Costs and clinical benefits of enhanced recovery after surgery (ERAS) in pancreaticoduodenectomy: an updated systematic review and meta-analysis.

PURPOSE: ERAS is a holistic and multidisciplinary pathway that incorporates various evidence-based interventions to accelerate recovery and improve clinical outcomes. However, evidence on cost benefit of ERAS in pancreaticoduodenectomy remains scarce. This review aimed to investigate cost benefit, compliance, and clinical benefits of ERAS in pancreaticoduodenectomy. METHODS: A comprehensive literature search was conducted on Medline, Embase, PubMed, CINAHL and the Cochrane library to identify studies conducted between 2000 and 2021, comparing effect of ERAS programmes and traditional care on hospital cost, length of stay (LOS), complications, delayed gastric emptying (DGE), readmission, reoperation, mortality, and compliance. RESULTS: The search yielded 3 RCTs and 28 cohort studies. Hospital costs were significantly reduced in the ERAS group (SMD = - 1.41; CL, - 2.05 to - 0.77; P < 0.00001). LOS was shortened by 3.15 days (MD = - 3.15; CI, - 3.94 to - 2.36; P < 0.00001) in the ERAS group. Fewer patients in the ERAS group had complications (RR = 0.83; CI, 0.76-0.91; P < 0.0001). Incidences of DGE significantly decreased in the ERAS group (RR = 0.72; CI, 0.55-0.94; P = 0.01). The number of deaths was fewer in the ERAS group (RR = 0.76; CI, 0.58-1.00; P = 0.05). CONCLUSION: This review demonstrated that ERAS is safe and feasible in pancreaticoduodenectomy, improves clinical outcome such as LOS, complications, DGE and mortality rates, without changing readmissions and reoperations, while delivering significant cost savings. Higher compliance is associated with better clinical outcomes, especially LOS and complications.

Extrapulmonary tuberculosis presentation in the form of a chest wall abscess with no pulmonary involvement in the UK: a case report.

The presentation of an extrapulmonary manifestation of tuberculous (TB) infection to a tertiary care facility in the UK is a rare event given its low prevalence. This case report focuses on an atypical presentation of an extrapulmonary tuberculosis (EPTB) infection in the form of a chest wall abscess. This was recognized and managed appropriately. This case however elucidates vital learning as migration from around the globe would contribute to an increasing number of TB/EPTB infections. The wide array and indolent nature of their presentation creates diagnostic and treatment challenges. Appreciation for the epidemiology, risk factors, effective and prompt treatment with follow up protocols would help develop pathways for better care. Within the UK, despite it being a low-risk country for TB, there is need for increased awareness, education with established management pathways and governance for TB and EPTB infections.

Quality of Life and Medico-Legal Implications Following Iatrogenic Bile Duct Injuries.

In this review we aimed to evaluate quality of life after bile duct injury and the consequent medico-legal implications. A comprehensive English language literature search was performed on MEDLINE, Embase, Science Citation Index and Google™ Scholar databases for articles published between January 2000 and April 2016. The last date of search was 11 April 2016. Key search words included bile duct injury, iatrogenic, cholecystectomy, prevention, risks, outcomes, quality of life, litigation and were used in combination with the Boolean operators AND, OR and NOT. Long-term survival after bile duct injury is significantly impaired (all-cause long-term mortality approximately 21 %) along with the quality of life (especially psychological/mental state remains affected). Bile duct injury is associated with high rates of litigation. Monetary compensation varied from £2500 to £216,000 in the UK, €9826-€55,301 in the Netherlands and $628,138-$2,891,421 in the USA. Bile duct injuries have profound implications for patients, medical personnel and healthcare providers as they cause significant morbidity and mortality, high rates of litigation and raised healthcare expenditure.

The role of laparoscopy and laparoscopic ultrasound in the preoperative staging of patients with resectable colorectal liver metastases: a meta-analysis.

BACKGROUND: The role of staging laparoscopy (SL) with laparoscopic ultrasound (LUS) in patients with resectable colorectal liver metastases (CRLM) remains controversial. METHODS: A meta-analysis of all studies (from 1998 to the present) on the effect of SL/LUS in patients with potentially resectable CRLM with respect to alteration in surgical management was performed. RESULTS: Twelve studies satisfied the inclusion criteria. A total of 1,047 patients underwent SL/LUS. The true yield of SL/LUS for CRLM was 19% (95% confidence interval [CI], 16%-22%), with a diagnostic odds ratio of 132 (95% CI, 56-310) and an overall sensitivity of 59% (95% CI, 53%-65%). Subgroup analysis for detection of other liver and peritoneal lesions showed a sensitivity of 59% (95% CI, 49%-67%) and 75% (95% CI, 63%-85%) respectively. There was major between-study heterogeneity for all analyses, with no obvious cause revealed by meta-regression. CONCLUSIONS: The true benefit of using SL/LUS universally seems limited. It appears more useful as an adjunct in patients when peritoneal disease is suspected.

AGR2 is a novel surface antigen that promotes the dissemination of pancreatic cancer cells through regulation of cathepsins B and D.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers largely due to disseminated disease at the time of presentation. Here, we investigated the role and mechanism of action of the metastasis-associated protein anterior gradient 2 (AGR2) in the pathogenesis of pancreatic cancer. AGR2 was induced in all sporadic and familial pancreatic intraepithelial precursor lesions (PanIN), PDACs, circulating tumor cells, and metastases studied. Confocal microscopy and flow cytometric analyses indicated that AGR2 localized to the endoplasmic reticulum (ER) and the external surface of tumor cells. Furthermore, induction of AGR2 in tumor cells regulated the expression of several ER chaperones (PDI, CALU, RCN1), proteins of the ubiquitin-proteasome degradation pathway (HIP2, PSMB2, PSMA3, PSMC3, and PSMB4), and lysosomal proteases [cathepsin B (CTSB) and cathepsin D (CTSD)], in addition to promoting the secretion of the precursor form pro-CTSD. Importantly, the invasiveness of pancreatic cancer cells was proportional to the level of AGR2 expression. Functional downstream targets of the proinvasive activity of AGR2 included CTSB and CTSD in vitro, and AGR2, CTSB, and CTSD were essential for the dissemination of pancreatic cancer cells in vivo. Taken together, the results suggest that AGR2 promotes dissemination of pancreatic cancer and that its cell surface targeting may permit new strategies for early detection as well as therapeutic management.

Application of proteomics in cancer gene profiling: two-dimensional difference in gel electrophoresis (2D-DIGE).

In the post-genomic era, proteomic strategies are at the forefront of cancer research. By studying the complement of all expressed genes, proteomics aims to provide knowledge of biomarkers indicative of the physiological state of cancer cells at a specific time, enabling screening, early diagnosis, monitoring the course of cancer development/progression, and gauging the efficacy and safety of novel therapeutic agents. Onco-proteomics thus has the ability to revolutionize oncology practice by delivering highly selective and individualised clinical care. One of the proteomic techniques, two-dimensional (2D) difference in gel electrophoresis (DIGE) enables simultaneous examination and comparison of multiple samples using cyanine dyes to label amino acid residues that are then separated based on charge and mass. This technique reduces variability, improves reproducibility, and allows easier quantitation when compared with traditional 2D polyacrylamide gel electrophoresis (PAGE). These advantages combined with universal availability makes 2D-DIGE a first method of choice in cancer proteome analysis of diverse specimens, including tissues, cell lines, blood, and other body fluids.

Analysis of the urine proteome in patients with pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) accounts for over 213 000 deaths worldwide each year, largely due to late diagnosis. One of the risk factors for the development of PDAC is chronic pancreatitis (CP); the intense desmoplastic reaction makes differentiation between the two conditions extremely difficult. In order to identify biomarkers for noninvasive diagnosis, we performed 2-D DIGE analysis of urine samples from healthy individuals and patients with PDAC and CP. Despite considerable intersample heterogeneity, a total of 127 statistically valid (p<0.05), differentially expressed protein spots were detected, 101 of which were identified using MALDI-TOF MS. A number of these, including annexin A2, gelsolin and CD59 have already been associated with PDAC, however, their validation using immunoblotting proved challenging. This is probably due to extensive PTMs and processing thus indicating the need for raising specific antibodies for urinary proteins. Despite this, our study clearly demonstrates that urine is a valid source of noninvasive biomarkers in patients with pancreatic diseases.

Pancreatic Expression database: a generic model for the organization, integration and mining of complex cancer datasets.

BACKGROUND: Pancreatic cancer is the 5th leading cause of cancer death in both males and females. In recent years, a wealth of gene and protein expression studies have been published broadening our understanding of pancreatic cancer biology. Due to the explosive growth in publicly available data from multiple different sources it is becoming increasingly difficult for individual researchers to integrate these into their current research programmes. The Pancreatic Expression database, a generic web-based system, is aiming to close this gap by providing the research community with an open access tool, not only to mine currently available pancreatic cancer data sets but also to include their own data in the database. DESCRIPTION: Currently, the database holds 32 datasets comprising 7636 gene expression measurements extracted from 20 different published gene or protein expression studies from various pancreatic cancer types, pancreatic precursor lesions (PanINs) and chronic pancreatitis. The pancreatic data are stored in a data management system based on the BioMart technology alongside the human genome gene and protein annotations, sequence, homologue, SNP and antibody data. Interrogation of the database can be achieved through both a web-based query interface and through web services using combined criteria from pancreatic (disease stages, regulation, differential expression, expression, platform technology, publication) and/or public data (antibodies, genomic region, gene-related accessions, ontology, expression patterns, multi-species comparisons, protein data, SNPs). Thus, our database enables connections between otherwise disparate data sources and allows relatively simple navigation between all data types and annotations. CONCLUSION: The database structure and content provides a powerful and high-speed data-mining tool for cancer research. It can be used for target discovery i.e. of biomarkers from body fluids, identification and analysis of genes associated with the progression of cancer, cross-platform meta-analysis, SNP selection for pancreatic cancer association studies, cancer gene promoter analysis as well as mining cancer ontology information. The data model is generic and can be easily extended and applied to other types of cancer. The database is available online with no restrictions for the scientific community at http://www.pancreasexpression.org/.

Post traumatic intra thoracic spleen presenting with upper GI bleed!--a case report.

BACKGROUND: Isolated splenic vein thrombosis with left sided portal hypertension is a rare cause of upper gastrointestinal bleed. Diagnosis is difficult and requires a high index of suspicion, especially in patients presenting with gastrointestinal bleed in the presence of splenomegaly and normal liver function tests. CASE PRESENTATION: A 64 year old male presented with haematemesis and melaena. An upper gastrointestinal endoscopy revealed the presence of antral erosions in the stomach and fundal varices. A computerised tomography scan of abdomen confirmed the presence of a diaphragmatic tear and the spleen to be lying in the left hemi thorax. The appearances of the splenic vein on the scan were consistent with thrombosis. CONCLUSION: Left sided portal hypertension as a result of isolated splenic vein thrombosis secondary to trauma is rare. The unusual presentation of our case, splenic herniation into the left hemithorax, causing fundal varices leading to upper gastrointestinal bleed 28 years after the penetrating injury, makes this case most interesting. We believe that this has not been reported in literature before.

Deep femoral artery aneurysm: Report of a case.

Aneurysms involving the deep femoral artery, otherwise known as the profunda femoris artery (PFA), are extremely rare. Rarer still are bilateral PFA aneurysms (PFAAs). The diagnosis is difficult, but it may be suggested by the presence of a pulsatile tumor in the region of the femoral artery or by symptoms resulting from complications such as rupture or thromboembolism. A high index of suspicion is essential to diagnose them because they may present atypically. Surgery remains the treatment of choice and should be carried out electively for asymptomatic aneurysms. Surgery in an emergency situation can be challenging, especially when it involves vascular reconstruction as dictated by the peripheral vascular circulation.