leak developed from the sub-hepatic drain. Repeat laparotomy revealed a bile leak from small ducts on the liver surface. Ligation of the ducts and bioglue sealing of the area were successfully performed. Subsequent to this a pancreatic fistula developed from the main pancreatic duct, which has since resolved. This unusual case illustrates the need for prompt recognition and early repair to optimise outcomes in traumatic CBD injury.

Sestamibi scan-directed, minimally invasive video-assisted parathyroidectomy: an effective treatment for solitary parathyroid adenoma.

BACKGROUND: Solitary adenomas have been shown to be responsible for almost 90% of cases of primary hyperparathyroidism. AIM: The purpose of this study was to determine the utility of sestamibi scanning pre-operatively to guide minimally invasive video-assisted (MIVA) parathyroidectomy. METHODS: We reviewed 40 patients who underwent parathyroidectomy between 2003 and 2004. All patients underwent a pre-operative sestamibi scan. RESULTS: Thirty-three (82%) patients had a localized solitary adenoma on sestamibi scan. Of these patients 29 underwent attempted MIVA parathyroidectomy. MIVA parathyroidectomy was successful in 22 patients. When pre-operative sestamibi scanning was correlated with pathological diagnosis it was shown to have a sensitivity of 82% and positive predictive value of 94%. CONCLUSION: Pre-operative sestamibi scan localization of a parathyroid adenoma offers a 94% positive predictive value for adenoma location. This facilitates MIVA parathyroidectomy to be used effectively to treat primary hyperparathyroidism in the majority of patients.

Survival of ruptured abdominal aortic aneurysms in the west of Ireland: do prognostic indicators of outcome exist?

Ruptured abdominal aortic aneurysm (RAAA) is a demanding vascular surgical problem and the cause of significant morbidity and mortality. The aim of this study was to identify prognostic factors that influence outcome. Over 6 years, 42 ruptured abdominal aortic aneurysms were operated on with a mean diameter of 7.2 cm. RAAA was defined as free intraperitoneal rupture. Data were collected retrospectively from hospital medical records. The male: female ratio was 8:1 and the mean age was 74 years (range 55-89). Fifteen were in hypovolemic shock and 27 patients were clinically stable. The perioperative mortality rate for the 15 shocked patients was 60% (9 patients) and the 1-year cumulative survival rate was 33%. The perioperative mortality rate for the 27 clinically stable patients was 40% (11 patients) and the 1-year cumulative survival rate was 56%. Survival curves were constructed for these groups to compare male versus female, age >/= 70 versus age < 70, shocked versus stable, and preoperative hemoglobin (Hb) 10. No patient with preoperative cardiac arrest survived more than 24 hours. With VassarStats, the confidence interval for age, gender, hemodynamic status, and preoperative Hb were calculated. The standard weighted mean analysis by ANOVA gave a p value of < 0.001. The overall 30-day mortality rate was 47% (20 of 42) and the 1-year mortality rate was 52% (22 of 42). Male patients over 70 years with RAAA in hypovolemic shock with low Hb have a higher 30-day mortality rate and few survive more than 1 year. The study suggests that each of these 4 parameters separately was not a strong prognostic indicator. Collectively, however, they strongly influence the prognosis of patients with RAAA. These findings strengthen the case for selective treatment for RAAA.

Papillary carcinoma in a thyroglossal duct remnant--a review of thyroglossal surgery in a regional centre in the west of Ireland.

A review of thyroglossal duct remnants presenting to a regional centre in the West of Ireland was undertaken. Over a 15 yr period, 25 patients were operated on for duct remnants. The mean age was 19.6 yr and ranged from 3 to 68 yr. There were 16 (64 per cent) males and 9 (36 per cent) females. Seventeen (68 per cent) patients were less than 20 years at the time of surgery. Four patients presented with a sinus and the remainder with a cystic lesion. Two patients experienced recurrent disease. One patient, a 41 yr old female, had a papillary carcinoma of a thyroglossal cyst. There were no clinical features distinguishing this patient from those with benign cystic remnants of the thyroglossal duct. The possibility of carcinoma in older patients, in particular females, presenting with thyroglossal cysts emphasises the importance of performing a formal Sistrunk's operation. It reduces the risk of recurrence of the cyst and may reduce the risk of recurrence of the tumour as the duct may provide a route for the spread of tumour.

Analgesia following appendicectomy--the value of peritoneal bupivacaine.

PURPOSE: Peritoneal inflammation is an important feature in many patients presenting with appendicitis. The contribution of peritoneal nerve fibres to pain experienced after appendicectomy has received little attention. METHOD: In this prospective double blind randomized study a consecutive series of 60 patients undergoing appendicectomy for suspected appendicitis were enrolled. A dose of 1.5 mg.kg-1 bupivacaine 0.5% was used. Group one patients received the entire dose of bupivacaine subcutaneously. Group two patients received half the dose subcutaneously (s.c.) and half the dose to the peritoneum. Pain scores were assessed pre-operatively and at 30 min, 12 and 24 hr post-operatively using a visual analogue scale. Time to first analgesia and total analgesia requirements in the first 24 hr were recorded. RESULTS: The patients receiving the s.c. combined with peritoneal bupivacaine had a lower pain score 30 min post-operatively (32 +/- 2 vs 54 +/- 4; P < 0.0001), a longer time to first analgesia (248 +/- 20 vs 164 +/- 17 min; P = 0.002) as well as lower opioid (68 +/- 5 vs 100 +/- 7 mg; P = 0.0002) and non steroidal analgesic requirements (65 +/- 6 vs 96 +/- 6 mg; P = 0.007) in the first 24 hr post-operatively. CONCLUSION: A combination of s.c. and peritoneal infiltration with bupivacaine is superior to skin infiltration alone in the relief of pain post appendicectomy.

Swan Ganz catheter--all in a knot.

In this case report an unusual complication is described following insertion of a Swan Ganz catheter. A 79-year-old male patient experienced knotting of the catheter. Methods of avoiding this problem and removal of a knotted catheter are discussed.

Thyroid disease in the west of Ireland: an atypical incidence of neoplasia.

This study was established to review the spectrum of thyroid disease presenting to a regional centre in the West of Ireland. Over a ten year period 414 thyroidectomies were performed. The most common histological diagnosis was nodular goitre (238 patients). There were 134 thyroid neoplasms; 87 (65%) adenomas, 40 (30%) carcinomas and 7 (5%) lymphomas. A breakdown of the cancers revealed 17 (36%) papillary and 14 (30%) follicular carcinomas with 7 (15%) lymphomas. Six (13%) patients presented with anaplastic tumors. Solitary nodules had a high cancer risk (25%) in comparison with multinodular or diffuse goitres (5%). Thyroiditis accounted for 38 cases while only 10 thyroidectomies were performed for Graves' disease.

Escaped faecalith causing a persistent psoas abscess.

Faecaliths have been widely implicated in the aetiology of acute appendicitis. According to Shaw, stones are formed in the appendix with greater frequency than in either the gall bladder or the urinary tract. In spite of this, faecaliths appear to cause few complications outside the appendix. We report an unusual complication resulting from an escaped appendiceal faecalith.

Increased DNA-bending activity and higher affinity DNA binding of high mobility group protein HMG-1 prepared without acids.

Recently, DNA ring closure assays showed that high mobility group protein HMG-1 and its close homolog HMG-2 mediate sequence-independent DNA flexion. This DNA-bending activity appears to be central to at least some of the recently elucidated functions of HMG-1/2, such as the enhancement of progesterone receptor DNA binding. Here we show that standard purification procedures utilizing perchloric and trichloroacetic acid can produce HMG-1 significantly deficient in its abilities to bind and bend double-stranded DNA, while acid-independent methods purify HMG-1 that is superior in these respects. Significant losses of DNA ring closure activity were seen upon limited 2-5-h exposures of nonacid-purified HMG-1/2 to perchloric acid and/or trichloroacetic acid. Measurements of the apparent DNA dissociation binding constant (Kd(app)) of acid-extracted preparations of HMG-1 gave a wide range of values, and only those preparations demonstrating little DNA ring closure activity had Kd values near the previously published value (approximately 10(-6) M). The highest ring closure activities and lowest Kd(app) (< 3 x 10(-9) M) were obtained for HMG-1 purified without acids. These combined results support the use of alternative, non-acid purification procedures for preserving the DNA-bending activity of HMG-1/2 and suggest that past procedures utilizing acids have led to an underestimation of the affinity of HMG-1 for DNA.

Duodenal rupture with avulsion of the bile duct: an unusual injury.

Blunt abdominal trauma may give rise to infrequent and unusual patterns of organ damage requiring prompt and complete exploratory laparotomy if the full extent of injury is to be recognised. We present a case of avulsion of the common bile duct in association with duodenal rupture to illustrate the importance of this strategy.

Ultrasonic screening for the detection of abdominal aortic aneurysms.

Detection of aortic aneurysms before they rupture is imperative if the mortality rate from this disease is to be reduced. Although large aneurysms frequently are palpable, small aneurysms--especially in obese patients--are seldom recognized on physical examination. Ultrasound, which is noninvasive, relatively inexpensive, and nearly 100 per cent accurate in identifying the presence or absence of aneurysms, is well suited to screening. In high-risk populations (patients over the age of 50 with coronary artery or peripheral vascular disease), ultrasonic screening is probably cost-effective.

Carotid stump syndrome: a colour-coded Doppler flow study.

Colour-coded Doppler flow imaging (angiodynography) was performed on 29 patients with 30 internal carotid artery occlusions. Large internal carotid stumps were revealed as intravascular cul-de-sacs demonstrating vortices of blue flow reversal. Large carotid stumps or significant external carotid stenoses were present in nine patients (9 arteries). Such patients were significantly more likely to develop symptoms of cerebral ischaemia during follow up which averaged 18 months (P = 0.016; Fisher exact). These results support the concept of embolisation from the carotid bifurcation (residual stump or external stenosis) as a cause of episodic cerebral ischaemia following internal carotid occlusion. Angiodynography may prove to be a useful tool for selecting appropriate patients for treatment.

Radionuclide ventriculography and two dimensional echocardiography as predictors of left ventricular performance during aortic vascular surgery.

Sixteen consecutive patients scheduled for elective aortic vascular surgery underwent preoperative LVEF determination employing two dimensional echocardiography (2DE) and radionuclide ventriculography (RNV). Measured and derived indices of cardiac function were recorded before and after induction of anaesthesia, aortic cross-clamping and aortic unclamping. Induction of anaesthesia was associated with significant decreases in mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and with a highly significant decrease in left ventricular stroke work index (LVSWI). Aortic cross-clamping was associated with significant increases in MAP and systemic vascular resistance (SVR) whereas aortic unclamping was associated with a significant decrease in SVR. Preoperative LVEF, as measured by RNV and 2DE, were similar. Resting ejection fractions correlated poorly with both preoperative cardiac indices and with changes in indices of left ventricular performance seen intraoperatively. Preoperative ejection fraction determination did not predict intraoperative left ventricular performance. Preoperative exercise scanning may prove more informative.

High fibre diet in symptomatic diverticular disease of the colon.

Over the past decade fibre supplementation has achieved widespread acceptance in the management of symptomatic diverticular disease, although the efficacy of this treatment has been debated. We have conducted a retrospective review of 72 patients admitted to hospital with symptomatic diverticular disease over a ten year period in order to determine whether or not high fibre diet afforded protection against the development of complications, necessity for surgery or persistence of symptoms. Fifty-six patients were treated non-operatively, of these 43 received advice concerning a high fibre diet but only 31 patients complied. The 12 patients who failed to take additional fibre and the 13 patients who never received dietary advice (25 patients) formed the non high fibre group. Those treated with fibre supplementation fared significantly better in developing fewer complications and required less surgery (P less than 0.05). At the time of follow-up review patients on a high fibre diet reported significantly fewer symptoms (P less than 0.05).