Oncological outcomes after pancreatoduodenectomy for pancreatic ductal adenocarcinoma in octogenarians: case-control study.

BACKGROUND: By the end of this decade, 70 per cent of all diagnosed pancreatic ductal adenocarcinomas will be in the elderly. Surgical resection is the only curative option. In the elderly perioperative mortality is higher, while controversy still exists as to whether aggressive treatment offers any survival benefit. This study aimed to assess the oncological benefit of pancreatoduodenectomy in octogenarians with pancreatic ductal adenocarcinoma. METHOD: Retrospective multicentre case-control study of octogenarians and younger controls who underwent pancreatoduodenectomy for pancreatic ductal adenocarcinoma between 2008 and 2017. The primary endpoint was overall survival and the secondary endpoint was disease-free survival. RESULTS: Overall, 220 patients were included. Although the Charlson co-morbidity index was higher in octogenerians, Eastern Cooperative Oncology Group performance status, ASA and pathological parameters were comparable. Adjuvant therapy was more frequently delivered in the younger group (n = 80, 73 per cent versus n = 58, 53 per cent, P = 0.006). There was no significant difference between octogenarians and controls in overall survival (20 versus 29 months, P = 0.095) or disease-free survival (19 versus 22 months, P = 0.742). On multivariable analysis, age was not an independent predictor of either oncological outcome measured. CONCLUSION: Octogenarians with pancreatic ductal adenocarcinoma of the head and uncinate process may benefit from comparable oncological outcomes to younger patients with surgical treatment. Due to the age- and disease-related frailty and co-morbidities, careful preoperative assessment and patient selection is of paramount importance.

Postcholecystectomy diarrhoea rate and predictive factors: a systematic review of the literature.

OBJECTIVES: Cholecystectomy is one of the most common surgical procedures performed worldwide to treat gallstone-related disease. Postcholecystectomy diarrhoea (PCD) is a well-reported phenomenon, however, the actual rate, predictive factors and mechanism of action have not been well determined. A systematic review was undertaken to determine the rate and predictive factors associated with diarrhoea in the postcholecystectomy setting. METHODS: The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. Databases searched included Medline, Embase, Pubmed, Cochrane and Google Scholar up to 29 September 2020. The inclusion criteria consisted of cohort studies or randomised trials which investigated the rate of PCD and predictive factors. Case reports, case series, conference abstracts and expert opinion pieces were excluded as were other systematic reviews as all the original articles from those reviews were included in this review. Papers that did not include PCD as a separate entity were excluded. Bias assessment was performed using the Newcastle-Ottawa Scale for cohort studies and the Cochrane risk of bias tool for randomised controlled trials as appropriate. Data were extracted by two authors (AF and JAA) and an overall rate of PCD was calculated. Predictive factors were also extracted and compared between studies. RESULTS: 1204 papers were obtained and 21 were found to contain relevant information about PCD, including the number of patients developing diarrhoea, method of symptom assessment and time of onset postcholecystectomy. A pooled total of 3476 patients were included across the identified studies with 462 (13.3%) patients developing PCD. Possible predictive factors varied across all studies, with characteristics such as gender, age and weight of patients postulated as being predictive of PCD, with no agreement across studies. DISCUSSION: PCD is therefore relatively common (13.3%). This has important implications for patient consent. Patients ought to be investigated early for bile acid diarrhoea in suspected PCD. More studies are required to determine the possible predictive factors for PCD. Limitations of the study included that most studies were not powered for calculation of PCD, and assessment methods between studies varied. PROSPERO REGISTRATION NUMBER: CRD42019140444.

Proposed training pathway with initial experience to set up robotic hepatobiliary and pancreatic service.

Although robot-assisted hepatobiliary and pancreatic (HPB) surgery has gained momentum over the last 2 decades, only a handful of units in the world perform major robotic resections. Adaptation of robotic surgery in the UK lags behind its European counterparts and this is mainly because of cost implications in a publicly funded National Health Service (NHS). We describe our experience of setting up a robotic HPB programme with clinical outcomes and propose a training pathway that would help prospective centres in setting up their own robotic HPB service with robust clinical governance oversight. After gaining colleagues' and departmental support, approval from the hospital clinical governance, finance department and new intervention procedure committee was sought. A team of two consultant surgeons, three assistants and three theatre staff went through a structured training programme sponsored mainly by the industry. Surgeon training consisted of online modules, simulation, wet lab, cadaveric training, case observations, proctored procedures followed by independent practice. All major cases were recorded and videos reviewed to improve performance. A total of 111 procedures were successfully completed with robotic assistance between April 2018 and March 2020. The programme started with robot-assisted cholecystectomy as index procedure and progressed on to more complex liver and pancreatic resections including major hepatectomy and Whipple's procedure. The training pathway followed by our team has been effective in setting up a safe robotic HPB programme and could be considered as a roadmap to start new Robotic HPB services.

Short-term outcomes after pancreatoduodenectomy in octogenarians: multicentre case-control study.

BACKGROUND: Pancreatoduodenectomy (PD) is frequently the surgical treatment indicated for a number of pathologies. Elderly patients may be denied surgery because of concerns over poor perioperative outcomes. The aim of this study was to evaluate postoperative clinical outcomes and provide evidence on current UK practice in the elderly population after PD. METHODS: This was a multicentre retrospective case-control study of octogenarians undergoing PD between January 2008 and December 2017, matched with younger controls from seven specialist centres in the UK. The primary endpoint was 90-day mortality. Secondary endpoints were index admission mortality, postoperative complications, and 30-day readmission rates. RESULTS: In total, 235 octogenarians (median age 81 (range 80-90) years) and 235 controls (age 67 (31-79) years) were included in the study. Eastern Cooperative Oncology Group performance status (median 0 (range 0-3) versus 0 (0-2); P = 0.010) and Charlson Co-morbidity Index score (7 (6-11) versus 5 (2-9); P = 0.001) were higher for octogenarians than controls. Postoperative complication and 30-day readmission rates were comparable. The 90-day mortality rate was higher among octogenarians (9 versus 3 per cent; P = 0.030). Index admission mortality rates were comparable (4 versus 2 per cent; P = 0.160), indicating that the difference in mortality was related to deaths after hospital discharge. Despite the higher 90-day mortality rate in the octogenarian population, multivariable Cox regression analysis did not identify age as an independent predictor of postoperative mortality. CONCLUSION: Despite careful patient selection and comparable index admission mortality, 90-day and, particularly, out-of-hospital mortality rates were higher in octogenarians.

Bile acid diarrhoea: pathophysiology, diagnosis and management.

The actual incidence of bile acid diarrhoea (BAD) is unknown, however, there is increasing evidence that it is misdiagnosed in up to 30% with diarrhoea-predominant patients with irritable bowel syndrome. Besides this, it may also occur following cholecystectomy, infectious diarrhoea and pelvic chemoradiotherapy. BAD may result from either hepatic overproduction of bile acids or their malabsorption in the terminal ileum. It can result in symptoms such as bowel frequency, urgency, nocturnal defecation, excessive flatulence, abdominal pain and incontinence of stool. Bile acid synthesis is regulated by negative feedback loops related to the enterohepatic circulation, which are dependent on the farnesoid X receptor and fibroblast growth factor 19. Interruption of these feedback loops is thought to cause bile acid overproduction leading to BAD. This process may occur idiopathically or following a specific trigger such as cholecystectomy. There may also be an interplay with the gut microbiota, which has been reported to be significantly different in patients with severe BAD. Patients with suspected BAD are investigated in various ways including radionucleotide imaging such as SeHCAT scans (though this is not available worldwide) and blood tests. However, other methods such as bile acid measurement in stool (either spot test or 48 hours samples) and urine tests have been explored. Importantly, delay in diagnosis and treatment of BAD greatly affects patient's quality of life and may double the overall cost of diagnosis.

Performance of the faecal immunochemical test for the detection of colorectal neoplasms and the role of proton pump inhibitors in their diagnostic accuracy.

AIM: The faecal immunochemical test (FIT) is currently utilized in both symptomatic and screening populations, but little is known about factors that affect its performance. For example, proton pump inhibitor (PPI) therapy has been purported to increase false negative rates. This has significant implications given the extent of PPI prescriptions. The aim of this work was to evaluate the performance of the FIT for the detection of colorectal neoplasms and the impact of PPI therapy on its diagnostic accuracy. METHOD: Symptomatic patients referred on the suspected cancer pathway and those on polyp surveillance between 2015 and 2019 were approached to participate. Estimates of the accuracy of FIT at different cut-off levels in diagnosing colorectal neoplasms were made. Logistic regression was used to assess the effect of PPIs on the FIT results. RESULTS: A total of 667 participants were eligible for the final analysis. At a cut-off of 10 µg/g faeces, the overall sensitivity and specificity of FIT for the detection of colorectal cancer (CRC) was 0.85 (95% CI 0.71-0.94) and 0.81 (95% CI 0.78-0.84), respectively. For the detection of advanced neoplasia, the sensitivity was 0.70 (95% CI 0.58-0.79) and the specificity was 0.83 (95% CI 0.80-0.86). At higher thresholds, the sensitivity steadily declined whilst specificity increased. PPI therapy did not have a significant effect on performance of the FIT. CONCLUSION: FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.

Rates of Bile Acid Diarrhoea After Cholecystectomy: A Multicentre Audit.

INTRODUCTION: Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation, e.g. following cholecystectomy. Post-cholecystectomy diarrhoea has been reported in 2.1-57.2% of patients; however, this is not necessarily due to BAD. The aim of this study was to determine the rates of bile acid diarrhoea diagnosis after cholecystectomy and to consider investigation practices. METHODS: A retrospective analysis of electronic databases from five large centres detailing patients who underwent laparoscopic cholecystectomy between 2013 and 2017 was cross-referenced with a list of patients who underwent 75SeHCAT testing. A 7-day retention time of <15% was deemed to be positive. Patient demographics and time from surgery to investigation were collected and compared for significance (p < 0.05). RESULTS: A total of 9439 patients underwent a laparoscopic cholecystectomy between 1 January 2013 and 31 December 2017 in the five centres. In total, 202 patients (2.1%) underwent investigation for diarrhoea via 75SeHCAT, of which 64 patients (31.6%) had a 75SeHCAT test result of >15%, while 62.8% of those investigated were diagnosed with bile acid diarrhoea (BAD). In total, 133 (65.8%) patients also underwent endoscopy and 74 (36.6%) patients had a CT scan. Median time from surgery to 75SeHCAT test was 672 days (SD ± 482 days). DISCUSSION/CONCLUSION: Only a small proportion of patients, post-cholecystectomy, were investigated for diarrhoea with significant time delay to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher, and clinicians need to have an increased awareness of this condition due to its amenability to treatment. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea.

Treatment Strategies for the Optimal Management of Locally Advanced Pancreatic Adenocarcinoma With Curative Intent: A Systematic Review.

Historically, locally advanced pancreatic adenocarcinoma (LAPDAC) was considered a palliative condition. Advances in treatment have resulted in studies reporting survival after neoadjuvant treatment and surgery similar to earlier disease stages. However, there is no consensus on optimal LAPDAC management. Our aim was a systematic review of published evidence on LAPDAC treatment strategies with curative intent. Twenty-eight studies defining LAPDAC as per established criteria and reporting outcomes after neoadjuvant treatment with a view to resection were included. Primary outcomes were resection rate and proportion of curative resections. Secondary outcomes were postoperative mortality, progression-free survival, and overall survival. Neoadjuvant treatment varied significantly, most common being the combination of folinic acid, fluorouracil, irontecan, and oxaliplatin. Median percentage of patients proceeding to surgery after completion of neoadjuvant pathway was 33.5%. Median resection rate was 25%. Median R0 resection was 80% of resected patients. These outcomes ranged 0% to 100% across studies. Ninety-day postoperative mortality ranged from 0% to 5%. Median progression-free and overall survival for resected patients were 12.9 and 30 months, respectively, versus 13.2 months overall survival for unresected patients. In conclusion, although there is wide variability in reported LAPDAC resection rates post-neoadjuvant chemotherapy, retrospective data suggest that neoadjuvant treatment followed by surgery results in improved survival.

COVID-19: mobilising CT as a frontline management tool.

As the COVID-19 pandemic has spread across the globe, questions have arisen about the approach healthcare systems should adopt in order to optimally manage patient influx. With a focus on the impact of COVID-19 on the NHS, we describe the frontline experience of a severely affected hospital in close proximity to London. We highlight a protocol-driven approach, incorporating the use of CT in the rapid triage, assessment and cohorting of patients, in an environment where there was a lack of readily available, onsite RT-PCR testing facilities. Furthermore, the effects of the protocol on the effective streamlining of patient flow within the hospital are discussed, as are the resultant improvements in clinical management decisions within the acute care service. This model may help other healthcare systems in managing this pandemic whilst assessing their own needs and resources.

C-reactive protein and albumin association with mortality of hospitalised SARS-CoV-2 patients: A tertiary hospital experience.

OBJECTIVE: The objective was to study hospitalised COVID-19 patients' mortality and intensive care unit (ICU) admission with covariates of interest (age, gender, ethnicity, clinical presentation, comorbidities and admission laboratory findings). METHODS: Logistic regression analyses were performed for patients admitted to University Hospital, University Hospitals Coventry and Warwickshire NHS Trust, between 24 January 2020 - 13 April 2020. RESULTS: There were 321 patients hospitalised. Median age was 73 years and 189 (59%) were male. Ethnicity was divided between Caucasian (77%), and black, Asian, and minority ethnic (BAME) groups (23%). Commonest symptoms were dyspnoea (62.9%), fever (59.1%) and cough (56%). Gastrointestinal symptoms amounted to 11.8%.Forty-four patients (13.7%) received ICU care. ICU male to female ratio was 3:1 (p=0.027; odds ratio (OR) 2.3; 95% confidence interval (CI) 1.1-4.9), BAME (p=0.008; OR 2.5; 95% CI 1.3-4.9), age >65 years (p=0.026; OR 0.28; 95% CI 0.09-0.93), heart disease (p=0.009; OR 0.2; 95% CI 0.1-0.6) and elevated C-reactive protein (CRP; p<0.001; OR 1.004; 95% CI 1.002-1.008) were associated with ICU admission.One-hundred and four patients (32.4%) died. Age >65 years (p=0.011; OR 5; 95% CI 1.6-21.9), neutrophils (p=0.047), neutrophil:lymphocyte ratio (NLR; p=0.028), CRP (p<0.001) and albumin (p=0.002) were associated with mortality. When analysis adjusted for age, CRP (p<0.001; OR 1.006; 95% CI 1.004-1.008) and albumin (p=0.005; OR 0.94; 95% CI 0.90-0.98) remained associated with mortality. CONCLUSIONS: COVID-19 has high mortality. BAME and male patients were associated with ICU admission. High CRP and low albumin (after correcting for age) were associated with mortality.

Multivisceral robotic resection: a glimpse into the future of minimally invasive abdominal surgery.

A 62-year-old man was referred to the Hepato-Pancreato-Biliary (HPB) surgeons with left upper quadrant discomfort. The initial investigations and CT scans revealed a tumour in the pancreatic tail with liver metastases, confirmed on MRI. It was initially thought to be an adenocarcinoma; however, further investigations found that it was a grade 1 neuroendocrine tumour with Ki 67 at 1% and it was agreed that he would undergo a total robotic surgery involving resection of the locally advanced tumour of the tail of pancreas, with the involvement of the stomach, and splenic flexure of the colon with liver metastases. The resulting procedure was a total robotic distal pancreatectomy, splenectomy, sleeve resection of stomach, cholecystectomy, atypical resection of two liver lesions and microwave ablation of multiple liver lesions. Four days post-operatively, he was discharged from hospital and commenced adjuvant chemotherapy. He currently enjoys a good quality of life.

Faecal immunochemical testing (FIT) in symptomatic patients: what are we missing?

OBJECTIVE: Faecal immunochemical test (FIT) shows promise as a non-invasive triage test for colorectal cancer (CRC) in the symptomatic population. The aim of this study was to assess the use of FIT within the recent NG12 and DG30 National Institute for Health and Care Excellence (NICE) guidelines. DESIGN: A single-centre prospective study of patients referred to University Hospitals Coventry and Warwickshire NHS Trust via the 2-week wait (TWW) pathway between January 2015 and March 2016 was conducted. 612 patients were reviewed, of which 519 were found to meet the NG12 criteria and 79 met the DG30 criteria. Data included age, sex, symptoms, colonoscopy or CT colonography, histology and FIT results. MAIN OUTCOME MEASURES: FIT was performed in all patients and sensitivity, specificity, positive predictive value and negative predictive value, with 95% CI, for cancers and adenomas within each pathway (TWW, NG12 and DG30) was calculated. RESULTS: CRC sensitivity in TWW pathway patients, NG12 and DG30 group was 86.84% (95% CI 71.91% to 95.59%), 84.85% (95% CI 68.1% to 94.89%) and 100% (95% CI 47.82% to 100%), respectively. Specificity was 82.23% (95% CI 78.85% to 85.27%), 81.28% (95% CI 77.52% to 84.65%) and 91.89% (95% CI 83.18% to 96.97%), respectively. Adenoma sensitivity in the groups was 30.69% (95% CI 29.9% to 40.66%), 30.77% (95% CI 21.51% to 41.32%) and 25% (95% CI 3.19% to 65.09%), respectively. CONCLUSION: Use of FIT within the remit of the NG12 NICE guidelines shows a high sensitivity and specificity and may be an effective triage tool when considering whether to perform investigations. However, there is still a miss rate. FIT within DG30 has excellent sensitivity and improved specificity; however, DG30 targets lower risk groups and accounts for only 13% of the entire referrals for suspected cancer. Therefore, managing the larger, higher risk NG12 group may require the addition of another test or marker to ensure that CRC is not missed.

Diagnosing Inflammatory bowel disease using noninvasive applications of volatile organic compounds: a systematic review.

Introduction: Inflammatory bowel disease (IBD) is a common disease with significant morbidity. Noninvasive diagnostic techniques are lacking in IBD. Currently, fecal calprotectin is a sensitive marker of gut inflammation however is not specific to Crohn's disease (CD) or ulcerative colitis (UC) alone. Volatile organic compounds (VOCs) were shown to have potential in IBD diagnosis.Areas covered: This systematic review aimed to examine the next-generation diagnosis of IBD in adults and children using VOCs. An in-depth literature-based search of current clinical studies of VOCs in the diagnosis of IBD was undertaken. Accuracy of IBD detection varied according to the technologies applied. Breath VOCs studies were pooled giving an overall sensitivity of 85% (95%CI: 79-89%) and specificity of 79% (95%CI 73-84%) whilst pooled fecal VOCs studies revealed a sensitivity of 87% (95%CI 77-93%) and specificity of 91% (95%CI 82-96%). Studies were limited by the variance of techniques applied in VOCs detection and the absence of well-designed longitudinal studies.Expert opinion: VOCs can be consistently and effectively detected in urine, breath, and stool in IBD patients. The sensitivity of breath VOCs in detecting IBD was comparable to feces. However, optimal VOCs detection methodology and biological sampling still need to be standardized..

Ciliated foregut cyst of the gall bladder: the largest ever described.

A 78-year-old man presented to the accident and emergency department with acute abdominal pain. A CT scan done to investigate the pain showed an intra-abdominal abscess medial to the caecum and an incidental exophytic lesion in the gall bladder. This was excised during surgery and sent for histological examination. Histology showed a ciliated foregut cyst of the gall bladder. A literature review revealed that this was the 13th case worldwide, as ciliated foregut cysts are usually found either above the diaphragm or in the liver. It was also the largest cyst described, with 45 mm diameter. So far none of these cysts found in the gall bladder have shown malignant transformation, though those found in the liver have been known to become malignant. Due to histological similarity, excision of ciliated foregut cysts of the gall bladder should be considered as there is still a risk of malignant transformation.