Prospective multicentre study of indications for surgery in patients with idiopathic acute pancreatitis following endoscopic ultrasonography (PICUS).

BACKGROUND: Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP). METHODS: This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up. RESULTS: After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life. CONCLUSION: EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study.

Some patients develop acute inflammation of the pancreas without a clear cause. These patients have a high risk of developing more episodes of acute inflammation of the pancreas. Potentially, such inflammation could be caused by tiny gallstones that physicians are not able to detect. If this is true, these patients may also benefit from surgical removal of the gallbladder. However, this is still controversial. Endoscopic ultrasonography is a diagnostic procedure during which a physician looks at the gallbladder and bile ducts in detail via a small ultrasound probe inserted through the mouth. This endoscopic ultrasonography may be able to detect gallstones better than physicians were able to previously. This study tested the value of endoscopic ultrasonography, and the number of patients who developed more episodes of acute inflammation after endoscopic ultrasonography was recorded. Some 106 patients with acute inflammation of the pancreas for the first time without a clear cause participated and were offered endoscopic ultrasonography. The number of times endoscopic ultrasonography found a cause for the acute inflammation was recorded, as well as safety parameters, number of patients who developed more episodes of acute inflammation, and quality of life. After screening 957 patients, 105 ultimately underwent endoscopic ultrasonography. A cause was found in one-third of patients. This was mostly (tiny) gallstones, but chronic inflammation and even tumours were found. These patients were mostly treated surgically for their gallstones and tumours. In the first year after the first acute episode of inflammation, the inflammation came back at least once in almost one in six patients in whom endoscopic ultrasonography did not find a cause. This occurred less in patients in whom a cause was found; the inflammation came back in 1 in 16 of these patients. It was also found that having inflammation coming back negatively affected quality of life. In this study, endoscopic ultrasonography was able to detect a cause in one-third of patients with first-time acute inflammation of the pancreas. In one in four patients, this cause could be treated by a surgical procedure. Whether surgical removal of the gallbladder can be helpful in patients in whom endoscopic ultrasonography is not able to detect an aetiology should be investigated in further studies.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. MAIN BODY: This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. CONCLUSION: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field, and include new PET-labelling methods for 11C and 18F, the importance of choosing the proper chelator for a given radioactive metal ion, implications of total body PET on use of radiopharmaceuticals, legislation issues and radionuclide therapy including the emerging role of 161Tb.

Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses; a multi-center prospective cross sectional study.

BACKGROUND: The diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions. METHODS: In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively. RESULTS: In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%. INTERPRETATION: This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integration of NGS results can prevent repeated EUS/FNA, and can also rigorously change the final diagnosis and treatment plan.

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis.

OBJECTIVE: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. DESIGN: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. RESULTS: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention-5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121). CONCLUSION: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.

An Explorative Study of the Incidental High Renal Excretion of [18F]PSMA-1007 for Prostate Cancer PET/CT Imaging.

Positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) allows for accurate diagnosis and staging of prostate cancer (PCa). Compared to other PSMA PET tracers available, [18F]PSMA-1007 is predominantly excreted via the hepatobiliary tract resulting in low renal excretion which improves evaluation of the pelvic area. However, some patients do show high urinary uptake of [18F]PSMA-1007. The present study aimed to investigate this sudden high urinary uptake of [18F]PSMA-1007 by evaluating [18F]PSMA-1007 PET scans from PCa patients. In this single-center retrospective study, patients that underwent [18F]PSMA-1007 PET imaging between July 2018 and January 2021 were included. Data regarding the individual patient characteristics, scan acquisition and batch production were analyzed. To determine the urinary excretion of [18F]PSMA-1007, a region of interest was drawn in the bladder, and standardized uptake values (SUVs) were calculated and compared to SUVs in the prostate. An SUVmax of >10 was considered high urinary excretion, an SUVmax 7.5−10 intermediate and an SUVmax < 7.5 low urinary excretion. A total of 344 patients underwent [18F]PSMA-1007 PET/CT imaging, with 37 patients receiving three or more [18F]PSMA-1007 PET/CT scans. The mean SUVmean and SUVmax of the bladder were 3.9 (SD 2.9) and 5.9 (SD 4.2), respectively. Fourteen percent of patients showed high urinary uptake of [18F]PSMA-1007. Twelve of the thirty-seven patients (32.4%) that had multiple scans showed a varying urinary uptake of [18F]PSMA-1007 per PSMA PET/CT scan. In terms of patient characteristics, risk factors, medication and blood laboratory results, no significant influencing variables were found. Nor was there a difference observed in the batch size and the mean radiochemical purity of PSMA-1007 for high- and low-excreting patients. However, the bladder volume affected the mean SUVmax in the bladder significantly, with higher SUVs in lower bladder volumes. In this study, we observed that a higher SUV in the urinary tract seemed to occur in patients with low bladder volume. A prospective study is needed to corroborate this hypothesis.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development. RESULTS: This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals and also a contribution in relation to MRI-agents is included. CONCLUSION: Trends in (radio)chemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.

Endoscopic full-thickness resection of T1 colorectal cancers: a retrospective analysis from a multicenter Dutch eFTR registry.

BACKGROUND: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC < 2 cm. We aimed to report clinical outcomes and short-term results. METHODS: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes. RESULTS: We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0 % (95 % confidence interval [CI] 82.7 %-90.3 %), 85.6 % (95 %CI 81.2 %-89.2 %), and 60.3 % (95 %CI 54.7 %-65.7 %). Curative resection rate was 23.7 % (95 %CI 15.9 %-33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %-70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological surgery was performed in 49/320 (15.3 %), with residual cancer in 11/49 (22.4 %). Endoscopic follow-up was available in 200/242 (82.6 %), with a median of 4 months and residual cancer in 1 (0.5 %) following an incomplete resection. CONCLUSIONS: eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes.

Hybrid endoscopic mucosal resection and full-thickness resection for large colonic polyps harboring a small focus of invasive cancer: a case series.

Endoscopic treatment of large laterally spreading tumors (LSTs) with a focus of submucosally invasive colorectal cancer (T1 CRC) can be challenging. We evaluated outcomes of a hybrid resection technique using piecemeal endoscopic mucosal resection (pEMR) and endoscopic full-thickness resection (eFTR) in patients with large colonic LSTs containing suspected T1 CRC. Six hybrid pEMR-eFTR procedures for T1 CRCs were registered in a nationwide eFTR registry between July 2015 and December 2019. In all cases, the invasive part of the lesion was successfully isolated with eFTR; with eFTR, histologically complete resection of the invasive part was achieved in 5 /6 patients (83.3 %). No adverse events occurred during or after the procedure. The median follow-up time was 10 months (range 6-27), with all patients having undergone ≥ 1 surveillance colonoscopy. One patient had a small adenomatous recurrence, which was removed endoscopically. In conclusion, hybrid pEMR-eFTR is a promising noninvasive treatment modality that seems feasible for a selected group of patients with large LSTs containing a small focus of T1 CRC.

Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module.

BACKGROUND: The translocator protein 18 kDa is recognised as an important biomarker for neuroinflammation due to its soaring expression in microglia. This process is common for various neurological disorders. DPA-714 is a potent TSPO-specific ligand which found its use in Positron Emission Tomography following substitution of fluorine-19 with fluorine-18, a positron-emitting radionuclide. [18F]DPA-714 enables visualisation of inflammatory processes in vivo non-invasively. Radiolabelling of this tracer is well described in literature, including validation for clinical use. Here, we report significant enhancements to the process which resulted in the design of a fully GMP-compliant robust synthesis of [18F]DPA-714 on a popular cassette-based system, Trasis AllinOne, boosting reliability, throughput, and introducing a significant degree of simplicity. RESULTS: [18F]DPA-714 was synthesised using the classic nucleophilic aliphatic substitution on a good leaving group, tosylate, with [18F]fluoride using tetraethylammonium bicarbonate in acetonitrile at 100∘C. The process was fully automated on a Trasis AllinOne synthesiser using an in-house designed cassette and sequence. With a relatively small precursor load of 4 mg, [18F]DPA-714 was obtained with consistently high radiochemical yields of 55-71% (n=6) and molar activities of 117-350 GBq/µmol at end of synthesis. With a single production batch, starting with 31-42 GBq of [18F]fluoride, between 13-20 GBq of the tracer can be produced, enabling multi-centre studies. CONCLUSION: To the best of our knowledge, the process presented herein is the most efficient [18F]DPA-714 synthesis, with advantageous GMP compliance. The use of a Trasis AllinOne synthesiser increases reliability and allows rapid training of production staff.

[Transpapillary gallbladder drainage with 'pigtail' stent]. / Transpapillaire galblaasdrainage met 'pigtail'-stent.

The transpapillary double 'pigtail' stent is placed endoscopically to drain the gallbladder after remission of a (recurrent) acute cholecystitis in patients with increased surgical risk. Technical success rate (placement of stent) is 83-88% and clinical success rate (remission of symptoms) is 80-93%. Although the procedure is effective, the stent is not commonly implemented. Possibly due to the challenging procedure or the introduction of the transgastric or transduodenic drainage with the Lumen Apposing Metal Stent (LAMS). This technique has a technical and clinical success rate of 94-95% and 90-97% respectively, significantly higher than the transpapillary stent. The LAMS can be placed during an acute cholecystitis. However, a cholecystectomy is contraindicated afterwards. Although the two procedures are complementary, future studies will tell if these two procedures will both continue to be used.

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study.

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered.

Endoscopic full-thickness resection (eFTR) of colorectal lesions: results from the Dutch colorectal eFTR registry.

BACKGROUND: Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions ≤ 30 mm unsuitable for conventional endoscopic resection. This study reports clinical outcomes from the Dutch colorectal eFTR registry. METHODS: Consecutive patients undergoing eFTR in 20 hospitals were prospectively included. The primary outcome was technical success, defined as macroscopic complete en bloc resection. Secondary outcomes were: clinical success, defined as tumor-free resection margins (R0 resection); full-thickness resection rate; and adverse events. RESULTS : Between July 2015 and October 2018, 367 procedures were included. Indications were difficult polyps (non-lifting sign and/or difficult location; n = 133), primary resection of suspected T1 colorectal cancer (CRC; n = 71), re-resection after incomplete resection of T1 CRC (n = 150), and subepithelial tumors (n = 13). Technical success was achieved in 308 procedures (83.9 %). In 21 procedures (5.7 %), eFTR was not performed because the lesion could not be reached or retracted into the cap. In the remaining 346 procedures, R0 resection was achieved in 285 (82.4 %) and full-thickness resection in 288 (83.2 %). The median diameter of resected specimens was 23 mm. Overall adverse event rate was 9.3 % (n = 34/367): 10 patients (2.7 %) required emergency surgery for five delayed and two immediate perforations and three cases of appendicitis. CONCLUSION : eFTR is an effective and relatively safe en bloc resection technique for complex colorectal lesions with the potential to avoid surgery. Further studies assessing the role of eFTR in early CRC treatment with long-term outcomes are needed.

Huntington's Disease: A Review of the Known PET Imaging Biomarkers and Targeting Radiotracers.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG expansion mutation in the huntingtin gene. As a result, intranuclear inclusions of mutant huntingtin protein are formed, which damage striatal medium spiny neurons (MSNs). A review of Positron Emission Tomography (PET) studies relating to HD was performed, including clinical and preclinical data. PET is a powerful tool for visualisation of the HD pathology by non-invasive imaging of specific radiopharmaceuticals, which provide a detailed molecular snapshot of complex mechanistic pathways within the brain. Nowadays, radiochemists are equipped with an impressive arsenal of radioligands to accurately recognise particular receptors of interest. These include key biomarkers of HD: adenosine, cannabinoid, dopaminergic and glutamateric receptors, microglial activation, phosphodiesterase 10 A and synaptic vesicle proteins. This review aims to provide a radiochemical picture of the recent developments in the field of HD PET, with significant attention devoted to radiosynthetic routes towards the tracers relevant to this disease.

Early Versus Standard Colonoscopy: A Randomized Controlled Trial in Patients With Acute Lower Gastrointestinal Bleeding: Results of the BLEED Study.

GOALS: The aim of our study was to examine differences in length of hospital stay (LOHS) between patients with lower gastrointestinal bleeding who received either an early colonoscopy (within 24 h of presentation) or a standard colonoscopy (within 1 to 3 d). BACKGROUND: Diagnostic management of lower gastrointestinal bleeding has been extensively debated in recent literature, especially whether colonoscopy within 24 hours of presentation is feasible and safe. STUDY: In this single center, nonblinded, randomized controlled trial, patients presenting at the emergency department with acute hematochezia were eligible if they required hospital admission. A total of 132 patients were included. Primary outcome was LOHS. Secondary outcomes included yield of colonoscopy, blood transfusion requirements, recurrent bleedings, complications, interventions related to complications, and 30-day mortality. The follow-up period was 1 month. RESULTS: In total, 63 patients were randomized for <24 hours colonoscopy and 69 for standard colonoscopy. In the intention to treat analysis, LOHS was significantly lower in patients that underwent an early colonoscopy, compared with the standard group: median 2.0 days (inter quartile range, 2.0 to 4.0) versus median 3.0 days (inter quartile range, 2.0 to 4.0) (P=0.009). Recurrent bleedings and hospital readmissions were significantly more frequent in the <24-hour group: 13% versus 3% (P=0.04) and 11% versus 2% (P=0.02), respectively. No difference was observed regarding the number of patients diagnosed with a confirmed or presumptive bleeding source. In both groups, blood transfusion rate was similar and 30-day mortality was 0. CONCLUSIONS: Early colonoscopy reduces LOHS, but also results in lower clinical efficacy compared with standard colonoscopy.

Acute Clinical Manifestation of Mesenteric Heterotopic Pancreatitis: A Pre- and Postoperative Confirmed Case.

Heterotopic pancreas is a relatively uncommon congenital anomaly, defined as pancreatic tissue in ectopic sites without an anatomic and vascular continuity with the main body of the pancreas. We report the case of a 58-year-old woman who was admitted to the hospital with the clinical suspicion of a mild, acute pancreatitis. Computed tomography, magnetic resonance imaging, transabdominal ultrasound, and endoscopic ultrasound revealed a normal orthotopic pancreas and the suspicion of a large heterotopic pancreas in the small bowel mesentery with signs of acute inflammation. The diagnosis of mesenteric heterotopic pancreatitis was preoperatively confirmed by endoscopic ultrasound-guided fine-needle aspiration and consequently histologically established after surgical resection.

Production of novel diagnostic radionuclides in small medical cyclotrons.

The global network of cyclotrons has expanded rapidly over the last decade. The bulk of its industrial potential is composed of small medical cyclotrons with a proton energy below 20 MeV for radionuclides production. This review focuses on the recent developments of novel medical radionuclides produced by cyclotrons in the energy range of 3 MeV to 20 MeV. The production of the following medical radionuclides will be described based on available literature sources: Tc-99 m, I-123, I-124, Zr-89, Cu-64, Ga-67, Ga-68, In-111, Y-86 and Sc-44. Remarkable developments in the production process have been observed in only some cases. More research is needed to make novel radionuclide cyclotron production available for the medical industry.

Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.

BACKGROUND: Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. METHODS/DESIGN: The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. DISCUSSION: The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).

Zirconium-89 labeled antibodies: a new tool for molecular imaging in cancer patients.

Antibody based positron emission tomography (immuno-PET) imaging is of increasing importance to visualize and characterize tumor lesions. Additionally, it can be used to identify patients who may benefit from a particular therapy and monitor the therapy outcome. In recent years the field is focused on (89)Zr, a radiometal with near ideal physical and chemical properties for immuno-PET. In this review we will discuss the production of (89)Zr, the bioconjugation strategies, and applications in (pre-)clinical studies of (89)Zr-based immuno-PET in oncology. To date, (89)Zr-based PET imaging has been investigated in a wide variety of cancer-related targets. Moreover, clinical studies have shown the feasibility for (89)Zr-based immuno-PET to predict and monitor treatment, which could be used to tailor treatment for the individual patient. Further research should be directed towards the development of standardized and robust conjugation methods and improved chelators to minimize the amount of released Zr(4+) from the antibodies. Additionally, further validation of the imaging method is required. The ongoing development of new (89)Zr-labeled antibodies directed against novel tumor targets is expected to expand applications of (89)Zr-labeled immuno-PET to a valuable method in the medical imaging.

[Pigtail stent for gallbladder drainage]. / 'Pigtail'-stent voor inwendige galblaasdrainage.

Endoscopic transpapillary gallbladder drainage is a new, relatively non-invasive treatment for patients with symptomatic gallbladder disease and a high surgery risk. Placement of an internal pigtail stent is an alternative treatment for percutaneous gallbladder drainage. This procedure can be performed in patients with a temporary contra-indication - in preparatory process to a cholecystectomy - as well as in patients with a prolonged contra-indication where the pigtail stent can remain in situ for a longer period of time. This technique appears to be an effective and safe procedure for patients with acute cholecystitis or symptomatic gallbladder disease and a high surgery risk.

Synthesis and initial preclinical evaluation of the P2X7 receptor antagonist [¹¹C]A-740003 as a novel tracer of neuroinflammation.

Neuroinflammation, in particular activation of microglia, is thought to play an important role in the progression of neurodegenerative diseases. In activated microglia, the purinergic P2X7 receptor is upregulated. A-740003, a highly affine and selective P2X7 receptor antagonist, is a promising candidate for the development of a radiotracer for imaging of neuroinflammation by positron emission tomography. For this purpose, [(11)C]A-740003 was synthesised and evaluated in vivo with respect to both tracer metabolism and biodistribution. In plasma, a moderate metabolic rate was seen. In healthy rat brain, only marginal uptake of [(11)C]A-740003 was observed and, therefore, metabolites in brain could not be determined. Whether the minimal brain uptake is due to the low expression levels of the P2X7 receptor in healthy brain or to limited transport across the blood-brain barrier has yet to be elucidated.