PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Background: Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods: All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results: A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion: Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions

Positive Evolutionary Selection of an HD Motif on Alzheimer Precursor Protein Orthologues Suggests a Functional Role

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the “transcription binding site turnover.” CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

Early laparoendoscopic rendezvous for acute biliary pancreatitis: preliminary results.

INTRODUCTION: Early restored patency of the papilla has been hypothesized to reduce complications and mortality of acute biliary pancreatitis. The aim of this study was to evaluate the role of urgent laparoscopic cholecystectomy with intraoperative cholangiography and rendezvous when necessary in acute biliary pancreatitis natural history. PATIENTS AND METHODS: Patients observed in the early stage of an acute biliary pancreatitis were included in the study. Operative risk assessment based on American Society of Anesthesiologists (ASA) score allowed the performance of urgent laparoscopic cholecystectomy within 72 h from onset of symptoms in 55 patients and a delayed intervention during the same admission in 21 patients. Intraoperative cholangiography was performed in all cases, and clearance of common bile duct was performed by flushing when possible, or rendezvous when necessary. Evolution of pancreatitis was evaluated with clinical and radiological monitoring. RESULTS: Urgent laparoscopic cholecystectomy was performed in all cases without conversion. At intraoperative cholangiography common bile duct was free in 25 patients, a papillary spasm was observed in 9, and common bile duct stones in 21 patients. Patency of the papilla was restored by flushing in 13 patients, while a rendezvous was necessary in 17 patients. The rate of organ failure and pancreatic necrosis was 1.8%, overall mortality was 1.8%, and overall morbidity 21.8%. No infectious complications of peripancreatic collections were observed. CONCLUSION: Urgent laparoscopic cholecystectomy with selective intraoperative rendezvous may be considered as a treatment option in the early stage of acute biliary pancreatitis

Approccio diagnostico alle occlusioni ileali non neoplastiche.

Approccio diagnostico alle occlusioni ileali non neoplastiche

Tumor site and perigastric nodal status are the most important predictors of para-aortic nodal involvement in advanced gastric cancer.

BACKGROUND: This study was designed to identify pathological predictors of para-aortic nodal invasion in advanced gastric cancer. METHODS: Between 1990 and 2007, 294 patients with advanced gastric cancer underwent gastrectomy with D2 lymphadenectomy + para-aortic nodal dissection in Siena and Verona, Italy. RESULTS: Forty-seven (16%) patients had para-aortic node metastases. Of these, 91%, 88%, and 74%, respectively, also had metastases at stations No. 3, No. 1, and No. 7. Para-aortic node metastases were never observed when stations No. 1 and No. 3 were both negative. Patients were divided into three groups, according to the risk of para-aortic node invasion: (1) high-risk group (n = 24, 8.2%), presenting a 42% risk and comprising T3/T4 cancers with mixed/nonintestinal histology, arising from the upper third; (2) low-risk group (n = 138, 46.9%), presenting a 0-10% risk and including middle-lower third tumors-either T2 irrespective of histology, or T3/T4 with intestinal histology; (3) intermediate-risk group, comprising all other patients (n = 132, 44.9%). Their risk ranged between 16% and 30%, but increased up to 21-37.5% after excluding 33 patients with negative No. 1 and No. 3 stations. CONCLUSIONS: The combination of tumor site, histology, and T stage with perigastric nodal status allowed identification of patients at higher risk of para-aortic nodal invasion who could benefit from para-aortic nodal dissection

TNFR-Associated Factor-2 (TRAF2): Not only a Trimer

TNF receptor-associated factors (TRAFs) are characterized by an oligomeric structure that plays a fundamental role in the binding process with membrane receptors. In this work, we studied the trimer-to-monomer (T ↔ 3M) equilibrium transition of the TRAF2 C-terminal domain using both chemical (dilution/guanidinium hydrochloride) and mechanical stress (high pressure) to induce the dissociation of the native protein into subunits. The experimental results and computer simulations indicate that stable monomers exist and that their population accounts for 15% of the total TRAF2 molecules already at a physiological intracellular concentration (≈1 μM), being instead the predominant species in the nanomolar concentration range. Because the total amount of TRAF2 changes during a cell cycle, the monomer-trimer equilibrium can be crucial for regulating the activities of TRAF2 in vivo

Chemoradiotherapy followed by surgery for squamous cell carcinoma of the thoracic esophagus with clinical evidence of adjacent organ invasion.

Background: The role of surgery for esophageal squamous cell carcinoma (SCC)with clinical evidence of adjacent organ invasion (cT4) is a debated issue. This study was aimed at analyzing our experience with chemoradiotherapy (CRT) followed by surgery as treatment for non-metastatic cT4 SCC of the thoracic esophagus. Methods: The results of 51 patients consecutively treated at the First Department of General Surgery, University of Verona, from January 1987 to December 2004 were analyzed. Results: The most frequently clinically involved structures were the trachea (43.1%),the main left bronchus (17.6%), and the thoracic aorta (15.7%). CRT was completed in all but one of the patients (98.0%) without toxicity-related deaths. After completion of induction treatment 49 patients underwent surgery (96.1%), and resection was possible in 40 patients (78.4%) but R0 surgery was rarely obtained (39.2%).Pathologic downstaging was achieved in 18 cases (35.3%) while a major response(responders) was observed in 10 patients (19.6%) and a complete response (pT0N0) in7 (13.7%). The overall median survival time was 11.1 months with a 3-year survival rate of 8.8%. A signi\ufb01cantly better survival (P &lt; 0.001) was observed after a R0 resection (median: 22.3 months; 3-year survival: 25.4%; P &lt; 0.001) and for responders (median: 33.1 months; 3-year survival: 25.7%; P \ubc 0.019). Conclusions: Aggressive multi-modal therapy with CRT followed by surgery in cT4SCC of the thoracic esophagus is feasible. Surgery should be limited to patients with signi\ufb01cant response to induction treatment and a high probability of R0 resection