Role of routine lymph node dissection alongside resection of intrahepatic cholangiocarcinoma: Systematic review and meta-analysis.

BACKGROUND: The global incidence of intrahepatic cholangiocarcinoma (ICCA) is soaring. Due to often delayed presentation, only a narrow spectrum of the disease is usually surgically resectable. To more accurately stage the disease, reduce recurrence, and improve overall survival, surgical teams are increasingly performing intraoperative lymph node dissection (LND) as well. This procedure has its associated morbidity, while there is no consensus or formal guidelines on its role in this setting. Hence, there is a need to better delineate the evidence for performing LND alongside surgical resection of the ICCA. AIM: To perform a systematic review and meta-analysis on the role of LND in improving prognostication and survival post-resection of ICCA. METHODS: We performed a systematic literature search using Pubmed, Medline, Embase, and the Cochrane Library, for all studies involving LND, ICCA, and surgical resection using several keywords, Medical Subject Headings (MeSH) tags, and appropriate synonyms. All clinical studies comparing curative intent resection of ICCA with LND vs resection without LND were included, while single-arm case series, studies with insufficient data, and duplicates were excluded. We included all English-language studies from the different academic databases up till early December 2022. The primary outcome measures were set for overall survival (OS) and disease-free survival (DFS). RESULTS: This systematic review and meta-analysis included 15 studies that fulfilled the selection criteria comprising 11413 patients with surgically-resectable ICCA, of whom 6424 (56.3%) underwent hepatectomy with LND while the remainder underwent hepatectomy only. In patients who underwent LND, on average, 27.7% of the resected lymph nodes were positive for metastatic disease. Overall, the results showed that performing LND did not significantly improve OS or DFS. However, the effect of LND on OS showed a degree of variability by geographical region, in Eastern and Western countries. As LND is increasingly being performed, further time-based analysis was undertaken to identify time-dependent changes in the role of LND. An increasing adoption of LND was not associated with improved OS. Furthermore, no roles were identified for neoadjuvant/adjuvant chemotherapy or increasing lymph node retrieval in improving OS either. CONCLUSION: LND might aid in staging, prognosticating, and deciding further management of resected ICCA, but does not improve OS and DFS and is unsuitable for high-risk patients unlikely to benefit from further treatments.

Management Strategies and Outcomes for Small Intestinal Neuroendocrine Tumours with Involvement of the Superior Mesenteric Vessels: A Systematic Review.

Small intestinal neuroendocrine tumours (SI-NETs) are the most common small intestinal tumours. A particularly challenging subset of these tumours is those that involve the superior mesenteric artery or vein for which the role and feasibility of surgery are often questioned. This systematic review aimed to identify and evaluate the management strategies used for these complex SI-NETs. The identified studies showed positive outcomes with surgery and multimodality therapy.

Liver transplantation in the management of cholangiocarcinoma: Evolution and contemporary advances.

Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the biliary epithelium. It may occur at any location along the biliary tree with the perihilar area being the most common. Prognosis is poor with 5-year overall survival at less than 10%, typically due to unresectable disease at presentation. Radical surgical resection with clear margins offers a chance of cure in patients with resectable tumours, but is frequently not possible due to locally advanced disease. On the other hand, orthotopic liver transplantation (LT) allows for a radical and potentially curative resection for these patients, but has been historically controversial due to the limited supply of donor grafts and previously poor outcomes. In patients with perihilar CCA, within specific criteria and following the implementation of a protocol combining neoadjuvant chemoradiation and LT, excellent results have been achieved in the last decades, resulting in its increasing acceptance as an indication for LT and the standard of care in several centres with significant experience. However, in intrahepatic CCA, the role of LT remains controversial and owing to dismal previous results it is not an accepted indication. Nevertheless, more recent studies have demonstrated favourable results with LT in early intrahepatic CCA, indicating that, under defined criteria, its role may increase in the future. This review highlights the history and contemporary advances of LT in CCA, with particular focus on the improving outcomes of LT in intrahepatic and perihilar CCA and future perspectives.

Stereotactic radiotherapy for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy with an increasing incidence worldwide and poor prognosis, despite several advances and continuous efforts to develop effective treatments. Complete surgical resection is the mainstay of treatment and offers a potentially curative option, but is only possible in less than a third of patients, owing to advanced disease. Chemotherapy is a well-established treatment in the adjuvant and palliative setting, however, confers limited benefit. Conventional radiotherapy is challenging due to local toxicity. With recent advances in stereotactic ablative radiotherapy (SABR), it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera. This review details the history, technical background and application of SABR to iCCA, with directions for future research suggested.

Assessing the Impact of Primary Tumour Location on Survival After Resection of Colorectal Liver Metastases: A Propensity Weighted Retrospective Cohort Study.

BACKGROUND: Right-sided colonic tumours appear to have poorer survival after resection of colorectal liver metastases, although this may be confounded by various factors including advanced stage and emergency presentation. METHODS: Medical records of consecutive patients undergoing resection of colorectal liver metastases at a single centre from 2008 to 2015 were retrospectively reviewed. Cases were categorised by primary tumour location (right colon, left colon, rectum). Each primary location was weighted using propensity scores to balance covariates, including staging and mode of presentation. Cox regression was then applied to derive multivariable hazard ratios (HR) of survival after liver resection. Primary outcomes were 10-year overall survival (OS) and 5-year disease-free survival (DFS) after liver resection based on PTL. RESULTS: 414 patients were included in the analysis. Left colonic tumours were significantly associated with higher rates of bilobar liver metastasis (36.2% vs. 20.1% and 30.1%) and larger maximum size of liver metastases compared with rectal and right-sided tumours, respectively. There was no difference in rates of extra-hepatic metastases, recurrence in the liver after resection or RAS, BRAF or p53 mutational status. After propensity weighting and Cox-regression, right-sided tumours were independently associated with significantly reduced 10 year OS (HR 1.56, 95% CI 1.03-2.36, p = 0.04) but not 5 year DFS (HR 1.36, 95% CI 0.89-2.08, p = 0.15). CONCLUSIONS: Compared with left colonic and rectal tumours, right-sided colonic tumours are independently associated with inferior OS after resection of CRLM. This is despite higher rates of bilobar liver metastases and larger metastases with left-sided tumours.

Evaluation of an international medical E-learning course with natural language processing and machine learning.

BACKGROUND: In the context of the ongoing pandemic, e-learning has become essential to maintain existing medical educational programmes. Evaluation of such courses has thus far been on a small scale at single institutions. Further, systematic appraisal of the large volume of qualitative feedback generated by massive online e-learning courses manually is time consuming. This study aimed to evaluate the impact of an e-learning course targeting medical students collaborating in an international cohort study, with semi-automated analysis of feedback using text mining and machine learning methods. METHOD: This study was based on a multi-centre cohort study exploring gastrointestinal recovery following elective colorectal surgery. Collaborators were invited to complete a series of e-learning modules on key aspects of the study and complete a feedback questionnaire on the modules. Quantitative data were analysed using simple descriptive statistics. Qualitative data were analysed using text mining with most frequent words, sentiment analysis with the AFINN-111 and syuzhet lexicons and topic modelling using the Latent Dirichlet Allocation (LDA). RESULTS: One thousand six hundred and eleventh collaborators from 24 countries completed the e-learning course; 1396 (86.7%) were medical students; 1067 (66.2%) entered feedback. 1031 (96.6%) rated the quality of the course a 4/5 or higher (mean 4.56; SD 0.58). The mean sentiment score using the AFINN was + 1.54/5 (5: most positive; SD 1.19) and + 0.287/1 (1: most positive; SD 0.390) using syuzhet. LDA generated topics consolidated into the themes: (1) ease of use, (2) conciseness and (3) interactivity. CONCLUSIONS: E-learning can have high user satisfaction for training investigators of clinical studies and medical students. Natural language processing may be beneficial in analysis of large scale educational courses.

Patterns of comorbidity and psychopharmacology in adults with intellectual disability and attention deficit hyperactivity disorder: an UK national cross-sectional audit.

Background: Attention-deficit hyperactivity disorder (ADHD) is higher in people with intellectual disability (ID) compared to the general population. Available limited evidence suggests this population has increased psychological problems, diagnostic overshadowing and psychotropic prescribing. This audit Identifies and analyzes real-world characteristics, diagnostic practices, treatment, and management of ADHD in adults with ID.Research Design and Methods: Pooled retrospective case note data for people with ID and ADHD, collected from 30 organizations across the UK, were analyzed. Patients were classified into mild and moderate-profound ID groups. Associated mental health and neurodevelopmental co-morbidity, Demographics, concomitant psychotropics, and mental and behavioral concerns were collected. Group differences were reported using logistic regression models.Results: Of 445 participants, 73% had co-occurring autism spectrum disorder (ASD) and 65% were prescribed ADHD medications. Those on ADHD medication were less likely to be prescribed antipsychotics (p < 0.001) and antidepressants (p < 0.001). Multiple significant differences were found in ADHD medication response between ID groups and those with/without co-morbid ASD but not associated with challenging behavior reduction.Conclusions: High levels of neurodevelopmental and psychiatric comorbidity were found. ID severity and the presence of ASD appear to influence the use of certain psychotropic medications. Appropriate use of ADHD medication appears to reduce psychotropic polypharmacy.

Diagnostic accuracy of X-ray versus CT in COVID-19: a propensity-matched database study.

OBJECTIVES: To identify the diagnostic accuracy of common imaging modalities, chest X-ray (CXR) and CT, for diagnosis of COVID-19 in the general emergency population in the UK and to find the association between imaging features and outcomes in these patients. DESIGN: Retrospective analysis of electronic patient records. SETTING: Tertiary academic health science centre and designated centre for high consequence infectious diseases in London, UK. PARTICIPANTS: 1198 patients who attended the emergency department with paired reverse transcriptase PCR (RT-PCR) swabs for SARS-CoV-2 and CXR between 16 March and 16 April 2020. MAIN OUTCOME MEASURES: Sensitivity and specificity of CXR and CT for diagnosis of COVID-19 using the British Society of Thoracic Imaging reporting templates. Reference standard was any RT-PCR positive naso-oropharyngeal swab within 30 days of attendance. ORs of CXR in association with vital signs, laboratory values and 30-day outcomes were calculated. RESULTS: Sensitivity and specificity of CXR for COVID-19 diagnosis were 0.56 (95% CI 0.51 to 0.60) and 0.60 (95% CI 0.54 to 0.65), respectively. For CT scans, these were 0.85 (95% CI 0.79 to 0.90) and 0.50 (95% CI 0.41 to 0.60), respectively. This gave a statistically significant mean increase in sensitivity with CT of 29% (95% CI 19% to 38%, p<0.0001) compared with CXR. Specificity was not significantly different between the two modalities.CXR findings were not statistically significantly or clinically meaningfully associated with vital signs, laboratory parameters or 30-day outcomes. CONCLUSIONS: CT has substantially improved diagnostic performance over CXR in COVID-19. CT should be strongly considered in the initial assessment for suspected COVID-19. This gives potential for increased sensitivity and considerably faster turnaround time, where capacity allows and balanced against excess radiation exposure risk.

Day case vs inpatient total shoulder arthroplasty: A retrospective cohort study and cost-effectiveness analysis.

BACKGROUND: Day case total shoulder arthroplasty (TSA) is a novel approach, not widely practiced in Europe. We conducted a retrospective cohort study of patients comparing elective day case and inpatient TSAs in our United Kingdom centre. AIM: To evaluate the efficacy and cost-effectiveness of day case TSA compared to standard inpatient total shoulder arthroplasty. METHODS: All patients undergoing TSA between January 2017 and July 2018 were included. Outcome measures were: Change in abduction and extension 3 mo postoperatively; 30-d postoperative adverse events and re-admissions in day case and inpatient groups. We also conducted an economic evaluation of outpatient arthroplasty. Multivariate linear and logistic regression were used to adjust for demographic and operative covariates. RESULTS: Fifty nine patients were included, 18 d cases and 41 inpatients. There were no adverse events or re-admissions at 30 d postoperatively in either group. There were no significant differences in adjusted flexion (mean difference 16.4, 95%CI: 17.6-50.5, P = 0.337) or abduction (mean difference: 13.2, 95%CI: 18.4-44.9, P = 0.405) postoperatively between groups. Median savings with outpatient arthroplasty were £529 (interquartile range: 247.33-789, P < 0.0001). CONCLUSION: Day case TSA is a safe, effective procedure, with significant cost benefit. Wider use may be warranted in the United Kingdom and beyond, with potential for significant cost savings and improved efficiency.

Foley catheter for induction of labour: a UK observational study.

We conducted a prospective observational study of all inductions using Foley's catheter at our center between 2016 and 2018. Outcome data collected included induction to delivery time, mode of delivery, complication rates, patient and staff satisfaction. Ninety-nine women were included in our study. Median induction to delivery time was 28.3 h (IQR 19.7-34 h), 20 (20.2%) women required Caesarean section. No relevant complications were recorded. Patients and staff were satisfied with the technique overall.These results show transcervical Foley's catheter is a safe and effective method of induction of labour in the UK setting. It was shown to be feasible in the outpatient and previous Caesarean section groups.Impact statementWhat is already known on the subject? Foley catheter as an induction agent has already been shown to be as clinically effective as slow release prostaglandins with lower costs.What do the results of this study add? No study has been published on its use for routine inductions in the UK. Our results show that Foley's catheter is a safe, effective method for inducing labour in the UK.What are the implications of these findings for clinical practice and/or further research? This suggests this technique should be implemented more widely in the UK.

A comparative study of quantitative assessment with fluorine-18-fluorodeoxyglucose positron-emission tomography and endoscopic ultrasound in oesophageal cancer.

OBJECTIVES: This study aims to assess the correlation between PET/CT and endoscopic ultrasound (EUS) parameters in patients with oesophageal cancer. PATIENTS AND METHODS: All patients who had complete PET/CT and EUS staging performed for oesophageal cancer at our centre between 2010 and 2016 were included. Images were retrieved and analysed for a range of parameters including tumour length, volume and position relative to the aortic arch. RESULTS: Seventy patients were included in the main analysis. A strong correlation was found between EUS and PET/CT in the tumour length, the volume and the position of the tumour relative to the aortic arch. Regression modelling showed a reasonable predictive value for PET/CT in calculating EUS parameters, with r higher than 0.585 in some cases. CONCLUSION: Given the strong correlation between EUS and PET parameters, fluorine-18 fluorodeoxyglucose (F-FDG) PET can provide accurate information on the length and the volume of tumour in patients who either cannot tolerate EUS or have impassable strictures.

Hybrid SPECT/CT Imaging in the Management of Differentiated Thyroid Carcinoma

Differentiated thyroid cancer (DTC) has a good prognosis overall; however, lifelong follow-up is required for many cases. Radioiodine planar imaging with iodine-123 (I-123) or radioiodine-131 (I-131) remains the standard in the follow-up after initial surgery and ablation of residual thyroid tissue using I-131 therapy. Radioiodine imaging is also used in risk-stratifying and for staging of thyroid cancer, and in long-term follow-up. Unfortunately, the lack of anatomical detail on planar gamma camera imaging and superimposition of areas presenting with increased radioiodine uptake can make accurate diagnosis and localization of radioiodine-avid metastatic disease challenging, leading to false positive results and potentially to over-treatment of patients. Hybrid SPECT/CT allows precise anatomical localization and superior characterization of foci of increased tracer uptake when compared to planar imaging. This, in turn, allows the differentiation of pathological and physiological uptake, increasing the accuracy of image interpretation and ultimately improving the accuracy of DTC staging and subsequent patient management. In this review, we look at the unique and emerging role that SPECT/CT plays in the management of DTC, illustrated by examples from our own clinical practice.

The Risk of Deterioration in GCS13-15 Patients with Traumatic Brain Injury Identified by Computed Tomography Imaging: A Systematic Review and Meta-Analysis.

The optimal management of mild traumatic brain injury (TBI) patients with injuries identified by computed tomography (CT) brain scan is unclear. Some guidelines recommend hospital admission for an observation period of at least 24 h. Others argue that selected lower-risk patients can be discharged from the Emergency Department (ED). The objective of our review and meta-analysis was to estimate the risk of death, neurosurgical intervention, and clinical deterioration in mild TBI patients with injuries identified by CT brain scan, and assess which patient factors affect the risk of these outcomes. A systematic review and meta-analysis adhering to PRISMA standards of protocol and reporting were conducted. Study selection was performed by two independent reviewers. Meta-analysis using a random effects model was undertaken to estimate pooled risks for: clinical deterioration, neurosurgical intervention, and death. Meta-regression was used to explore between-study variation in outcome estimates using study population characteristics. Forty-nine primary studies and five reviews were identified that met the inclusion criteria. The estimated pooled risk for the outcomes of interest were: clinical deterioration 11.7% (95% confidence interval [CI]: 11.7%-15.8%), neurosurgical intervention 3.5% (95% CI: 2.2%-4.9%), and death 1.4% (95% CI: 0.8%-2.2%). Twenty-one studies presented within-study estimates of the effect of patient factors. Meta-regression of study characteristics and pooling of within-study estimates of risk factor effect found the following factors significantly affected the risk for adverse outcomes: age, initial Glasgow Coma Scale (GCS), type of injury, and anti-coagulation. The generalizability of many studies was limited due to population selection. Mild TBI patients with injuries identified by CT brain scan have a small but clinically important risk for serious adverse outcomes. This review has identified several prognostic factors; research is needed to derive and validate a usable clinical decision rule so that low-risk patients can be safely discharged from the ED.

A Systematic Review And Meta-Analysis of Clinical Trials of Mesenchymal Stem Cell Therapy for Cartilage Repair.

BACKGROUND: Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments. OBJECTIVE: We systematically reviewed clinical trials of MSCs for cartilage repair and provide an overview of the literature in this area here. MEDLINE, Embase, CENTRAL, clinicaltrials.gov and Open- Grey were searched for controlled trials and case series with >5 patents involving MSC therapy for cartilage repair. The controlled trials were meta-analysed and the primary outcome measure was improvement in pain over the control group. A narrative synthesis was composed for the case series. RESULTS: A significant reduction in pain was found with the use of MSCs over controls: Standardised mean difference=-1.27 (95% Confidence intervals -1.95 to -0.58). However, the data was extremely heterogeneous with I2=95%, this may be attributed to differing therapies, clinical indication for treatment and joints treated amongst others. Case series showed improvements in treated patients with a variety of differing treatments and by many outcomes. There were no severe adverse outcomes found across all studies that could be attributed to MSCs, implying their safety. CONCLUSION: We conclude that MSCs have significant potential for the treatment of OA, however, larger, more consistent trials are needed for conclusive analysis.

A prospective cohort study evaluating the cost-effectiveness of carbetocin for prevention of postpartum haemorrhage in caesarean sections.

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylaxis with oxytocic medication is recommended by the WHO to prevent its occurrence. Carbetocin is a newer oxytocic, with potential to lower PPH rates, reduce the total use of oxytocic drugs and lead to financial savings. Meta-analyses have confirmed a reduction in the use of additional oxytocic medication with the use of carbetocin compared to oxytocin. However, there are few studies evaluating the costs of carbetocin prophylaxis. We carried out a prospective cohort study evaluating the financial impact of carbetocin, following its introduction at our centre for caesarean section. We collected data for 400 patients in total, making this, to our knowledge, the largest study conducted on this topic. We found a significant reduction in PPH rates and the use of additional oxytocics with projected overall financial savings of £68.93 per patient with the use of carbetocin. Impact statement It is well established that carbetocin reduces the use of secondary oxytocics compared to oxytocin alone in the active management of the third stage of labour. Evidence for reduction of post-partum haemorrhage and its cost effectiveness are more equivocal. Our study demonstrates that carbetocin also reduces post-partum haemorrhage, use of blood and blood products and midwifery recovery time in the setting of caesarean section. We have also demonstrated that despite the increased index cost of carbetocin it delivers an overall substantial cost benefit. The implications of these findings are of reduced morbidity, faster recovery and cost savings in these times of austerity in the UK. It allows more efficient labour distribution of midwives, particularly in the setting of staff shortages across the NHS. A randomised control trial in this area needs to be conducted to determine the cost benefit of carbetocin and with this and post-partum haemorrhage rates as the primary outcome measures.