Severity of gallstone, sludge or microlithiasis induced pancreatitis - all of the same?

BACKGROUND/AIM: Severity of microlithiasis and sludge-induced pancreatitis in comparison to gallstone-induced pancreatitis has never been studied for a lack of definition. In order to understand whether bile duct obstruction or other mechanisms contribute to biliary pancreatitis severity we performed a monocentric, retrospective cohort study. METHODS: In this retrospective cohort study 263 patients with acute biliary pancreatitis treated at a tertiary care center from 2005 to 2021 were stratified according to the recent consensus definition for microlithiasis and sludge. The gallstone-pancreatitis cohort was compared to microlithiasis, sludge and suspected stone passage pancreatitis cohorts in terms of pancreatitis outcome, liver function and EUS/ERCP results using one-way ANOVA and Chi2 test. Multinomial logistic regression analysis was performed to correct for bias. RESULTS: Microlithiasis and sludge-induced pancreatitis classified according to the revised Atlanta classification, did not present with a milder course than gallstone-induced pancreatitis (p = 0.62). Microlithiasis and sludge showed an increase in bilirubin on the day of admission to hospital, which was not significantly different from gallstone-induced pancreatitis (p = 0.36). The likelihood of detecting biliary disease on EUS resulting in bile duct clearance was highest on the day of admission and day 1, respectively. CONCLUSION: Microlithiasis and sludge induce gallstone-equivalent impaired liver function tests and induce pancreatitis with similar severity compared with gallstone-induced acute biliary pancreatitis.

Stereotactic body radiotherapy for pancreatic cancer - A systematic review of prospective data.

Purpose: This systematic review aims to comprehensively summarize the current prospective evidence regarding Stereotactic Body Radiotherapy (SBRT) in various clinical contexts for pancreatic cancer including its use as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC), induction therapy for locally advanced pancreatic cancer (LAPC), salvage therapy for isolated local recurrence (ILR), adjuvant therapy after radical resection, and as a palliative treatment. Special attention is given to the application of magnetic resonance-guided radiotherapy (MRgRT). Methods: Following PRISMA guidelines, a systematic review of the Medline database via PubMed was conducted focusing on prospective studies published within the past decade. Data were extracted concerning study characteristics, outcome measures, toxicity profiles, SBRT dosage and fractionation regimens, as well as additional systemic therapies. Results and conclusion: 31 studies with in total 1,571 patients were included in this review encompassing 14 studies for LAPC, 9 for neoadjuvant treatment, 2 for adjuvant treatment, 2 for ILR, with an additional 4 studies evaluating MRgRT. In LAPC, SBRT demonstrates encouraging results, characterized by favorable local control rates. Several studies even report conversion to resectable disease with substantial resection rates reaching 39%. The adoption of MRgRT may provide a solution to the challenge to deliver ablative doses while minimizing severe toxicities. In BRPC, select prospective studies combining preoperative ablative-dose SBRT with modern induction systemic therapies have achieved remarkable resection rates of up to 80%. MRgRT also holds potential in this context. Adjuvant SBRT does not appear to confer relevant advantages over chemotherapy. While prospective data for SBRT in ILR and for palliative pain relief are limited, they corroborate positive findings from retrospective studies.

[Pancreatic cancer-screening or surveillance?] / Pankreaskarzinom ­ Screening oder Surveillance?

BACKGROUND: Despite continuous improvement of diagnostic and therapeutic procedures, the number of new pancreatic ductal adenocarcinoma (PDAC) cases diagnosed annually almost equals the number of PDAC-related deaths. Prerequisite for curative treatment is a resectable tumor at the time of diagnosis. Individuals with genetic and/or familial risk profiles should therefore be screened and included in structured surveillance programs. OBJECTIVES: Description of the status quo and usefulness of current PDAC screening and surveillance concepts. METHODS: A selective literature search of current national and international guidelines including underlying literature was performed. RESULTS: Nearly half of pancreatic cancer cases are missed by currently available surveillance programs, even in high-risk cohorts. Magnetic resonance imaging and endoscopic ultrasound supplemented by CA19­9 (± HbA1c) are not accurate enough to ensure robust earlier pancreatic cancer detection. Complementary biomarker panels will take on a crucial diagnostic role in the future.

[Cystic pancreatic lesions-indications, timing and reasons for surveillance]. / Pankreaszysten ­ Indikationen, Zeitpunkt und Rationale für eine Surveillance.

BACKGROUND: Cystic pancreatic lesions are detected incidentally at an increasing rate. Often, the patients present asymptomatically. Hence, the resulting clinical consequences remain challenging and unsettling for both physicians and patients. OBJECTIVES: Status of current recommendations in handling cystic pancreatic lesions. MATERIALS AND METHODS: Selective literature search of PubMed while taking current guidelines into account. RESULTS: Correct diagnostic classification of the cystic lesion is crucial since further action depends on the type of cystic lesion. Resection is generally recommended for mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN), and intraductal papillary mucinous neoplasms (IPMN) with relevant risk criteria such as prominent main-duct dilation. Surveillance is recommended for IPMN without risk criteria, as long as comorbidities and life expectancy of the patient will allow preventive resection over the years. SCNs are benign and only symptomatic SCNs require resection. Inflammatory pancreatic cysts should only be treated under certain circumstances.

The additive value of CA19.9 monitoring in a pancreatic cyst surveillance program.

BACKGROUND: Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population. METHODS: The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months. RESULTS: Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p < 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1-13, p = 0.03). CONCLUSIONS: In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.

Independent Validation and Assay Standardization of Improved Metabolic Biomarker Signature to Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature. METHODS: We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance. RESULTS: The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-9 >2 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-9 <37 U/mL, 39.7%, 94.1%, and 76.3%, respectively. CONCLUSIONS: The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.

Follow-up lung ultrasound to monitor lung failure in COVID-19 ICU patients.

OBJECTIVES: Point-of-care lung ultrasound (LU) is an established tool in the first assessment of patients with coronavirus disease (COVID-19). To assess the progression or regression of respiratory failure in critically ill patients with COVID-19 on Intensive Care Unit (ICU) by using LU. MATERIALS AND METHODS: We analyzed all patients admitted to Internal Intensive Care Unit, Ludwig-Maximilians-University (LMU) of Munich, from March 2020 to December 2020 suffering lung failure caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). LU was performed according to a standardized protocol at baseline and at follow up every other day for the first 15 days using a lung ultrasound score (LUSS). Ventilation data were collected simultaneously. RESULTS: Our study included 42 patients. At admission to ICU, 19 of them (45%) were mechanically ventilated. Of the non-invasive ventilated ones (n = 23, 55%), eleven patients required invasive ventilation over the course. While LUS did not differ at admission to ICU between the invasive ventilated ones (at baseline or during ICU stay) compared to the non-invasive ventilated ones (12±4 vs 11±2 points, p = 0.2497), LUS was significantly lower at d7 for those, who had no need for invasive ventilation over the course (13±5 vs 7±4 points, p = 0.0046). Median time of invasive ventilation counted 18 days; the 90-day mortality was 24% (n = 10) in our cohort. In case of increasing LUS between day 1 (d1) and day 7 (d7), 92% (n = 12/13) required invasive ventilation, while it was 57% (n = 10/17) in case of decreasing LUS. At d7 we found significant correlation between LU and FiO2 (Pearson 0.591; p = 0.033), p/F ratio (Pearson -0.723; p = 0.005), PEEP (Pearson 0.495; p = 0.043), pplat (Pearson 0.617; p = 0.008) and compliance (Pearson -0.572; p = 0.016). CONCLUSION: LUS can be a useful tool in monitoring of progression and regression of respiratory failure and in indicating intubation in patients with COVID-19 in the ICU.

Role of stereotactic body radiation in the enhancement of the quality of life in locally advanced pancreatic adenocarcinoma: a systematic review.

INTRODUCTION: Up to 30% of pancreatic cancer patients initially present locally advanced (LAPC). Stereotactic body radiation therapy (SBRT) may be an additional palliative treatment option when curative resection is no longer achievable. Our systematic review aimed to assess the effect of SBRT on the quality of life in LAPC. METHODS: We searched five databases until June 29th, 2021, for original articles that reported on SBRT for histologically proven LAPC in adults. Data were extracted on study characteristics, SBRT and additional therapy regimen, pain, biliary complications, nutrition, quality of life and other patient-reported outcomes. Statistical analyses were performed for population and survival data. RESULTS: 11 case series studies comprising 292 patients with a median age of 66 (range 34-89) years were included in the final analysis. The weighted average BED2;10 (radiation biologically effective dose, equivalent dose in 2 Gy fractions) was 54 Gy, delivered in 3 to 6 fractions. The individual studies used different scales and endpoints, not allowing a meta-analysis. Pain generally appeared to be improved by SBRT. SBRT significantly reduced jaundice. Local control was achieved in 71.7% of patients. Weight loss and nausea also tended to improve after SBRT. CONCLUSION: SBRT of locally advanced irresectable pancreatic cancer is a promising approach for achieving local control and improving the quality of life. However, randomized controlled trials with larger cohorts are needed to assess the value of SBRT in pancreatic cancer therapy.