International Study Group Research Articles

Histopathological tumour response scoring in resected pancreatic cancer following neoadjuvant therapy: international interobserver study (ISGPP-1).

Most tumour response scoring systems for resected pancreatic cancer after neoadjuvant therapy score tumour regression. However, whether treatment-induced changes, including tumour regression, can be identified reliably on haematoxylin and eosin-stained slides remains unclear. Moreover, no large study of the interobserver agreement of current tumour response scoring systems for pancreatic cancer exists. This study aimed to investigate whether gastrointestinal/pancreatic pathologists can reliably identify treatment effect on tumour by histology, and to determine the interobserver agreement for current tumour response scoring systems. Overall, 23 gastrointestinal/pancreatic pathologists reviewed digital haematoxylin and eosin-stained slides of pancreatic cancer or treated tumour bed. The accuracy in identifying the treatment effect was investigated in 60 patients (30 treatment-naive, 30 after neoadjuvant therapy (NAT)). The interobserver agreement for the College of American Pathologists (CAP) and MD Anderson Cancer Center (MDACC) tumour response scoring systems was assessed in 50 patients using intraclass correlation coefficients (ICCs). An ICC value below 0.50 indicated poor reliability, 0.50 or more and less than 0.75 indicated moderate reliability, 0.75 or more and below 0.90 indicated good reliability, and above 0.90 indicated excellent reliability. The sensitivity and specificity for identifying NAT effect were 76.2 and 49.0 per cent respectively. After NAT in 50 patients, ICC values for both tumour response scoring systems were moderate: 0.66 for CAP and 0.71 for MDACC. Identification of the effect of NAT in resected pancreatic cancer proved unreliable, and interobserver agreement for the current tumour response scoring systems was suboptimal. These findings support the recently published International Study Group of Pancreatic Pathologists recommendations to score residual tumour burden rather than tumour regression after NAT.

Compliance with preventive measures recommended by an international study group for pressure injuries in adult critically ill patients.

The objective of this cross-sectional descriptive study is to analyse the degree of compliance with the preventive measures for pressure injuries reported by an International Study Group in a cohort of adult critically ill patients. The level of risk of developing pressure injuries was determined using the Conscious level, Mobility, Hemodynamics, Oxygenation and Nutrition (COMHON) index. According to the level of risk, the preventive measures applied to each patient and scores on the different components of the index were recorded. Number, location and degree of pressure injuries were registered. Seventy-three patients (male: 68%) with an acute physiology and chronic health evaluation (APACHE) II: 12,1 ± 6,2 and 56,1% of them with invasive mechanical ventilation. The prevalence of pressure injuries was 21,9%, with 43,7% of sacral location and 75% of grade II. The level of risk using the COMHON index was distributed between low 30,1%, intermediate 23,3% and high 46,6%. The compliance range from 0% (offloading heel devices) to the use of active mattress and incontinence pads (100%). Regarding repositioning the degree of compliance varies (from 20% to 80%) according if patients with contraindications (4 points in subscale of Mobility) or those with the capacity to mobilise themselves (2 points in subscale of Mobility) are included in the denominator. We have found that in our ICU there is a wide range of compliance with the use of the preventive measures recommended by the International Study Group. Some of them are related not by the general score of the COMHON scale, but to that obtained in its subscale components.

Pediatric Behçet's disease: Experience of a single tertiary center.

The aim of this study was to examine the clinical and phenotypic features of pediatric Behçet's disease (PEDBD) in our clinic and present the rates of fulfilling the diagnostic criteria. Thirty-four patients (20 males, 14 females; mean age: 16.0±2.1 years; range, 10 to 18 years) diagnosed with PEDBD between January 2010 and December 2019 were retrospectively evaluated. Patients were reclassified according to 1990 International Study Group (ISG) criteria, 2014 International Criteria for Behçet's Disease (ICBD), and PEDBD criteria. The mean age at diagnosis was 12.6±3.1 years, the median diagnosis delay time was 12.0 (range, 4.5 to 27.0) months, and the mean age at symptom onset was 10.8±2.9 years. The mean follow-up period was 31.9±20.9 months. Oral aphthous ulcer was observed in 33 (97.1%), genital ulcer in 16 (47.0%), ocular involvement in 15 (44.1%), skin lesion in 11 (32.3%), joint involvement in nine (26.4%), both vascular and neurological involvement in six (17.6%) patients. The pathergy test was positive in 11 (37.8%) patients, and human leukocyte antigen (HLA)-B51 was positive in 11 (78.5%) of 14 patients. The rates of patients meeting the criteria for ISG, ICBD, and PEDBD were 52.9%, 82.4%, and 50.0%, respectively. Pathergy and HLA-B51 can be used as supportive findings in patients who do not meet the diagnostic criteria. However, expert opinion is still the gold standard in diagnosis.

Rationale and design of the peripheral nerve tumor registry: an observational cohort study

ABSTRACT Aim Peripheral nerve tumors (PNT) are rare lesions. To date, no systematic multicenter studies on epidemiology, clinical symptoms, treatment strategies and outcomes, genetic and histopathologic features, as well as imaging characteristics of PNT were published. The main goal of our PNT Registry is the systematic multicenter investigation to improve our understanding of PNT and to assist future interventional studies in establishing hypotheses, determining potential endpoints, and assessing treatment efficacy. Methods Aims of the PNT registry were set at the 2015 Meeting of the Section of Peripheral Nerve Surgery of the German Society of Neurosurgery. A study protocol was developed by specialists in PNT care. A minimal data set on clinical status, treatment types and outcomes is reported by each participating center at initial contact with the patient and after 1 year, 2 years, and 5 years. Since the study is coordinated by the Charité Berlin, the PNR Registry was approved by the Charité ethics committee (EA4/058/17) and registered with the German Trials Registry (www.drks.de). On a national level, patient inclusion began in June 2016. The registry was rolled out across Europe at the 2019 meeting of the European Association of Neurosurgery in Dublin. Results Patient recruitment has been initiated at 10 centers throughout Europe and 14 additional centers are currently applying for local ethics approval. Conclusion To date, the PNT registry has grown into an international study group with regular scientific and clinical exchange awaiting the first results of the retrospective study arm.

58 Comparison of the 2015 pediatric diagnostic criteria for Behcet’s disease with the 2014 and 1990 International Study Group Diagnostic Criteria

BackgroundBehçet's disease is a multisystem vasculitis whose pathogenesis remains unclear. Although usually described in young adults, it may begin in childhood. The diagnosis is clinical, based on international criteria. The limitations of early diagnosis are related to the progressive onset of symptoms and the variety of differential diagnoses at this age in the absence of a pathognomonic diagnostic test.ObjectivesTo report the epidemiological features of our series and to compare the 2015 pediatric criteria with the 2014 and 1990 international criteria.Materials and MethodsThis is a monocentric, retrospective study of 31 children over an 11-year period from January 2011 to December 2021. All patients suspected with Behcet's disease by a pediatric rheumatologist were included in the study, the 2014 international criteria “ISG 2014” being the gold standard classification criteria used in our center.Results31 cases of Behcet's were collected. The mean age was 10 years (5.5–16) ± 2.87 years. A female predominance is noted with a sex ratio F/M of 1.21. A quarter of the patients were from a consanguineous marriage and 38.7% had a family history of Behcet disease. Mucocutaneous manifestations were represented by recurrent oral aphthosis 87.1%, genital aphthosis 29%, pseudofolliculitis 48.4%, erythema nodosum 6.5% and acne lesions 3.2%. The pathergy test was positive in 1 case. Ocular involvement was reported in 29% and joint involvement in 45.2%. Thromboembolic complication was seen in 9.6% and neurobehcet in one patient. The HLA B51 antigen was present in 45.2% of cases. In our series 38.7% respond the pediatric criteria, while 61.3% met the 2014 international criteria and 35.5% met the 1990 international criteria. The 2015 pediatric criteria have respectively a sensitivity and specificity of 63.2% and 100% (p = 0.002) compared with the 2014 international criteria taken as gold standard, as well as the 1990 international criteria with a respective sensitivity and specificity of 52.6% and 91.7% (p = 0.034).ConclusionOur study highlights a female predominance, a high rate of consanguinity and familial Behcet. The sensitivity and specificity of the 1990 pediatric and international criteria appear to be better than those of 2014, with a more significant trend for the 2015 pediatric criteria (p = 0.002).

Appraising pancreatic fistula in pancreas transplantation: A comprehensive complication index based analysis of postoperative outcomes and predictors of graft survival

BackgroundA definition of pancreatic fistula specifically addressing pancreas transplantation (PT) is lacking. This study sought to characterize pancreatic fistula in this setting and to define its clinical relevance on the postoperative course and long-term graft survival (GS). MethodsConsecutive simultaneous pancreas and kidney transplantations were analysed. The global postoperative course was assessed through the comprehensive complication index (CCI). PF was defined according to the original International Study Group for Pancreatic Surgery (ISGPS) definition. Predictors of poor postoperative course and GS were explored. ResultsSeventy-eight patients were analysed. Surgical morbidity was 48.7%, with severe complications occurring in 39.7%. Ninety-day mortality was 2.6%. PF occurred in 56.6% of patients, although its average clinical burden was low and did not correlate with either early or long-term outcomes. Peri-graft fluid collections, postoperative day (POD) 1 drain fluid amylase (DFA) ≥ 2200 U/L, and POD 5 DFA/serum amylase ratio ≥7.0 independently correlated with poor postoperative course. Perigraft fluid collections were associated with reduced GS. ConclusionConventionally defined pancreatic fistula is frequent following PT, although its clinical impact is negligible. To define clinically relevant PF, novel cut-offs for DFA might be pondered in a future series, while perigraft fluid collections should be strongly considered.

Prognostic impact of plasma level of NT-pro BNP in patients with microvascular angina – a report from the international cohort study by COVADIS

Abstract Aims Although the importance of microvascular angina (MVA) has been emerging, prognostic biomarkers for MVA remain to be developed. We thus aimed to examine whether plasma level of N-terminal prohormone of brain natriuretic peptide (NT-pro BNP) could predict the prognosis of MVA patients. Methods In the international prospective cohort study of MVA patients by the Coronary Vasomotor Disorders International Study (COVADIS) group, we evaluated the association between plasma level of NT-pro BNP and the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. Results We examined a total of 226 MVA patients (M/F 66/160, 61.9±10.2 [SD] years) with both plasma NT-pro BNP levels and echocardiographic data in the COVADIS study. Plasma NT-pro BNP level was elevated (median 94 pg/ml, IQR 45–190) while mean LVEF (69.2±10.9%) and E/e' (10.7±5.2) were almost normal. During follow-up period of a median of 365 days (IQR 365–482), 29 MACEs occurred. ROC curve analysis identified plasma NT-pro BNP level of 78 pg/ml as the optimal cut-off value. Multivariable logistic regression analysis revealed that plasma NT-pro BNP level ≥78 pg/ml significantly correlated with the incidence of MACE (odds ratio (OR) [95% confidence interval (CI)] 3.11 [1.14–8.49], P=0.03). When divided into 2 groups by NT-pro BNP 78 pg/ml, the Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with NT-pro BNP ≥78 (log lank, P=0.03) (Figure). Conclusions These results indicate that plasma NT-pro BNP level is a novel prognostic biomarker for MVA patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Japan Heart Foundation

Post-occlusive reactive hyperaemia can objectify the occurrence of vasospasm induced ischemia during acetylcholine provocation testing

Abstract Introduction Acetylcholine (ACh) spasm provocation testing together with the diagnostic criteria published by the Coronary Vasomotor Disorders International Study Group (COVADIS) are considered the gold standard for the diagnosis of coronary vasospasm in contemporary clinical practice. In 20–29% of patients undergoing vasospasm provocation an equivocal test result occurs when these criteria are only partially met and poses a diagnostic dilemma. Post-occlusive reactive hyperaemia is a marker of acute myocardial ischemia and could serve as an added objective diagnostic criterium for the diagnosis of acetylcholine induced vasospasm. Purpose The aim of this study is therefore to evaluate the occurrence of post-occlusive reactive hyperaemia in the equivocal, positive and negative test result that follows acetylcholine vasospasm provocation. Methods 66 patients with angina and non-obstructive coronary artery disease on angiography (ANOCA) who underwent the entire ACh spasm provocation testing protocol were included in this analysis. After each ACh dose angiography was performed and when vasospasm occurred 200 μg nitro-glycerine was administered intracoronary. Definitions and diagnostic criteria for CAS were in line with those used by the COVADIS working group to diagnose epicardial and microvascular vasospasm. An equivocal test result was defined as the induction of recognisable angina without ischemic ECG changes, in reaction to ACh. Doppler flow was continuously measured during the procedure. Changes in flow due to ACh mediated vasodilation quickly return to baseline values due to its short-half life. Therefore, the occurrence of post-ischemic reactive hyperaemia was assessed by the extended time to return to baseline flow, the so called “flow recovery time”. Results We analysed the flow recovery time in 21 patients with epicardial vasospasm, in 16 with microvascular spasm, in 14 with an equivocal test result and in 15 with a negative test result. Mean age of the entire study population was 56±11 years and 86% were female. In reaction to dose 1 to 3 flow recovery time was similar between all diagnostic endotypes. In reaction to the fourth dose flow recovery time was extended in the epicardial, microvascular and equivocal test result compared to the negative test result indicative of post-ischemic reactive hyperaemia. Conclusion Post-occlusive reactive hyperaemia occurs in patients with an equivocal test result similar to patients with microvascular vasospasm and epicardial vasospasm. These findings indicate the occurrence of acetylcholine induced vasospasm in the equivocal test result and these patients may benefit from medical treatment. Funding Acknowledgement Type of funding sources: None.

Intracapsular approach used in laparoscopic duodenum-preserving total pancreatic head resection for pancreatic headbenign orlow-grade malignanttumors.

Laparoscopic duodenum-preserving total pancreatic head resection (LDPPHRt) is used for treating benign orlow-grade malignanttumors of the pancreatic head. However, preservation of the duodenum and biliary tract integrity remains challenging. We present a new approach for LDPPHRt and evaluate its feasibility and safety. From April 2020 to December 2020, 30 patients successfully underwent LDPPHRt using the intracapsular approach in our center. Their medical records were reviewed for relevant clinical characteristics, pathologic findings, postoperative complications, and survival. The median diameter of the lesions was 3.6cm (range, 2.0-5.5cm). The median operative time was 234.7min (range, 195-310min). The median blood loss was 66.7ml (range, 20-250ml). The morbidity rate was 26.7%, including POPF, hemorrhage, lymphatic leakage, wound infection, pulmonary infection, and delayed gastric emptying. Five patients developed pancreatic fistula type A, and two patients had type B, classified according to the International Study Group on Pancreatic Fistula. No biliary tract injury or duodenal leakage was observed. The median postoperative hospital stay was 11.5days (range, 6-25), and the operative mortality rate was 0%. The intracapsular approach is a feasible and safe surgical procedure in LDPPHRt for patients with benign orlow-grade malignanttumors, especially those without severe pancreatic head fibrosis or peripancreatic adhesions.

Prophylactic abdominal drainage or no drainage after distal pancreatectomy (PANDORINA): a study protocol of a binational multicenter randomized controlled trial

BackgroundProphylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure.The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C.Methods/designBinational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality.DiscussionPANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente et al., 2007; Bassi et al., 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., 2016; Pratt et al., 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., 2022; Asbun and Stauffer, 2011).

Oncological outcomes of rectal cancer patients with anastomotic leakage: A multicenter case-control study.

IntroductionThis study aimed to evaluate the impact of anastomotic leakage (AL) on oncological outcomes after restorative rectal cancer surgery.MethodsPatients who underwent anterior resection for rectal adenocarcinoma between January 2011 and December 2017 were retrospectively reviewed. Data were collected from three colorectal surgery centers. Patients with grade B and C leaks according to the International Study Group of Rectal Cancer classification were identified and compared with the control group. Estimated recurrence and survival rates were compared using the log-rank method and Cox regression analysis.ResultsA total of 367 patients were included in the study, with a mean follow-up of 59.21 months. AL occurred in 64 patients (17.4%). Fifteen patients with AL (23.5%) developed local recurrence (LR) compared to 17 (4.8%) in the control group (p < 0.001). However, distant recurrence rates were similar (10.9% vs. 9.6%; p = 0.914) between the groups. Kaplan-Meier curves showed that patients with AL had a reduced 5-years local recurrence-free survival (96% vs. 78%, log-rank p < 0.001). AL (OR 4.576; 95% CI, 2.046–10.237; p < 0.001) and node involvement (OR 2.911; 95% CI, 1.240–6.835; p = 0.014) were significantly associated with LR in multivariate analysis. AL was significantly associated with DFS only at univariate analysis (HR 1.654; 95% CI: 1.024–2.672; p = 0.037), with a difference between 5-year DFS of patients with and without AL (71.6% vs. 86.4%, log-rank p = 0.04). Only male gender, pT3-4 stage, and node involvement were identified as independent prognostic factors for reduced DFS in the multivariate Cox regression analysis.ConclusionIn this cohort of patients, AL was associated with a significant risk of LR after rectal cancer surgery.

Modified Clavien-Dindo-Sink system is reliable for classifying complications following surgical treatment of early-onset scoliosis.

Appropriately measuring and classifying surgical complications is a critical component of research in vulnerable populations, including children with early-onset scoliosis (EOS). The purpose of this study was to assess the inter- and intra-rater reliability of a modified Clavien-Dindo-Sink system (CDS) classification system for EOS patients among a group of pediatric spinal deformity surgeons. Thirty case scenarios were developed and presented to experienced surgeons in an international spine study group. For each case, surgeons were asked to select a level of severity based on the modified CDS system to assess inter-rater reliability. The survey was administered on two occasions to allow for assessment of intra-rater reliability. Weighted Kappa values were calculated, with 0.61 to 0.80 considered substantial agreement and 0.81 to 1.00 considered nearly perfect agreement. 11/12 (91.7%) surgeons completed the first-round survey and 8/12 (66.7%) completed the second. Inter-observer weighted kappa values for the first and second survey were 0.75 [95% CI 0.56-0.94], indicating substantial agreement, and 0.84 [95% CI 0.70-0.98], indicating nearly perfect agreement, respectively. Intra-observer reliability was 0.86 (range 0.74-0.95) between the first and second surveys, indicating nearly perfect agreement . The modified CDS classification system demonstrated substantial to nearly perfect agreement between and within observers for the evaluation of complications following the surgical treatment of EOS patients. Adoption of this reliable classification system as a standard for reporting complications in EOS patients can be a valuable tool for future research endeavors, as we seek to ultimately improve surgical practices and patient outcomes. Level V.

Oncologic management of ampullary cancer: International survey among surgical and medical oncologists

BackgroundAmpullary adenocarcinoma (AAC) is a rare neoplasm which as a result is lacking specific treatment guidelines. This international survey study was performed to gain insight in the current daily practice of AAC. MethodsSurgeons and medical oncologists, whom were members of the Dutch Pancreatic Cancer Group, International Study Group on Ampullary Cancer, International Hepato-Pancreato-Biliary Association, European and International Consortium on Minimally Invasive Pancreatic Surgery, or contributed to (peri)ampullary cancer research, were invited through email and newsletters between January and October 2021. ResultsOverall, 217 surgeons and medical oncologists completed the survey. Most of the respondents work in Europe (60%), and in a pancreatic expertise center (86%). The majority of respondents (87%) stated that the histological AAC subtype (e.g. intestinal vs. pancreatobiliary) was determined in the resection specimen. Neoadjuvant treatment for resectable disease was considered by 24% and adjuvant therapy by 90% of the respondents, with 80% of them choosing adjuvant chemotherapy alone. The formation of multidisciplinary teams, improvement in resection procedures, increased availability of chemotherapy regimens, and increased knowledge on tumor biology were considered as the most important developments in the last five years. The necessity for randomized controlled trials was mentioned by 50% of the respondents. ConclusionsThis international survey highlights the existing variation in the management of patients with AAC, especially regarding the use of (neo)adjuvant therapy. More data from trials and international registries are needed to develop evidence-based guidelines on surgical and oncological management with the ultimate aim to improve outcomes for patients with AAC.

Is the analogue cognitive test from the ISPOCD equivalent to the digital cognitive test Mindmore? A protocol for a randomised cross-over study including qualitative interviews with self-reported healthy seniors

IntroductionPostoperative cognitive decline affects cognitive domains such as executive functions, memory, concentration and information processing. The analogue neuropsychological test developed by the International Study Group of Postoperative Cognitive Dysfunction (ISPOCD)...

Effect of postoperative administration of nafamostat mesilate on posthepatectomy liver failure

To investigate whether the administration of nafamostat mesilate (NM) reduces the risk of posthepatectomy liver failure (PHLF) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). We retrospectively reviewed the 1114 patients who underwent hepatectomy for HCC between 2004 and 2020. NM was selectively administered to patients undergoing major hepatectomy with an estimated blood loss of >500mL. NM group was administered via intravenous of 20mg of NM from immediately after surgery until postoperative day 4. We performed 1:1 propensity score matching and included 56 patients in each group. PHLF was defined according to the International Study Group of Liver Surgery (ISGLS). The incidence of PHLF was lower in the NM group than control group (P=0.018). The mean peak total bilirubin (P=0.006), aspartate transaminase (P=0.018), and alanine aminotransferase (P=0.018) levels postoperatively were significantly lower in the NM group. The mean hospital stays (P=0.012) and major complication rate (P=0.023) were also significantly lower in the NM group. Prophylactic administration of NM reduced the risks of complication and decreased the frequency of PHLF after hepatectomy. A further prospective study is needed to verify our findings.

Role of inflammatory and nutritional markers in predicting complications after pancreaticoduodenectomy

BackgroundPancreaticoduodenectomy is associated with considerable morbidity and mortality rates. Early recognition of patients likely to develop severe postoperative complications will allow the timely commencement of a tailored approach. This study aimed to predict postoperative complications using inflammatory and nutritional markers measured early in the postoperative period. MethodsPatients who underwent pancreaticoduodenectomy between June 2019 and November 2020 were included in the study. Postoperative pancreatic fistula, delayed gastric emptying, and postoperative pancreatic hemorrhage were graded according to the International Study Group of Pancreatic Fistula and the International Study Group of Pancreatic Surgery. We also documented other complications such as wound infection, intra-abdominal collection, and nonsurgical complications. Nutritional and inflammatory markers were analyzed on postoperative days 1 and 3. Patients were followed up for 30 days or until discharge, depending on which was longer. ResultsOf the 58 enrolled patients, 51 were included in the study. The incidence of postoperative pancreatic fistula was 51% (clinically relevant postoperative pancreatic fistula 27.4%), delayed gastric emptying was 80.4% (clinically relevant delayed gastric emptying 43%), postoperative pancreatic hemorrhage was 3.9%, intra-abdominal collection was 23.5%, and wound infection was 29.4%. The median drain fluid interlukin-6 levels on postoperative day 1 and postoperative day 3 were significantly higher in patients developing clinically relevant postoperative pancreatic fistula than in those who did not develop clinically relevant postoperative pancreatic fistula on postoperative day 1 (211 [125, 425] fg/dL vs 99 [15, 170] fg/dL, [P = .045]) and on postoperative day 3 (110 [22, 28] fg/dL vs 10 [1.8, 45] fg/dL [P = .002]). Patients who tested negative for urine trypsinogen-2 on postoperative day 3 had a significantly lower probability of developing clinically relevant postoperative pancreatic fistula than those who tested positive (1 vs 24 [P < .001]). A model comprising both drain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 definitively ruled out the occurrence of clinically relevant postoperative pancreatic fistula. ConclusionDrain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 ruled out the occurrence of clinically relevant postoperative pancreatic fistula.

Characterisation of circulating endothelial microparticles in Behçet's disease: new markers of chronic endothelial damage?

Endothelial cell-derived microparticles (EMPs) are directly indicative of endothelial cell activation or apoptosis, and may also reflect endothelial inflammation, increased coagulation, and vascular tone. The aim of this study is to investigate whether EMPs would be able to evaluate system involvement and be a new indicators of disease activity in Behçet's disease (BD). Thirty-nine consecutive BD patients (who fulfilled the modified 1990 International Study Group on Behçet's disease or the 2006 International Criteria for Behçet's Disease) and 30 age- and sex-matched healthy controls were enrolled. The plasma levels of EMPs were measured by flow cytometry utilising specific labels for endothelial MPs (CD31+ and CD42b-). The levels of circulating EMPs (CD31+ and CD42b-) were significantly elevated in the case group compared with the healthy control group (p =0.000). Moreover, BD patients plasma EMPs were positively correlated with BD current activity form (r=0.802, p =0.000). Vascular and gastrointestinal involvement in BD patients were significantly increased (p=0.004 and p=0.011, respectively) with respect to patients without vascular and gastrointestinal EMPs. Levels of circulating EMPs are elevated in BD patients and correlate with the disease activity; the elevated EMPs may be a potential indicator to predict disease activity of BD. The plasma level of EMPs was increased, which indicated the increased risk of vascular and digestive tract involvement in BD.

Development and external validation of DISPAIR fistula risk score for clinically relevant postoperative pancreatic fistula risk after distal pancreatectomy.

Highly utilized risk scores for clinically relevant postoperative pancreatic fistula (CR-POPF) have guided clinical decision-making in pancreatoduodenectomy. However, none has been successfully developed for distal pancreatectomy. This study aimed to develop and validate a new fistula risk score for distal pancreatectomy. Patients undergoing distal pancreatectomy at Helsinki University Hospital, Finland from 2013 to 2021, and at Karolinska University Hospital, Sweden, from 2010 to 2020, were included retrospectively. The outcome was CR-POPF, according to the 2016 International Study Group of Pancreatic Surgery definition. Preoperative clinical demographics and radiological parameters such as pancreatic thickness and duct diameter were measured. A logistic regression model was developed, internally validated with bootstrapping, and the performance assessed in an external validation cohort. Of 668 patients from Helsinki (266) and Stockholm (402), 173 (25.9 per cent) developed CR-POPF. The final model consisted of three variables assessed before surgery: transection site (neck versus body/tail), pancreatic thickness at transection site, and diabetes. The model had an area under the receiver operating characteristic curve (AUROC) of 0.904 (95 per cent c.i. 0.855 to 0.949) after internal validation, and 0.798 (0.748 to 0.848) after external validation. The calibration slope and intercept on external validation were 0.719 and 0.192 respectively. Four risk groups were defined in the validation cohort for clinical applicability: low (below 5 per cent), moderate (at least 5 but below 30 per cent), high (at least 30 but below 75 per cent), and extreme (75 per cent or more). The incidences in these groups were 8.7 per cent (11 of 126), 22.0 per cent (36 of 164), 63 per cent (57 of 91), and 81 per cent (17 of 21) respectively. The DISPAIR score after distal pancreatectomy may guide decision-making and allow a risk-adjusted outcome comparison for CR-POPF.

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Haemodynamic characterisation of different endotypes in coronary artery vasospasm in reaction to acetylcholine.

Vasoreactivity testing with high-dose acetylcholine is considered vasospasm provocation and low-dose as endothelial function testing. To assess the changes in reaction to low- and high-dose acetylcholine in the endotypes of CAS as defined by the Coronary Vasomotor Disorders International Study Group (COVADIS) working group. Changes in coronary epicardial diameter, coronary blood flow (CBF) and vascular resistance were determined at low-dose acetylcholine. A total of 88 ANOCA patients were included in this analysis. In the negative group (n=14) incremental infusion of acetylcholine produced a progressive increase in CBF (p=0.008). In reaction to low-dose acetylcholine, the epicardial vasospasm group (n=30) is characterised by epicardial vasoconstriction that is significantly more severe compared to the microvascular vasospasm group (p=0.004)(n=23). The equivocal group (n=21) is characterised by an increase in CBF and reduction in vascular resistance that are both significantly different compared to the epicardial vasospasm group (p=0.036 and p=0.007, respectively). High-dose acetylcholine decreased epicardial diameter and CBF significantly in the epicardial vasospasm, microvascular vasospasm and in the equivocal group (all p<0.05. Vascular resistance increased significantly in the epicardial vasospasm group (p<0.001) and equivocal group (p=0.009). In reaction to low-dose acetylcholine the negative and equivocal endotype has haemodynamic changes that suggest intact endothelium. In reaction to high-dose acetylcholine the epicardial vasospasm, microvascular vasospasm and equivocal endotype have hemodynamic changes that suggest VSMC-hyperreactivity. These results suggest that the equivocal endotype is a positive test comparable to microvascular vasospasm in the presence of normal endothelial function.