Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Surveillance for Presumed BD-IPMN of the Pancreas: Stability, Size, and Age Identify Targets for Discontinuation.

BACKGROUND & AIMS: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance. METHODS: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer. RESULTS: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5). CONCLUSIONS: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm.

Accurate prediction of histological grading of intraductal papillary mucinous neoplasia using deep learning.

BACKGROUND: Risk stratification and recommendation for surgery for intraductal papillary mucinous neoplasm (IPMN) are currently based on consensus guidelines. Risk stratification from presurgery histology is only potentially decisive owing to the low sensitivity of fine-needle aspiration. In this study, we developed and validated a deep learning-based method to distinguish between IPMN with low grade dysplasia and IPMN with high grade dysplasia/invasive carcinoma using endoscopic ultrasound (EUS) images. METHODS: For model training, we acquired a total of 3355 EUS images from 43 patients who underwent pancreatectomy from March 2015 to August 2021. All patients had histologically proven IPMN. We used transfer learning to fine-tune a convolutional neural network and to classify "low grade IPMN" from "high grade IPMN/invasive carcinoma." Our test set consisted of 1823 images from 27 patients, recruiting 11 patients retrospectively, 7 patients prospectively, and 9 patients externally. We compared our results with the prediction based on international consensus guidelines. RESULTS: Our approach could classify low grade from high grade/invasive carcinoma in the test set with an accuracy of 99.6 % (95 %CI 99.5 %-99.9 %). Our deep learning model achieved superior accuracy in prediction of the histological outcome compared with any individual guideline, which have accuracies between 51.8 % (95 %CI 31.9 %-71.3 %) and 70.4 % (95 %CI 49.8-86.2). CONCLUSION: This pilot study demonstrated that deep learning in IPMN-EUS images can predict the histological outcome with high accuracy.

Computed high-b-value high-resolution DWI improves solid lesion detection in IPMN of the pancreas.

OBJECTIVES: To examine the effect of high-b-value computed diffusion-weighted imaging (cDWI) on solid lesion detection and classification in pancreatic intraductal papillary mucinous neoplasm (IPMN), using endoscopic ultrasound (EUS) and histopathology as a standard of reference. METHODS: Eighty-two patients with known or suspected IPMN were retrospectively enrolled. Computed high-b-value images at b = 1000 s/mm2 were calculated from standard (b = 0, 50, 300, and 600 s/mm2) DWI images for conventional full field-of-view (fFOV, 3 × 3 × 4 mm3 voxel size) DWI. A subset of 39 patients received additional high-resolution reduced-field-of-view (rFOV, 2.5 × 2.5 × 3 mm3 voxel size) DWI. In this cohort, rFOV cDWI was compared against fFOV cDWI additionally. Two experienced radiologists evaluated (Likert scale 1-4) image quality (overall image quality, lesion detection and delineation, fluid suppression within the lesion). In addition, quantitative image parameters (apparent signal-to-noise ratio (aSNR), apparent contrast-to-noise ratio (aCNR), contrast ratio (CR)) were assessed. Diagnostic confidence regarding the presence/absence of diffusion-restricted solid nodules was assessed in an additional reader study. RESULTS: High-b-value cDWI at b = 1000 s/mm2 outperformed acquired DWI at b = 600 s/mm2 regarding lesion detection, fluid suppression, aCNR, CR, and lesion classification (p = < .001-.002). Comparing cDWI from fFOV and rFOV revealed higher image quality in high-resolution rFOV-DWI compared to conventional fFOV-DWI (p ≤ .001-.018). High-b-value cDWI images were rated non-inferior to directly acquired high-b-value DWI images (p = .095-.655). CONCLUSIONS: High-b-value cDWI may improve the detection and classification of solid lesions in IPMN. Combining high-resolution imaging and high-b-value cDWI may further increase diagnostic precision. CLINICAL RELEVANCE STATEMENT: This study shows the potential of computed high-resolution high-sensitivity diffusion-weighted magnetic resonance imaging for solid lesion detection in pancreatic intraductal papillary mucinous neoplasia (IPMN). The technique may enable early cancer detection in patients under surveillance. KEY POINTS: • Computed high-b-value diffusion-weighted imaging (cDWI) may improve the detection and classification of intraductal papillary mucinous neoplasms (IPMN) of the pancreas. • cDWI calculated from high-resolution imaging increases diagnostic precision compared to cDWI calculated from conventional-resolution imaging. • cDWI has the potential to strengthen the role of MRI for screening and surveillance of IPMN, particularly in view of the rising incidence of IPMNs combined with now more conservative therapeutic approaches.

Efficacy and Safety of Cold Snare Polypectomy of Colorectal Polyps 10-15 mm with a Hybrid Snare: A Prospective Observational Pilot Study.

INTRODUCTION: Cold snare polypectomy (CSP) is a safe and effective procedure for small colorectal polyps ≤9 mm. There are only limited data regarding CSP of larger neoplastic lesions. This study evaluated the efficacy and safety of CSP for polyps between 10 and 15 mm in size. METHODS: In this prospective single-arm observational pilot study, patients with a least one polyp 10-15 mm were included. These polyps were preferably removed by CSP using a dedicated hybrid snare. The primary outcome was the histological complete resection rate (CRR) determined by pathologically negative margins of the specimen and no neoplastic tissue obtained from biopsies of the resection site margin. Secondary outcomes were en bloc resection rate, failure of CSP, and incidence of adverse events. RESULTS: A total of 61 neoplastic polyps were removed from 39 patients. Overall CRR was 80.3% (49/61). CSP was feasible in 78.7% (48/61) of polyps and the CRR in this group was 85.4% (41/48). When CSP failed (13/61; 21.3%), lesions were successfully resected by immediate HSP using the same snare with a CRR of 61.5% (8/13) in this group. One patient presented delayed hemorrhage after HSP of a polyp but successful hemostasis was achieved with two hemoclips. No other adverse events occurred. No recurrence was seen on follow-up colonoscopy in cases with incomplete resected polyps. CONCLUSION: CSP seems to be efficient and safe in removing colorectal polyps up to 15 mm. A hybrid snare seems to be particularly advantageous for these polyps as it allows immediate conversion to HSP if CSP might fail in larger polyps. This trial is registered at ClinicalTrials.gov (NCT04464837).

Evaluation of a questionnaire to assess the indication for screening colonoscopy for asymptomatic patients.

INTRODUCTION: Colorectal cancer is the second most common cause of cancer death worldwide. Screening colonoscopy is a very effective measure to prevent colorectal cancer and can reduce mortality at the population level. However, the participation rates of screening programs are low.To provide easily accessible information on screening colonoscopy and to increase the participation rates of screening programs, we developed a questionnaire for asymptomatic patients based on the German guidelines to assess the indication for screening colonoscopy. We evaluated the questionnaire with reference to the indications given by specialists in gastroenterology. METHODS: Patients who visited a specialist in gastroenterology in an outpatient clinic of a tertiary hospital for other reasons than a colonoscopy were eligible for the study. A maximum of seven questions to assess the indication for screening colonoscopy were answered by the patients. Afterward, the indication for screening colonoscopy was given or not by a specialist in gastroenterology. The accuracy of the questionnaire was measured in terms of sensitivity, specificity, and predictive values. RESULTS: In total, 335 patients were included in the analyses, of whom 50 and 285 patients were given and were not given an indication for screening colonoscopy by the specialists, respectively. In 0/50 patients, the questionnaire was false negative and in 8/285 patients false positive. Thus, the questionnaire had a sensitivity of 100% (95% confidence interval: 93-100%), a specificity of 97% (95-99%), a negative predictive value of 100% (99-100%), and a positive predictive value of 86% (75-94%).A subgroup analysis including patients who had never had a colonoscopy (n=109) showed comparable results: sensitivity of 100% (92-100%), specificity of 92% (83-97%), negative predictive value of 100% (94-100%), and positive predictive value of 90% (87-97%). CONCLUSION: The self-assessment questionnaire for asymptomatic individuals to assess the recommendation for screening colonoscopy is very sensitive and specific compared to a specialist in gastroenterology.The questionnaire can be found at: https://www.interdisziplinaere-endoskopie.mri.tum.de/de/infos-patienten/index.php.

Prediction of Outcome in Acute Pancreatitis by the qSOFA and the New ERAP Score.

BACKGROUND: Early identification of patients with acute severe pancreatitis is important for prompt and adequate treatment. Existing scores for pancreatitis are often laborious or require serial patient evaluation, whereas the qSOFA score, that was established to predict outcome in patients with suspected infection, is simple to perform. AIMS AND METHODS: In this cohort study, we analyse the potential of the qSOFA score to predict outcome of patients with acute pancreatitis and refine the qSOFA score by rapid available laboratory parameters to the emergency room assessment of acute pancreatitis (ERAP) score. Validation was performed in a separate patient cohort. RESULTS: In total 203 patients with acute pancreatitis were recruited. The qSOFA score has the potential to predict ICU admission (AUC = 0.730, p = 0.002) and organ failure (AUC = 0.799, p = 0.013) in acute pancreatitis. Respiratory rate, mental status, blood urea nitrogen and C-reactive protein are the rapid available parameters with the highest individual impact in binary logistic regression analyses. Their combination to the ERAP score can predict severity of acute pancreatitis according to the revised Atlanta classification (AUC = 0.689 ± 0.041, p < 0.001), ICU admission (AUC = 0.789 ± 0.067, p < 0.001), multi-organ dysfunction syndrome (AUC = 0.963 ± 0.024, p < 0.001) and mortality (AUC = 0.952 ± 0.028, p = 0.001). The performance and prognostic validity for organ failure and mortality were validated in an independent patient cohort. CONCLUSION: The qSOFA is a rapidly available prognostic score in acute pancreatitis with limited prognostic validity. A combination with the laboratory parameters BUN and CRP results in the new ERAP score with outstanding prognostic validity for multi-organ dysfunction syndrome and mortality.

Integrated clinical case discussions - a fully student-organized peer-teaching program on internal medicine.

BACKGROUND: In response to students´ poor ratings of emergency remote lectures in internal medicine, a team of undergraduate medical students initiated a series of voluntary peer-moderated clinical case discussions. This study aims to describe the student-led effort to develop peer-moderated clinical case discussions focused on training cognitive clinical skill for first and second-year clinical students. METHODS: Following the Kern Cycle a didactic concept is conceived by matching cognitive learning theory to the competence levels of the German Medical Training Framework. A 50-item survey is developed based on previous evaluation tools and administered after each tutorial. Educational environment, cognitive congruence, and learning outcomes are assessed using pre-post-self-reports in a single-institution study. RESULTS: Over the course of two semesters 19 tutors conducted 48 tutorials. There were 794 attendances in total (273 in the first semester and 521 in the second). The response rate was 32%. The didactic concept proved successful in attaining all learning objectives. Students rated the educational environment, cognitive congruence, and tutorials overall as "very good" and significantly better than the corresponding lecture. Students reported a 70%-increase in positive feelings about being tutored by peers after the session. CONCLUSION: Peer-assisted learning can improve students´ subjective satisfaction levels and successfully foster clinical reasoning skills. This highlights successful student contributions to the development of curricula.

Comparison of cap-assisted endoscopy vs. side-viewing endoscopy for examination of the major duodenal papilla: a randomized, controlled, noninferiority crossover study.

BACKGROUND : Use of a side-viewing endoscope is currently mandatory to examine the major duodenal papilla; however, previous studies have used cap-assisted endoscopy for complete examination of the papilla. The aim of this study was to compare cap-assisted endoscopy with side-viewing endoscopy for examination of the major duodenal papilla. METHODS : This was a prospective, randomized, blinded, controlled, noninferiority crossover study. Patients were randomized to undergo either side-viewing endoscopy followed by cap-assisted endoscopy or cap-assisted endoscopy followed by side-viewing endoscope. Photographs of the major duodenal papilla were digitally edited to mask the cap area before they were evaluated by three blinded external examiners. Our primary end point was complete visualization of the major duodenal papilla. Secondary end points were the ability to examine the mucosal pattern, the overview of the periampullary region, overall satisfaction, and time to locate the papilla. RESULTS : 62 patients completed the study. Complete visualization of the major duodenal papilla was achieved in 60 examinations by side-viewing endoscopy and in 59 by cap-assisted endoscopy (97 % vs. 95 %). The difference between the two examinations was 1.6 % with a two-sided 95 % confidence interval of -4.0 % to 7.3 %, which did not exceed the noninferiority margin of 8 %. Cap-assisted endoscopy achieved better scores regarding the examination of mucosal pattern and overall satisfaction, whereas side-viewing endoscopy had a better overview score (P < 0.001, P = 0.004, and P < 0.001, respectively). There was no relevant difference in the median times to locate the major duodenal papilla. CONCLUSION : Cap-assisted endoscopy and side-viewing endoscopy had similar success rates for complete visualization of the major duodenal papilla. Cap-assisted endoscopy is superior to side-viewing endoscopy regarding the mucosal pattern and overall satisfaction. Side-viewing endoscopy gives a better overview of the periampullary region.

Increased risk of candidemia in patients with necrotising pancreatitis infected with candida species.

BACKGROUND AND OBJECTIVES: Candida infections are frequent in necrotising pancreatitis. Candidemia is associated with very high mortality and its risk due to infected pancreatic necrosis is unknown. So we aimed to assess potential risk factors and the risk of candidemia in necrotising pancreatitis. METHODS: We retrospectively searched our clinical database for the diagnosis necrotising pancreatitis from 2007 till March 2017 and entered relevant information in a database for statistical analysis. RESULTS: in total, 136 patients met the inclusion criteria. Candida infected pancreatic necrosis were found in 54 patients and 7 patients developed candidemia. Patients with Candida infected necrosis had a significantly higher in hospital mortality (35.2% versus 13.4%, p = 0.003). The highest mortality was observed in patients with candidemia (57.1% versus 20.2%, p = 0.042). Male gender (OR 0.32, CI 0.13-0.78, p = 0.013) and post-ERCP pancreatitis (OR 4.32, CI 1.01-18.36, p = 0.048) had a significant impact on the risk of Candida infections of pancreatic necrosis. Candidemia was significantly more frequent in patients with Candida infected necrosis (11.1% versus 1.2%, p = 0.016). Candida albicans was the most common species followed by Candida glabrata. CONCLUSION: Candidemia is a relevant complication of necrotising pancreatitis and associated with high mortality. If patients do not respond to antibiotic therapy empiric antifungal therapy should be discussed.

Cap Assisted Upper Endoscopy for Examination of the Major Duodenal Papilla: A Randomized, Blinded, Controlled Crossover Study (CAPPA Study).

OBJECTIVE: Examination of major duodenal papilla (MDP) by standard forward-viewing esophagogastroduodenoscopy (S-EGD) is limited. Cap assisted esophagogastroduodenoscopy (CA-EGD) utilizes a cap fitted to the tip of the endoscope that can depress the mucosal folds and thus might improve visualization of MDP. The aim of this study was to compare CA-EGD to S-EGD for complete examination of the MDP. METHODS: Prospective, randomized, blinded, controlled crossover study. Subjects scheduled for elective EGD were randomized to undergo S-EGD (group A) or CA-EGD (group B) before undergoing a second examination by the alternate method. Images of the MDP were evaluated by three blinded multicenter-experts. Our primary outcome measure was complete examination of the papilla. Secondary outcome measures were duration and overall diagnostic yield. RESULTS: A total of 101 patients were randomized and completed the study. Complete examination of MDP was achieved in 98 patients using CA-EGD compared to 24 patients using S-EGD (97 vs. 24%, P<0.001). Median duration from intubation of the esophagus until localization of the MDP was shorter with CA-EGD (46. vs. 96 s., P<0.001). In group A, 11 extra lesions and 12 additional incidental findings were detected by secondary CA-EGD, whereas neither were detected by secondary S-EGD in group B (22 vs. 0% and 24 vs. 0%, P<0.001 and P<0.001). CONCLUSION: CA-EGD enabled complete examination of MDP in almost all cases compared to a low success rate of S-EGD. CA-EGD detected a significant amount of lesions and incidental findings when added to S-EGD. CA-EGD is a safe and effective method for examination of MDP.

A systematic database-derived approach to improve indexation of transpulmonary thermodilution-derived global end-diastolic volume.

Global end-diastolic volume (GEDV) has been indexed to body surface area (BSA). However, data validating this indexation of GEDV are scarce. Furthermore, it has been suggested to index GEDV to "predicted BSA" based on predicted body weight. Therefore, we aimed to identify biometric parameters independently associated with GEDV. We analyzed a database including 3812 TPTD measurements in 234 patients treated in the ICU of a German university hospital. GEDVI indexed to actual BSA was significantly lower than GEDVI indexed to predicted BSA (748 ± 179 vs. 804 ± 190 mL/m2; p < 0.001). GEDV was independently associated with older age, male sex, height, and actual body weight. In a regression model for the estimation of GEDV, age and height were the most important parameters: Each year in age and each cm in height increased GEDV by 9 and 15 mL, respectively. In addition to height and weight also age and sex should be considered for indexation of GEDV.

Applicability of stroke volume variation in patients of a general intensive care unit: a longitudinal observational study.

Sinus rhythm (SR) and controlled mechanical ventilation (CV) are mandatory for the applicability of respiratory changes of the arterial curve such as stroke volume variation (SVV) to predict fluid-responsiveness. Furthermore, several secondary limitations including tidal volumes <8 mL/kg and SVV-values within the "gray zone" of 9-13% impair prediction of fluid-responsiveness by SVV. Therefore, we investigated the prevalence of these four conditions in general ICU-patients. This longitudinal observational study analyzed a prospectively maintained haemodynamic database including 4801 transpulmonary thermodilution and pulse contour analysis measurements of 278 patients (APACHE-II 21.0 ± 7.4). The main underlying diseases were cirrhosis (32%), sepsis (28%), and ARDS (17%). The prevalence of SR and CV was only 19.4% (54/278) in the first measurements (primary endpoint), 18.8% (902/4801) in all measurements and 26.5% (9/34) in measurements with MAP < 65 mmHg and CI < 2.5 L/min/m2 and vasopressor therapy. In 69.1% (192/278) of the first measurements and in 65.9% (3165/4801) of all measurements the patients had SR but did not have CV. In 1.8% (5/278) of the first measurements and in 2.5% (119/4801) of all measurements the patients had CV but lacked SR. In 9.7% (27/278) of the first measurements and in 12.8% (615/4801) of all measurements the patients did neither have SR nor CV. Only 20 of 278 (7.2%) of the first measurements and 8.2% of all measurements fulfilled both major criteria (CV, SR) and both minor criteria for the applicability of SVV. The applicability of SVV in ICU-patients is limited due to the absence of mandatory criteria during the majority of measurements.

Epidemiology, clinical presentation, diagnosis and treatment of autoimmune pancreatitis: A retrospective analysis of 53 patients.

BACKGROUND: Most of the data about epidemiology, clinical presentation and treatment of autoimmune pancreatitis (AIP) is based on case series or small study groups. We therefore analyzed all cases of AIP treated at our clinic retrospectively. METHODS: We searched our clinical database for the diagnosis pancreatitis between January 2007 and June 2014, selected patients with AIP and entered all relevant information in a database for statistical analysis. RESULTS: In total 53 patients with AIP were treated at our institution, 62% with type 1 and 23% with type 2 AIP. Gender distribution was male/female 3.1:1 for type 1 and 1:1.2 for type 2 AIP. The median age was 63.0 and 32.5 years for type 1 and type 2 AIP, respectively. The most common symptom is abdominal pain particular in patients with type 2 AIP whereas jaundice was only apparent in patients with type 1 AIP. The international diagnostic criteria seem to facilitate diagnosis of AIP as unnecessary pancreatic surgery in patients with AIP decreases. In 62.6% of the patients therapy was indicated and 84.8% showed a response to initial therapy with steroids. Recurring disease occurred in 28.3% of the cases but only 3.8% suffered a second relapse. Permanent maintenance therapy with steroids or additional therapy with immunomodulatory drugs is successful in recurring disease. CONCLUSION: Our data further corroborate previous findings on epidemiology, clinical presentation and treatment of AIP. AIP is a well manageable autoimmune disease in most patients. Better biopsy techniques and simplified diagnostic criteria might further alleviate diagnosis of AIP.

Is the size of the pancreas useful in diagnosing chronic pancreatitis? An ultrasound based, retrospective study.

BACKGROUND/OBJECTIVES: According to the widely accepted "Cambridge Classification", one of the morphological criteria for chronic pancreatitis (CP) is enlargement of the pancreas. Increased size seems to be an obvious feature of an inflammatory disease. However, it has never been validated so far, if CP is indeed accompanied by significant enlargement of the pancreas. METHODS: In this retrospective study, reference values for the size of the pancreas (head, body and tail measured in the transverse plane by transabdominal ultrasound) were established from 921 patients without pancreatic disease. Measurements were performed by a single investigator. Subsequently, the size of the pancreas from 72 patients with CP was compared to age- and sex-matched controls. RESULTS: Calculating the 5th and 95th percentile, reference values of the pancreatic size were as follows: head 1.5-3.1 cm (mean: 2.2); body 0.6-1.6 cm (mean: 1.1); tail 1.4-3.0 cm (mean: 2.1). The size of the pancreas correlated significantly with body height, weight and body mass index. Patients with CP had only a slightly but statistically significantly larger pancreas than controls. Mean values from the CP group were still between the 5th and 95th percentile of matched controls. CONCLUSIONS: Although the pancreas from patients with CP was statistically significantly larger compared to controls, the difference was only marginally. According to these data, it is at least questionable if pancreatic size is a helpful parameter for sonographic evaluation to discriminate chronic pancreatitis from healthy pancreas.

Influence of Sorafenib and Bevacizumab on pancreatic volume - A monocentric CT based analysis.

BACKGROUND/OBJECTIVES: Angiogenesis plays a central role in tumor growth and metastasis and tyrosine kinases are crucial in the modulation of growth factor signaling. Several side effects of tyrosine kinase inhibitors have been reported, including diarrhea due to pancreatic insufficiency. The suspected mechanism is the anti-angiogenetic effect of the inhibited vascular endothelial growth factor (VEGF) causing a disturbance of the microvasculation. The aim of the present study was to determine the volume of the pancreas before and after a therapy both with the multi-tyrosine kinase inhibitor Sorafenib and Bevacizumab, which is a humanized monoclonal immunoglobulin G1 antibody against VEGF. METHODS: Retrospective monocentric study including 42 patients who received either Sorafenib, Bevacizumab combined with Flourouracil and/or Irinotecan, or singly Flourouracil and Irinotecan for different non-pancreatic malignancies. The volume of the pancreas was measured before and after therapy by CT-scan based volumetry. RESULTS: The pancreatic volume was statistically significantly lower after treatment with Sorafenib (75.4 mL vs. 71.0 mL; p = 0.006) or Bevacizumab and Fluorouracil ± Irinotecan (71.8 mL vs. 62.6 mL; p = 0.020). The pancreatic volume did not change statistically significantly after treatment with Fluorouracil ± Irinotecan only (51.1 mL vs. 49.9 mL; p = 0.142). CONCLUSIONS: Pancreatic volume decreases statistically significantly under treatment with both the multi-tyrosine kinase inhibitor Sorafenib and the angiogenesis inhibitor Bevacizumab. This volume reduction is most likely due to a reduced microvasculation by inhibition of VEGF.

Volumetric gain of the human pancreas after left partial pancreatic resection: A CT-scan based retrospective study.

BACKGROUND/OBJECTIVES: Regeneration of the pancreas has been well characterized in animal models. However, there are conflicting data on the regenerative capacity of the human pancreas. The aim of the present study was to assess the regenerative capacity of the human pancreas. METHODS: In a retrospective study, data from patients undergoing left partial pancreatic resection at a single center were eligible for inclusion (n = 185). Volumetry was performed based on 5 mm CT-scans acquired through a 256-slice CT-scanner using a semi-automated software. RESULTS: Data from 24 patients (15 males/9 females) were included. Mean ± SD age was 68 ± 11 years (range, 40-85 years). Median time between surgery and the 1st postoperative CT was 9 days (range, 0-27 days; IQR, 7-13), 55 days (range, 21-141 days; IQR, 34-105) until the 2nd CT, and 191 days (range, 62-1902; IQR, 156-347) until the 3rd CT. The pancreatic volumes differed significantly between the first and the second postoperative CT scans (median volume 25.6 mL and 30.6 mL, respectively; p = 0.008) and had significantly increased further by the 3rd CT scan (median volume 37.9 mL; p = 0.001 for comparison with 1st CT scan and p = 0.003 for comparison with 2nd CT scan). CONCLUSIONS: The human pancreas shows a measurable and considerable potential of volumetric gain after partial resection. Multidetector-CT based semi-automated volume analysis is a feasible method for follow-up of the volume of the remaining pancreatic parenchyma after partial pancreatectomy. Effects on exocrine and endocrine pancreatic function have to be evaluated in a prospective manner.

Emergency video capsule endoscopy in patients with acute severe GI bleeding and negative upper endoscopy results.

BACKGROUND: In mid-GI bleeding, video capsule endoscopy (VCE) shows the best diagnostic yield for ongoing overt bleeding. To date, the utility of VCE in acute severe GI bleeding has been analyzed rarely. OBJECTIVE: To evaluate the impact of VCE when performed on patients with acute severe GI bleeding immediately after an initial negative upper endoscopy result. DESIGN: Prospective study. SETTING: Tertiary-care center. PATIENTS: Patients with melena, dark-red or maroon stool, hemodynamic instability, drop of hemoglobin level ≥2 g/dL/day, and/or need of transfusion ≥2 units of packed red blood cells per day were included. INTERVENTIONS: After a negative upper endoscopy result, emergency VCE was performed by immediate endoscopic placement of the video capsule into the duodenum. MAIN OUTCOME MEASUREMENTS: Rate of patients in whom emergency VCE correctly guided further diagnostic and therapeutic procedures. RESULTS: Upper endoscopy showed the source of bleeding in 68 of 88 patients (77%). In the remaining 20 patients (23%), emergency VCE was performed, which was feasible in 19 of 20 patients (95%; 95% confidence interval [CI], 75%-99%). Emergency VCE correctly guided further diagnostic and therapeutic procedures in 17 of 20 patients (85%; 95% CI, 62%-97%) and showed a diagnostic yield of 75% (95% CI, 51%-91%). LIMITATIONS: Single-center study, small sample size. CONCLUSION: In patients with acute severe GI bleeding and negative upper endoscopy results, emergency VCE can be useful for the immediate detection of the bleeding site and is able to guide further therapy. (Clinical trial registration number: NCT01584869.)

Predictors of the accuracy of pulse-contour cardiac index and suggestion of a calibration-index: a prospective evaluation and validation study.

BACKGROUND: Cardiac Index (CI) is a key-parameter of hemodynamic monitoring. Indicator-dilution is considered as gold standard and can be obtained by pulmonary arterial catheter or transpulmonary thermodilution (TPTD; CItd). Furthermore, CI can be estimated by Pulse-Contour-Analysis (PCA) using arterial wave-form analysis (CIpc). Obviously, adjustment of CIpc to CItd initially improves the accuracy of CIpc. Despite uncertainty after which time accuracy of CIpc might be inappropriate, recalibration by TPTD is suggested after a maximum of 8 h. We hypothesized that accuracy of CIpc might not only depend on time to last TPTD, but also on changes of the arterial wave curve detectable by PCA itself. Therefore, we tried to prospectively characterize predictors of accuracy and precision of CIpc (primary outcome). In addition to "time to last TPTD" we evaluated potential predictors detectable solely by pulse-contour-analysis. Finally, the study aimed to develop a pulse-contour-derived "calibration-index" suggesting recalibration and to validate these results in an independent collective. METHODS: In 28 intensive-care-patients with PiCCO-monitoring (Pulsion Medical-Systems, Germany) 56 datasets were recorded. CIpc-values at baseline and after intervals of 1 h, 2 h, 4 h, 6 h and 8 h were compared to CItd derived from immediately subsequent TPTD. Results from this evaluation-collective were validated in an independent validation-collective (49 patients, 67 datasets). RESULTS: Mean bias values CItd-CIpc after different intervals ranged between -0.248 and 0.112 L/min/m(2). Percentage-error after different intervals to last TPTD ranged between 18.6% (evaluation, 2 h-interval) and 40.3% (validation, 6 h-interval). In the merged data, percentage-error was below 30% after 1 h, 2 h, 4 h and 8 h, and exceeded 30% only after 6 h. "Time to last calibration" was neither associated to accuracy nor to precision of CIpc in any uni- or multivariate analysis. By contrast, the height of CIpc and particularly changes in CIpc compared to last thermodilution-derived CItd(base) univariately and independently predicted the bias CItd-CIpc in both collectives. Relative changes of CIpc compared to CItd(base) exceeding thresholds derived from the evaluation-collective (-11.6% < CIpc-CItd(base)/CItd(base) < 7.4%) were confirmed as significant predictors of a bias |CItd-CIpc| ≥ 20% in the validation-collective. CONCLUSION: Recalibration triggered by changes of CIpc compared to CItd(base) derived from last calibration should be preferred to fixed intervals.

Fungal "colonisation" is associated with increased mortality in medical intensive care unit patients with liver cirrhosis.

OBJECTIVES: Patients with liver cirrhosis are at increased risk for fungal infections. However, distinction of fungal colonisation (FC) and invasive mycoses is difficult. Aim of this study was to analyse the impact of FC on mortality of cirrhotic ICU-patients. METHODS: Retrospective mortality analysis of a prospectively maintained database on 120 cirrhotic patients with and without FC. Comparison to 120 noncirrhotic controls matched for APACHE-II (24.9 ± 3.7 vs. 25.0 ± 2.6; p = 0.263). RESULTS: About 69/120 (58%) of patients with cirrhosis had FC. These patients had significantly higher APACHE-II score and mortality compared to cirrhotic patients without FC (27 ± 3 vs. 23 ± 4, p < 0.001; 78 vs. 35%, p < 0.001). In multivariate analysis, FC was independently (p = 0.047) associated to mortality. Mortality of noncirrhotic patients with FC (14/31; 45.2%) was not different to noncirrhotic controls without FC [28/89 (31.2%; p = 0.168)]. Similarly, in multivariate analysis of noncirrhotics, APACHE-II (p < 0.001), but not FC, was independently associated to mortality. Multiple regression analysis of all 240 cirrhotic and noncirrhotic patients demonstrated that APACHE-II (p < 0.001), cirrhosis (p = 0.001) and FC (p = 0.049) were independently associated with mortality. CONCLUSION: Fungal "colonisation" is independently associated to mortality in cirrhotic ICU-patients. Early antimycotic therapy should be considered in critically ill cirrhotic patients with FC.