Oesophagopleural fistula after pneumonectomy: A systematic review and case series.

INTRODUCTION: There is a paucity of data on the optimal management of oesophagopleural fistula (OPF) following pneumonectomy. The current published literature is limited to case reports and small case series. Although rare, OPF can have a significant impact on both the morbidity and mortality of patients. METHODS: Two cases of OPF managed at our institution were reported. A systematic review was then conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance concerning OPF following pneumonectomy. Demographic, operative and management data were analysed. FINDINGS: Systematic review-identified data pertaining to 59 patients from 31 papers was collated. Median patient age was 59.5 years with pneumonectomy performed typically for malignancy (68%) or tuberculosis (19%). Median time from pneumonectomy to a diagnosis of OPF was 12.5 months. Twenty-five per cent of the patients had a synchronous bronchopleural fistula. Management of OPF in this setting is heterogenous. Conservative management was often reserved for asymptomatic or unfit patients. The remainder underwent endoscopic or surgical correction of the fistulae or a combination of the two with varying outcomes. Median follow-up was 18 months. All-cause mortality was 31% (18/59) with a median duration from pneumonectomy to death of 35 days (range 1-1,095). CONCLUSIONS: Major heterogeneity of management for this rare complication hinders the introduction of standardised guidance of post-pneumonectomy OPF. Surgical and endoscopic intervention is feasible and can be successful in specialist centres. Adopting an multidisciplinary team approach involving both oesophagogastric and thoracic surgery teams and the introduction of a registry database of postoperative complications are likely to yield optimal outcomes.

Surgical training during the COVID-19 pandemic at a designated 'cold' site: are we meeting the challenge?

INTRODUCTION: There has been a marked reduction in surgical operative training opportunities during the COVID-19 pandemic. This may be improved by the establishment of 'cold' sites for NHS elective surgery. We investigated the training opportunities at a newly designated elective surgery cold site in the West Midlands, UK. METHODS: An observational retrospective study was undertaken to include all gastrointestinal and urological elective surgery at a single 'cold' site during the first peak of the COVID-19 pandemic. Patient demographics, details of surgery and data relating to surgical training such as primary surgeon and portfolio index procedure were collected. Factors affecting the likelihood of trainees being the primary surgeon were analysed using logistic regression models. RESULTS: There were 880 patients, with a median (interquartile range) age of 62 (48-74). Some 658 (74.8%) procedures were defined as 'index procedures' for specialty training year 4 (ST4) level: 409/509 (80.4%) for urology, 155/235 (66%) for colorectal and 94/136 (69.1%) for upper gastrointestinal (GI). Only 253/880 (28.8%) procedures were performed by a trainee as the primary surgeon: 201/509 (39.4%) for urology, 21/235 (8.9%) for colorectal and 31/136 (22.8%) for upper GI. The likelihood of a trainee being the primary surgeon was reduced for major surgery (p<0.001) and for GI surgery when compared with urology (p<0.001). CONCLUSIONS: Surgical training was facilitated at an elective surgery 'cold' site during the COVID-19 pandemic, but at lower levels than anticipated. Type of surgery influenced trainee participation. Surgical training should be incorporated into 'cold' site elective surgical services if trainees are to be prepared for the future.

Does declared surgeon specialist interest influence the outcome of emergency laparotomy?

INTRODUCTION: In the UK, general surgeons must demonstrate competency in emergency general surgery before obtaining a certificate of completion of training. Subsequently, many consultants develop focused elective specialist interests which may not mirror the breadth of procedures encountered during emergency practice. Recent National Emergency Laparotomy Audit analysis found that declared surgeon special interest impacted emergency laparotomy outcomes, which has implications for emergency general surgery service configuration. We sought to establish whether local declared surgeon special interest impacts emergency laparotomy outcomes. METHODS: Adult patients having emergency laparotomy were identified from our prospective National Emergency Laparotomy Audit database from May 2016 to May 2019 and categorised as colorectal or oesophagogastric according to operative procedure. Outcomes included 30-day mortality, return to theatre and length of stay. Binomial logistic regression was used to identify any association between declared consultant specialist interest and outcomes. RESULTS: Of 600 laparotomies, 358 (58.6%) were classifiable as specialist procedures: 287 (80%) colorectal and 71 (20%) oesophagogastric. Discordance between declared specialty and operation undertaken occurred in 25% of procedures. For colorectal emergency laparotomy, there was an increased risk of 30-day mortality when performed by a non-colorectal consultant (unadjusted odds ratio 2.34; 95% confidence interval 1.10-5.00; p = 0.003); however, when adjusted for confounders within multivariate analysis declared surgeon specialty had no impact on mortality, return to theatre or length of stay. CONCLUSION: Surgeon-declared specialty does not impact emergency laparotomy outcomes in this cohort of undifferentiated emergency laparotomies. This may reflect the on-call structure at Birmingham Heartlands Hospital, where a colorectal and oesophagogastric consultant are paired on call and provide cross-cover when needed.

Supplemental protein and postnatal growth of very low birth weight infants: a randomized trial.

BACKGROUND: Providing adequate nutritional support to promote optimal postnatal growth for very low birth weight (VLBW) infants has been a difficult problem to surmount in the NICU. During the past 4 decades, improvements in neonatal critical care have made it possible for more VLBW infants to survive to discharge from NICUs. The NICHD Neonatal Network reported that while intrauterine growth restriction was present in 22% of VLBW infants at birth, 91% demonstrated postnatal growth restriction by 36 weeks post menstrual age. The persistence of this nearly universal growth deficit is associated with the inadequacy of protein and energy intake, which may account for 45-50% of the postnatal growth restriction. OBJECTIVE: The purpose of this study was to assess whether increasing enteral intake, using supplemental protein, would improve postnatal growth for VLBW infants. STUDY DESIGN: Randomized clinical trial. Sixty-four infants were enrolled (34 in control group with 15 infants <1000 g, and 30 in intervention group with 13 infants <1000 g). RESULT: There were no sustained statistical differences between weekly measurements of weight, length, head circumference, and skinfold thickness between groups. There were no significant differences between laboratory results except blood urea nitrogen at time of peak protein intake for intervention group. CONCLUSIONS: Supplemental enteral protein had minimal to no effect on postnatal weight, length, head circumference, body mass, or length of stay. It may be most important to provide consistent sustained nutritional support with protein from birth to reduce postnatal growth restriction, especially for those infants <1000 g at birth.

A new degraded auditory stimulus test to measure implicit memory during anaesthesia in children.

It remains unclear whether children form implicit memories during general anaesthesia. This is partly due to a lack of tests for implicit memory that are appropriate for the anaesthesia setting. The aim of this study was to assess a new implicit memory test that could be more suitable for use with children during anaesthesia. Ninety-three children aged five to 12 years who were undergoing elective surgery were studied. Patients were randomly assigned to one of two groups preoperatively and exposed to a familiar animal sound, followed by a distractor task. Two animal sounds were tested; in one group children were exposed to one animal sound preoperatively, while in the other group they were exposed to the other. After surgery the children were played degraded versions of the animal sounds that had been mixed with white noise and became increasingly clearer over the 60 second recording. Children who explicitly recalled hearing the sound preoperatively were excluded. Response times for recognition were recorded and compared. The analysis revealed evidence for a significant priming effect for one of the two animal sounds tested. The speed and simplicity of administration of this test suggest the degraded auditory stimulus test would be a promising tool to detect implicit memory during anaesthesia in children. However as we found evidence for priming with only one of the sounds, the choice of sound is important.

Haemoglobin A2' and its significance in beta thalassaemia diagnosis.

We have studied, haemoglobin A(2)' (A(2) prime), a delta chain variant haemoglobin occurring in a small percentage of individuals of African ancestry. In heterozygotes, the percentage of haemoglobin A(2)' was found to be slightly lower then the percentage of haemoglobin A(2), suggesting that the variant delta chain is synthesized at a reduced rate. When quantifying haemoglobin A(2) for the diagnosis of beta thalassaemia heterozygosity, it is essential to add together the A(2) and A(2)' to give 'total haemoglobin A(2)'. However, it not necessary to use a different reference range for total haemoglobin A(2) in A(2)' heterozygotes. When using microcolumn chromatography, A(2)' was found to be measured with A(2). On the high-performance liquid chromatography instrument studied, haemoglobin A(2)' fell in the haemoglobin S window but its retention time differed from that of haemoglobin S.

Inaccuracy of high-performance liquid chromatography estimation of haemoglobin F in the presence of increased haemoglobin A1c.

Increasingly high-performance liquid chromatography is being used for identification and quantification of normal and variant haemoglobins. In many laboratories, the Beta Thal Short programme of the Bio-Rad Variant II instrument is used for this purpose. We noted that a factitious elevation of haemoglobin F was sometimes observed in diabetic patients and therefore carried out a systematic study of this phenomenon. We found discrepant results in 41% of samples from diabetic patients but in no normal volunteers. This factitious elevation could be predicted from a retention time for haemoglobin F of more than 1.15 min, the normal retention time being 1.08-1.15 min. Haemoglobinopathy laboratories need to be alert to the possibility of this erroneous result.

Reassessment of a simple chemical method using DCIP for screening for haemoglobin E.

BACKGROUND: Haemoglobin E is a variant haemoglobin that can lead to considerable morbidity in compound heterozygous states with beta thalassaemia. Therefore, its detection is important because it permits antenatal counselling. The parts of the world where haemoglobin E is prevalent are resource poor and detection can therefore be problematical. A simple visual test using 2,6-dichlorophenolindophenol (DCIP) has been developed in Thailand, but its use has not become widespread. This test has now become available in kit form. AIMS/METHODS: To evaluate the new DCIP test kit for the detection of haemoglobin E. RESULTS: Seventeen of 18 samples from individuals with haemoglobin E gave positive results and one gave an equivocal result. False positive or equivocal results were seen in three of 21 individuals with other disorders of globin chain synthesis but were not seen in normal subjects. CONCLUSIONS: This study evaluated the sensitivity, specificity, and reproducibility of the kit and confirmed the usefulness of the DCIP test as a screening test for haemoglobin E. In countries with limited health resources, its use would reduce the number of samples requiring referral to a central laboratory for definitive tests.

Some observations on the measurement of haemoglobin A2 and S percentages by high performance liquid chromatography in the presence and absence of alpha thalassaemia.

AIMS: To assess the accuracy and precision of measuring haemoglobin A(2) by high performance liquid chromatography (HPLC) in the presence and absence of sickle cell trait, with or without alpha thalassaemia trait. METHODS: The haemoglobin A(2) percentage and the haemoglobin A(2) plus S percentages were determined by HPLC on 82 normal controls and 78 patients with sickle cell trait, respectively; the alpha thalassaemia status of each patient was determined by polymerase chain reaction. Red cell indices and haemoglobin A(2) and S percentages were compared in patients with two, three, or four alpha genes. RESULTS: Of the 78 patients with sickle cell trait, 17 were heterozygous for alpha(+) thalassaemia (-alpha(3.7)/alphaalpha) and 13 were homozygous (-alpha(3.7)/-alpha(3.7)). Microcolumn chromatography showed that the haemoglobin A(2) percentage was slightly, but significantly, higher than normal in sickle cell trait. HPLC determinations of haemoglobin A(2) percentage in patients with sickle cell trait are precise but inaccurate, the percentage being appreciably overestimated. The measured haemoglobin A(2) percentage is stable for one week, but inaccuracy increases by two weeks in most samples. Despite this inaccuracy, there are significant differences in the HPLC "haemoglobin A(2) percentage" between groups of individuals with two, three, and four alpha genes. CONCLUSIONS: Haemoglobin A(2) determinations by HPLC are precise but inaccurate. Nevertheless, there are significant differences in the haemoglobin A(2) percentage in subjects with two, three, and four alpha genes. Although there is some overlap between groups, this can be useful, together with the red cell indices, in predicting the likelihood of coexisting alpha thalassaemia.

Introducing external cephalic version to clinical practice.

A service offering external cephalic version to all women with breech presentations at 36-38 weeks' gestation was introduced at St George Hospital in July 1997. This paper describes how this service was established and reports the clinical outcomes over the first three years; 116 external cephalic versions (ECV) were attempted on 114 women and success was achieved in 58 women (51%). Of the 58 women, 43 (74%) subsequently had vaginal deliveries. There were no fetal deaths, immediate Caesarean sections, or placental abruptions as a result of the ECV procedure. There were two (2%) episodes of transient fetal bradycardia following ECV, both of which returned to normal with a subsequent normal neonatal outcome. Pre- and post-ECV Kleihauer levels were collected with no increase in levels as a result of the ECV ECV is a procedure that can, and should, be provided as part of a public hospital service.

Evaluation of a new screening test for sickle cell haemoglobin.

A new kit for screening for sickle cell haemoglobin (haemoglobin S) has been evaluated. The kit is based on the principle that cells containing haemoglobin S, which have been induced to sickle by exposure to a reducing agent in a phosphate buffer, do not pass through a gel contained in microtubules. In theory, they can thus be distinguished from cells that do not contain haemoglobin S. In practice, the kit was found to be insensitive and unreliable for the detection of haemoglobin S. Homozygosity and heterozygosity for haemoglobin S could not be reliably distinguished. Similarly, patients with haemoglobin S who had been transfused could not be distinguished reliably from those who had not been transfused. In conclusion, unless improved performance can be demonstrated, use of this kit cannot be recommended.

Clinical research in paediatric oncology and the role of the research nurse in the UK.

Survival rates for childhood cancer have improved considerably as new drugs, treatment protocols and supportive therapies have developed through clinical trials. Such studies take a considerable amount of time and organization and alongside scientific and medical staff the research nurse plays a vital role. The facets of this role will be outlined in this paper. Involvement begins at an early stage of study development and includes applying for Research Ethics Committee approval of the project. Once the study has opened the research nurse is then responsible for patient recruitment, monitoring and follow-up. The research nurse works within a team but also with a degree of autonomy ensuring that standards of patient care are maintained by adhering to guidelines for clinical research in general and those aimed at children specifically. Providing detailed information and support to the child and family, staff and outside agencies are other notable aspects of the post. The role of the research nurse continues to develop, as clinical trials maintain a significant role in improving the treatment for childhood cancer.

An analysis of relative costs and potential benefits of different policies for antenatal screening for beta thalassaemia trait and variant haemoglobins.

AIMS: To investigate the costs and potential benefits of different policies for antenatal screening for haemoglobinopathies in two multiethnic London communities. METHODS: 1000 consecutive antenatal patient samples referred to each of two London teaching hospital laboratories for haemoglobinopathy testing were investigated using the standard procedures of the laboratory in question. When the standard procedures did not include high performance liquid chromatography (HPLC), this technique was added, in order to assess its diagnostic value and cost-effectiveness. A comparison was made between the costs and potential benefits of universal testing for variant haemoglobins and beta thalassaemia trait using HPLC and the costs and potential benefits of universal testing for variant haemoglobins and selective testing for beta thalassaemia trait using the mean cell haemoglobin (MCH) as a screening test and less automated techniques than HPLC for definitive diagnosis. RESULTS: The costs of the two policies were found to be comparable, as the higher reagent/instrument costs of HPLC were offset by the lower labour costs. Universal testing of 2000 consecutive samples did not disclose any extra cases of beta thalassaemia trait which would not have been detected by universal screening and selective testing. However, six patients were found to have a haemoglobin A2 variant which can interfere with the diagnosis of beta thalassaemia trait. CONCLUSIONS: The introduction of universal testing by HPLC into British laboratories could be cost neutral and has potential benefits. If a higher cost is accepted then the greater degree of automation could be used to release skilled staff for other tasks within the laboratory.

Endometrial thickness: individual and mean growth profiles for different hormone replacement regimens.

Currently, there is a paucity of data describing endometrial growth, with most studies concentrating on endometrial thickness immediately prior to implantation or embryo transfer. This study looked at the individual and combined growth profiles of 67 volunteers receiving three different hormone replacement regimens. Each treatment regimen was in excess of that considered necessary for optimal growth, and all promoted an endometrial thickness that would be considered satisfactory for embryo transfer. Three patterns of growth were identified, but overall there was a decrease in the rate of endometrial growth with duration of treatment. As expected, analysis of variance did not show a significant difference between the mean growth profiles for the three hormone replacement regimens. The correlation (r = 0.45, P < 0.0001) between rank order on day 3 and day 10 of treatment indicates that interim analysis during early treatment cannot accurately predict later thickness, but a doubling of endometrial thickness can be expected in most cases. A relationship between endometrial thickness and either the treatment dose or serum concentrations of oestradiol was not found. These findings suggest that manipulation of endometrial growth is not possible by adjustment of either the treatment dose or serum concentration. The findings indicate that treatment beyond 12 days does not promote either a clinically significant increase in endometrial thickness of an excessive thickness, suggesting that maintenance of an oocyte recipient in a pseudo-follicular phase is unlikely to be disadvantageous to implantation.

Screening criteria for beta thalassaemia trait in pregnant women.

AIMS: To establish suitable screening criteria for beta thalassaemia trait during pregnancy using an automated blood counter incorporating light scattering technology. METHODS: Pregnant women (n = 857) at a London antenatal clinic were investigated for beta thalassaemia trait if the Technicon H.2 full blood count showed either a mean corpuscular volume (MCV) < 85 fl or a mean corpuscular haemoglobin (MCH) < 27 pg. Results were then analysed to establish which of these variables was more suitable for screening and to determine suitable cut off points for calculating the haemoglobin A2 percentage. RESULTS: The MCH was superior to the MCV for thalassaemia screening as it was a more stable measurement and fewer unnecessary tests were performed. A MCH less than 27 pg is a suitable cut off point for screening. This screening criterion was equally applicable to a Coulter impedance counter. CONCLUSIONS: Pregnant women presenting at an antenatal clinic with a MCH < 27 pg should be investigated further to confirm or exclude a diagnosis of beta thalassaemia trait.

The value of screening tests for glucose-6-phosphate dehydrogenase deficiency.

The performances of two commercial screening tests for glucose-6-phosphate dehydrogenase deficiency (Sigma fluorescent spot test and Sigma colorimetric method) were assessed in order to determine their usefulness in a routine haematology laboratory. As a first step, three ranges for enzyme activity were determined as follows: a 'normal' range determined from the 95% confidence limit of assays carried out on 114 normal adult males, a deficient range calculated as 25% of the upper limit of normal or less, and an intermediate range between the lower and upper values of these ranges. These values were 4.9-11.8 u/g Hb, 0-2.9 u/g Hb and 3.0-4.8 u/g Hb respectively. A separate normal range was also determined for females and was 5.5-12.8 u/g Hb. The two screening tests were then assessed against these values and the kits were found to be equally reliable at predicting normals and deficients but less reliable at detecting all female heterozygotes. The criteria for using the different procedures were evaluated. It is concluded that screening procedures are useful only when a large number of tests are routinely performed or in the absence of facilities for assays, as they offer no advantage in cost or time over the assay procedure. The colorimetric test (single vials) is easier and cheaper to use if isolated tests are performed, whereas the fluorescent spot test (with some modifications) is more useful for carrying out numerous tests simultaneously.