The increasing burden of the 2-week wait colorectal cancer pathway in a single centre: the impact of faecal immunochemical tests.

INTRODUCTION: Two-week wait (TWW) volume and colorectal cancer (CRC) detection pose an increasing challenge for NHS cancer services. Primary aims were to assess the introduction of faecal immunochemical tests (FIT) into clinical practice at our centre, the impact on TWW referral volume and CRC diagnoses, and to provide an update to previously published work. A secondary aim was to correlate FIT value and investigation. METHODS: TWW CRC data following incorporation of FIT into clinical practice were analysed (1 June 2019-31 July 2021). Parameters assessed were monthly referral volume, CRC detection, primary care FIT volume and secondary care investigations. Referrals and CRC detection rates were compared with previously published data (2009-2019). Data relating to primary care FIT were collated from Berkshire and Surrey Pathology Services. RESULTS: TWW referrals increased 360% (2009-2020). CRC incidence decreased from 8.87% to 3.24%. Following incorporation into clinical practice, primary care FIT requests have increased to >450/month and accompanied 1,722/4,796 referrals. CRC incidence is static (3-4%). Patients with FIT <10µg Hb/g faeces undergo radiological imaging more commonly, whereas FIT-positive patients are more likely to undergo endoscopy, although the difference is not statistically significant. CONCLUSIONS: No significant change in CRC diagnosis was observed, despite increasing TWW referrals. Increasing utilisation of FIT in both primary and secondary care has helped maintain CRC detection while avoiding diagnostic delay. This study supports growing evidence highlighting the value of FIT in triage, referral and TWW investigation. FIT appears increasingly important for allocating secondary care resources (endoscopy), while guiding primary care referral. Additional low-cost strategies to determine prioritisation or reassurance (e.g. repeat FIT) require further evaluation.

Gastric outlet obstruction secondary to a wandering spleen: systematic review and surgical management of a case.

INTRODUCTION: A wandering spleen occurs when laxity or absence of the suspensory ligaments allows migration throughout the abdomen. Gastric outlet obstruction resulting from this abnormality is rare. We present a systematic literature search and a case that was managed successfully with surgical intervention at our centre. METHODS: A systematic search of the PubMed, Embase™, Medline® and Google Scholar™ databases was carried out employing the combined search terms "gastric outlet obstruction" AND "wandering spleen". Six results were included for final analysis. RESULTS: All six search results described a single case each. Patients underwent surgical management (open or laparoscopic) after initial investigation utilising a range of modalities. There were no mortalities reported at 90 days. The single case we present was complicated by gastric perforation; the patient made a successful recovery following open splenopexy and stapled wedge resection of the stomach. CONCLUSIONS: A wandering spleen is a rare diagnosis and there are only six reported cases of gastric outlet obstruction secondary to a wandering spleen in the literature. None report associated gastric perforation. There are a variety of presenting symptoms, intraoperative findings and operative techniques used to address the gastrosplenic abnormality. The case reported by our centre adds to this limited evidence base and demonstrates a successful outcome from definitive surgical management. We highlight the need to seek early gastro-oesophageal expertise if any gastric pathology is found together with anatomical abnormality of the spleen.

Do food and stress biomarkers work for wastewater-based epidemiology? A critical evaluation.

Dietary characteristics and oxidative stress are closely linked to the wellbeing of individuals. In recent years, various urinary biomarkers of food and oxidative stress have been proposed for use in wastewater-based epidemiology (WBE), in efforts to objectively monitor the food consumed and the oxidative stress experienced by individuals in a wastewater catchment. However, it is not clear whether such biomarkers are suitable for wastewater-based epidemiology. This study presents a suite of 30 urinary food and oxidative stress biomarkers and evaluates their applicability for WBE studies. This includes 22 biomarkers which were not previously considered for WBE studies. Daily per capita loads of biomarkers were measured from 57 wastewater influent samples from nine Australian catchments. Stability of biomarkers were assessed using laboratory scale sewer reactors. Biomarkers of consumption of vitamin B2, vitamin B3 and fibre, as well as a component of citrus had per capita loads in line with reported literature values despite susceptibility of degradation in sewer reactors. Consumption biomarkers of red meat, fish, fruit, other vitamins and biomarkers of stress had per capita values inconsistent with literature findings, and/or degraded rapidly in sewer reactors, indicating that they are unsuitable for use as WBE biomarkers in the traditional quantitative sense. This study serves to communicate the suitability of food and oxidative stress biomarkers for future WBE research.

Does intra-operative flexible endoscopy reduce anastomotic complications following left-sided colonic resections? A systematic review and meta-analysis.

AIM: Postoperative anastomotic leakage (AL) or bleeding (AB) significantly impacts on patient outcome following colorectal resection. To minimize such complications, surgeons can utilize different techniques perioperatively to assess anastomotic integrity. We aim to assess published anastomotic complication rates following left-sided colonic resection, comparing the use of intra-operative flexible endoscopy (FE) against conventional tests used to assess anastomotic integrity. METHODS: PubMed/MEDLINE and Embase online databases were searched for non-randomized and randomized case-control studies that investigated postoperative AL and/or AB rates in left-sided colonic resections, comparing intra-operative FE against conventional tests. Data from eligible studies were pooled, and a meta-analysis using Review Manager 5.3 software was performed to assess for differences in AL and AB rates. RESULTS: Data from six studies were analysed to assess the impact of FE on postoperative AL and AB rates (1084 and 751 patients respectively). Use of FE was associated with reduced postoperative AL and AB rates, from 6.9% to 3.5% and 5.8% to 2.4% respectively. Odds ratios favoured intra-operative FE: 0.37 (95% CI 0.21-0.68, P = 0.001) for AL and 0.35 (95% CI 0.15-0.82, P = 0.02) for AB. CONCLUSION: This meta-analysis showed that the use of intra-operative FE is associated with a reduced rate of postoperative AL and AB, compared to conventional anastomotic testing methods.

Laparoscopic Common Bile Duct Exploration for Retrieval of Impacted Dormia Basket following Endoscopic Retrograde Cholangiopancreatography with Mechanical Failure: Case Report with Literature Review.

Dormia baskets are commonly used during endoscopic retrograde cholangiopancreatography (ERCP). One complication is basket retention, through impaction with a gallstone or wire fracture. We describe a case where the external handle of the basket snapped causing retained basket plus large gallstone impacted in the common bile duct (CBD). Following laparoscopic cholecystectomy, laparoscopic CBD exploration allowed direct stone fragmentation under vision with the choledochoscope. Fragments were removed using a choledochoscopic basket and Fogarty catheter, and the basket was withdrawn. Literature search identified 114 cases of retained baskets with management including shockwave lithotripsy (27%), papillary balloon dilatation (22%), open CBD exploration (11%), and one laparoscopic case.

A survey of doctors at a UK teaching hospital to assess understanding of recent changes to consent law.

BACKGROUND: The UK Supreme Court recently ruled that when consenting patients for treatments or procedures, clinicians must also discuss any associated material risks. We surveyed medical staff at a large UK teaching hospital in order to ascertain knowledge of consent law and current understanding of this change. MATERIALS AND METHODS: Email survey sent to medical staff in all specialities at Norfolk and Norwich University Hospital in February 2016. RESULTS: 245 responses (141 Consultants and 104 junior doctors, response rate 32%). 82% consent patients for procedures at least monthly and 23% daily. 31% were not familiar with the concept of material risk. 35% were familiar with the recent change in consent law, 41% were not. 18% were "very uncertain" and 64% "a little uncertain" that their consenting process meets current legal requirements. >92% think that landmark cases and changes in law should be discussed through professional bodies and circulated better locally. CONCLUSION: The majority were not familiar with the concept of material risk and recent legal changes. A majority were not confident that their practice meets current requirements, suggesting that recent changes in consent law may not be widely understood at this hospital. We suggest more guidance and education may be necessary than is currently available. Increased understanding of recent changes to consent law will reduce the risk taken by NHS trusts and offer patients a service compliant with Supreme Court guidance.

Assessing the effect of increasing injection activity for myocardial perfusion imaging in overweight patients.

In our previous publication, we proposed to increase the injection activity for overweight patients. We have now implemented this for our patients, i.e. increasing the activity for patients above 99 kg. In the present study, we audited whether this increased activity for overweight patients improved the myocardial counts effectively and also whether it improved the image quality for these patients. 125 consecutive normal myocardial perfusion studies were included into the study. The total left ventricular myocardial count was calculated, as was the total left ventricular myocardial volume using the Cedar Sinai QPS program. The myocardial count per millilitre of the myocardium (c ml(-1)) was correlated with patient weight using regression analysis. There was no significant difference (p = 0.120) among the mean myocardial counts for patients over 99 kg (n = 40, 1548 c ml(-1)) compared with patients in the 70-79 kg range (n = 26, 1746 c ml(-1)). This indicates that the previously proposed algorithm for adjusting injection activity maintains the count density in the myocardium and should be used for all patients over 99 kg. There was, however, a significant steady decrease with increased weight in the myocardial counts for patients under 100 kg (p<0.001), a range in which injection activity was not adjusted for weight. To correct for this, we now propose that the injection activity should be adjusted for all patients over 80 kg, using the previously proposed algorithm.

Current induction in a fiberglass guidewire compared to conventional wires during simulated papillotomy.

BACKGROUND: Current induced in a guidewire during papillotomy poses a danger of injury to the bile duct. We measured currents induced in three commercially available guidewires and a prototype fiberglass wire during simulated sphincterotomy under standard and nonstandard conditions. METHODS: Blended current at 55 W was applied to a double-lumen papillotome grounded through a 1000 omega resistor. For extreme conditions, power was increased to 70 W using a single-lumen papillotome. Fault conditions were created with a break in the insulation at the distal end of each wire. Guidewire-induced current was measured, and safety calculations performed for adherence to accepted standards for electrosurgical devices. RESULTS: Induced current was within safety limits for all wires tested under standard conditions. With insulation faults, one of the commercially available wires was unsafe. Under extreme conditions, with or without faults, the three commercial wires produced currents ranging from 9% to 225% above acceptable levels, while only the prototype wire remained safe. CONCLUSIONS: Most guidewires contain metal cores that function as capacitors. Because its core is primarily fiberglass, the prototype wire generates less induced current under nonstandard conditions, thus achieving a greater margin of safety during wire-guided sphincterotomy.

Effects of internal mammary artery dissection on phrenic nerve perfusion and function.

The effects of left internal mammary artery (LIMA) dissection and distal division on phrenic nerve perfusion and function were examined in an adult swine model. Phrenic nerve perfusion was determined by left atrial injection of radioactively labeled microspheres. Phrenic nerve function was determined by measuring nerve and diaphragm potentials evoked by bilateral phrenic nerve stimulation. In the first group of animals (n = 9), the LIMA was dissected with ligation of all its branches. Left phrenic nerve perfusion and function decreased after LIMA dissection in every animal studied, whereas only minimal changes were observed on the right. Sixty minutes after LIMA dissection, left phrenic nerve mean perfusion decreased 71%. Left phrenic nerve and left diaphragm mean action potential amplitudes decreased 54% and 80%, respectively. In the second group of animals (n = 4), the LIMA dissection was performed without division of the pericardiacophrenic artery, a small proximal branch of the internal mammary artery that supplies the phrenic nerve. Sixty minutes after LIMA dissection, left phrenic nerve perfusion had decreased by 21% from control values, with a corresponding decrease in left phrenic nerve and diaphragm mean action potential amplitudes of 19% and 23%, respectively. These results indicate that LIMA dissection with division of all its branches in this model is associated with a significant impairment in left phrenic nerve perfusion and function and suggests a causal relationship. These results may also explain the apparent increased phrenic nerve cold sensitivity and increased incidence of phrenic nerve dysfunction associated with LIMA grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of octopamine and synephrine stereoisomers on alpha-adrenoceptors.

1. The activities of the (-)- and (+)-forms of m- and p-octopamine and m- and p-synephrine on alpha 1-adrenoceptors from rat aorta and anococcygeus and alpha 2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA). 2. The rank order of potency of the (-)-forms on alpha 1-adrenoceptors from rat aorta and alpha 2-adrenoceptors was NA greater than m-octopamine = m-synephrine greater than p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on alpha 1-adrenoceptors from rat aorta and 150 fold less active on alpha 2-adrenoceptors. The two p- compounds were 1,000 fold less active than NA on both alpha 1-adrenoceptors from rat aorta and alpha 2-adrenoceptors. The rank order of potency of the (-)- forms on alpha 1-adrenoceptors from rat anococcygeus was NA = m-synephrine greater than m-octopamine greater than p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (-)-m-synephrine. The two p- compounds were 30 fold less active than NA. 3. The rank order of potency of the (+)- forms was NA greater than m-octopamine greater than m-synephrine greater than p-octopamine greater than p-synephrine on both alpha 1- and alpha 2-adrenoceptors. The potency of each (+)- form was 1-2 orders of magnitude less than that of the (-) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both alpha 1- and alpha 2-adrenoceptors. 4. The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (-)-NA and (-)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for alpha-adrenoceptor subtypes, it is concluded that the rat aorta contains only alpha 1-adrenoceptors while the rabbit saphenous vein possesses predominantly alpha 2-adrenoceptors. 5. Ligand binding data for the octopamine and synephrine stereoisomers at alpha 1- and alpha 2-binding sites from rat cerebral cortex was also obtained. (-)-Forms were more active than (+)-forms. The rank order of affinity of the (-)-forms for both alpha 1- and alpha 2-binding sites was NA greater than m-octopamine = m-synephrine greater than p-synephrine greater than p-octopamine. The relative affinities of the members of the series against alpha 1-binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m- and p-compounds relative to that of ( -)-NA were much greater at the x2-binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (-)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6. The activities of m-octopamine and m-synephrine were not significantly different from each other on either a,-adrenoceptors from rat aorta or x2-adrenoceptors; however, m-synephrine is more active than m-octopamine on a,-adrenoceptors from rat anococcygeus. Both m-octopamine and msynephrine can be considered to be naturally occurring x,-selective amines. However, if m- and poctopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on m,- and x2-adrenoceptors are too low to be physiologically significant.

Blockade by nifedipine of responses to intravenous bolus injection or infusion of alpha 1- and alpha 2-adrenoceptor agonists in the pithed rat.

Nifedipine was tested against pressor responses in the pithed rat to ten agonists with varying selectivity for alpha 1- and alpha 2-adrenoceptors, injected as a bolus or infused intravenously: i.e. amidephrine, azepexole, cirazoline, indanidine, M7, methoxamine, noradrenaline (NA), oxymetazoline, phenylephrine and xylazine. Nifedipine, administered before the agonists, inhibited responses initiated by all agonists, usually for both the bolus and infusion responses. With a bolus, blockade was significantly greater against the more prolonged, secondary components of the pressor responses. This demonstrates that calcium-entry occurs during the secondary component of the alpha-adrenoceptor-mediated response and can be initiated by either alpha 1- or alpha 2-adrenoceptor subtypes. The time courses of responses to infusion varied. Selective alpha 1-adrenoceptor agonists, with the exception of indanidine, did not produce a stable pressor response during the 20 min infusion time but alpha 2-adrenoceptor agonists did. Nifedipine reduced responses to infusion with no preference for alpha 1- or alpha 2-agonists. Phenylephrine and NA produced pressor responses which reached a peak and then declined during the remainder of the infusion. The levels of NA in arterial and venous plasma were measured by h.p.l.c. during the infusion of NA. Arterial NA levels rose throughout the infusion whereas venous levels remained relatively unaffected. The absolute levels of plasma NA suggest that a large proportion of intravenously administered NA is removed in the pulmonary circulation and the remainder is removed in the systemic circulation with negligible recirculation. The consequences of these results, for assessment of the mechanisms of action of adrenoceptor agonists and calcium entry blockers, are discussed.

The influence of blood gases on alpha 1- and alpha 2- adrenoceptor-mediated pressor responses in the pithed rat.

The influence of blood gases on alpha 1- and alpha 2-adrenoceptor-mediated pressor responses was studied in the pithed rat by varying the inspired gas mixture or the ventilation stroke volume. Acidosis favoured the peak responses to the alpha 2-adrenoceptor agonist, xylazine, while alkalosis favoured the peak responses to the alpha 1-adrenoceptor agonist, phenylephrine. A combination of hypoxia and hypercapnia greatly depressed the alpha 1 response to phenylephrine whereas the alpha 2 response to xylazine remained relatively unaffected. When Pao2 was varied in either acidotic or alkalotic conditions the response to the phenylephrine increased as Pao2 increased. To prevent hypoxia in air ventilated rats, large stroke volumes were required. This caused alkalosis and hence decreased responsiveness to xylazine. Consequently, air ventilated pithed rats gave poorer responses to xylazine than did those ventilated on 100% O2. The results show that alpha 1- and alpha 2-adrenoceptor-mediated pressor responses can be differentially affected by blood gases. The relative contribution of alpha 1- and alpha 2-adrenoceptors to vascular tone may be either under- or over-estimated depending on the arterial blood gases.

Influence of blood gases, Ca2+-entry blockade and angiotensin converting enzyme inhibition on pressor responses to alpha-adrenoceptor agonists: evidence in vivo for subtypes of response independent of receptor subtype?

The pressor responses in the pithed rat to alpha-adrenoceptor agonists can be modified by alterations in arterial blood gas levels or by drugs which interfere with excitation-contraction coupling processes in the vascular smooth muscle, e.g. Ca2+-entry blockers or angiotensin converting enzyme (ACE) inhibitors. However, the extent of these influences depends on which agonist is used. The pressor response to intravenous injection of alpha-adrenoceptor agonists consists of two phases: an initial rapid but transient response (phase I) is followed by a response of slower onset but longer duration (phase II). We have examined the effects of manipulation of arterial blood gases, a Ca2+-entry blocker, nifedipine, and an ACE inhibitor, teprotide, on the pressor responses to a series of alpha-adrenoceptor agonists. In each case, the effects showed selectivity for one or other of the two phases and the differences in susceptibility between agonists could be explained by the relative sizes of the two phases in their responses. In general, phase II was more susceptible to alkalosis, nifedipine and teprotide, so that drugs in which this component predominated were more susceptible to these factors. In contrast there was no direct correlation with the receptor subtypes activated by the agonists.