Infection of (Peri-)Pancreatic Necrosis Is Associated with Increased Rates of Adverse Events during Endoscopic Drainage: A Retrospective Study.

Pancreatic necroses are a major challenge in the treatment of patients with pancreatitis, causing high morbidity. When indicated, these lesions are usually drained endoscopically using plastic or metal stents. However, data on factors associated with the occurrence of failure or adverse events during stent therapy are scarce. We retrospectively analyzed all adverse events and their associated features which occurred in patients who underwent a first-time endoscopic drainage of pancreatic necrosis from 2009 to 2019. During the observation period, a total of 89 eligible cases were identified. Adverse events occurred in 58.4% of the cases, of which 76.9% were minor (e.g., stent dislocation, residual lesions, or stent obstruction). However, these events triggered repeated interventions (63.5% vs. 0%, p < 0.001) and prolonged hospital stays (21.0 [11.8−63.0] vs. 14.0 [7.0−31.0], p = 0.003) compared to controls without any adverse event. Important factors associated with the occurrence of adverse events during endoscopic drainage therapy were positive necrosis cultures (6.1 [2.3−16.1], OR [95% CI], p < 0.001) and a larger diameter of the treated lesion (1.3 [1.1−1.5], p < 0.001). Superinfection of pancreatic necrosis is the most significant factor increasing the likelihood of adverse events during endoscopic drainage. Therefore, control of infection is crucial for successful drainage therapy, and future studies need to consider superinfection of pancreatic necrosis as a possible confounding factor when comparing different therapeutic modalities.

Over-the-scope-clips versus standard treatment in high-risk patients with acute non-variceal upper gastrointestinal bleeding: a randomised controlled trial (STING-2).

OBJECTIVE: Acute non-variceal upper gastrointestinal bleeding (NVUGIB) is managed by standard endoscopic combination therapy, but a few cases remain difficult and carry a high risk of persistent or recurrent bleeding. The aim of our study was to compare first-line over-the-scope-clips (OTSC) therapy with standard endoscopic treatment in these selected patients. DESIGN: We conducted a prospective, randomised, controlled, multicentre study (NCT03331224). Patients with endoscopic evidence of acute NVUGIB and high risk of rebleeding (defined as complete Rockall Score ≥7) were included. Primary endpoint was clinical success defined as successful endoscopic haemostasis without evidence of recurrent bleeding. RESULTS: 246 patients were screened and 100 patients were finally randomised (mean of 5 cases/centre and year; 70% male, 30% female, mean age 78 years; OTSC group n=48, standard group n=52). All but one case in the standard group were treated with conventional clips. Clinical success was 91.7% (n=44) in the OTSC group compared with 73.1% (n=38) in the ST group (p=0.019), with persistent bleeding occurring in 0 vs 6 in the OTSC versus standard group (p=0.027), all of the latter being successfully managed by rescue therapy with OTSC. Recurrent bleeding was observed in four patients (8.3%) in the OTSC group and in eight patients (15.4%) in the standard group (p=0.362). CONCLUSION: OTSC therapy appears to be superior to standard treatment with clips when used by trained physicians for selected cases of primary therapy of NVUGIB with high risk of rebleeding. Further studies are necessary with regards to patient selection to identify subgroups benefiting most from OTSC haemostasis. TRIAL REGISTRATION NUMBER: NCT03331224.

Metachronous carcinoma of the gastric tube following tumour-associated oesophagectomy.

INTRODUCTION: The prognosis of oesophageal carcinoma has improved during the last years. Thereby, the increasing survival has led to increasing occurrence of secondary gastric tube carcinoma (gastric conduit cancer, GTC) following oesophageal tumour resection. MATERIAL AND PATIENTS: A literature review (EMBASE, PubMed), spanning the years 2000 to 2020, identified 342 patients worldwide with a GTC following tumour-related oesophagectomy, of which 306 patients could be included for further analysis. RESULTS: The median age of 306 patients with GTC was 66.4 (39-80) years. 91.2% of patients (n = 279) were male. The median interval between oesophagectomy and GTC was 60.3 (4-236) months. 73.8% of patients (n = 226) were diagnosed as early cancer (EGC, T1) and 26.2% as advanced carcinoma (AGC, > T2; n = 80). Primary oesophagectomy was performed in 97.4% of patients (N = 298) for squamous cell carcinoma. AEG I carcinoma was present in only 5 patients (1.6%). In contrast, 99% (n = 303) of the GTC were found to be adenocarcinomas. One hundred eighty patients (58.8%) could be treated by endoscopic resection (ER). R0 resection was achieved in 82.8% (n = 149). The complication rate was 13.3% (n = 24) and the 30-day mortality 1.1% (n = 2) for ER. Eighty-three patients (27.1%) were treated surgically. These included 13 wedge resections, 25 partial resections and 45 total gastric graft resections with predominantly colon interposition. The R0 rate was 98.8% (n = 82). The postoperative morbidity was 24.1% (n = 20); the 90-day mortality was 6% (n = 5). In 43 patients (14%), palliative chemotherapy or radiotherapy or best supportive care took place. GTC diagnosed early in the EGC stage can be safely managed with ER. In cases of advanced GTC, surgical resection can be a potentially curative approach. Survival times of up to 120 months have been described after intervention for GTC.

Comparability of size measurements of the pancreas in magnetic resonance imaging and transabdominal ultrasound.

INTRODUCTION: Transabdominal ultrasound (US) and magnetic resonance imaging (MRI) are commonly used for the examination of the pancreas in clinical routine. We therefore were interested in the concordance of these two imaging methods for the size measurement of the pancreas and how age, gender, and body mass index (BMI) affect the organ size. METHODS: A total of 342 participants from the Study of Health in Pomerania underwent whole-body MRI and transabdominal US on the same day, and the diameter of the pancreatic head, body, and tail were measured. The agreement between US and MRI measurements was assessed by Bland and Altman plots. Intraclass correlation coefficients were used to compare observers. A multivariable regression model was applied using the independent variables age, gender, and body mass index. RESULTS: Compared to MRI, abdominal US returned smaller values for each segment of the pancreas, with a high level of inconsistency between these two methods. The mean difference was 0.39, 0.18, and 0.54 cm for the head, body, and tail, respectively. A high interobserver variability was detected for US. Multivariable analysis showed that pancreatic size in all three segments increased with BMI in both genders whereas pancreatic head and tail size decreased with age, an effect more marked in women. CONCLUSIONS: Agreement of pancreatic size measurements is poor between US and MRI. These limitations should be considered when evaluating morphologic features for pathologic conditions or setting limits of normal size. Adjustments for BMI, gender, and age may also be warranted.

Endoscopic management of complications of acute pancreatitis: an update on the field.

INTRODUCTION: Acute pancreatitis is a frequent, nonmalignant gastrointestinal disorder leading to hospital admission. For its severe form and subsequent complications, minimally invasive and endoscopic procedures are being used increasingly, and are subject to rapid technical advances. Areas covered: Based on a systematic literature search in PubMed, medline, and Web-of-Science, we discuss the currently available treatment strategies for endoscopic therapy of pancreatic pseudocysts, walled-off pancreatic necrosis (WON), and disconnected pancreatic duct syndrome (DPDS), and compare the efficacy and safety of plastic and metal stents. A special focus is placed on studies directly comparing different stent types, including lumen-apposing metal stents (LAMS) and clinical outcomes when draining pseudocysts or WONs. The clinical significance and endoscopic treatment options for DPDS are also discussed. Expert commentary: Endoscopic therapy has become the treatment of choice for different types of pancreatic and peripancreatic collections, the majority of which, however, require no intervention. The use of LAMS has facilitated drainage and necrosectomy in patients with WON or pseudocysts. Serious complications remain a problem in spite of high technical and clinical success rates. DPDS is an increasingly recognized problem in the presence of pseudocysts or WONs but evidence for endoscopic stent placement in this situation remains insufficient.

Effective treatment of benign biliary strictures with a removable, fully covered, self-expandable metal stent: A prospective, multicenter European study.

BACKGROUND: Temporary placement of removable, fully covered, self-expandable metal stents (fcSEMS) for treatment of benign biliary strictures (BBS) has been reported to be effective. However, the optimal extraction time point remains unclear and stent migration has been a major concern. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of this treatment modality using an fcSEMS with a special antimigration design and prolonged stent indwell time. METHODS: We performed a prospective, single-arm study at six tertiary care centers in Europe. Patients with BBS underwent endoscopic or percutaneous implantation of an fcSEMS (GORE® VIABIL® Biliary Endoprosthesis, W.L. Gore & Associates, Flagstaff, AZ, USA). The devices were scheduled to be removed nine months later, and patients were to return for follow-up for an additional 15 months. RESULTS: Forty-three patients were enrolled in the study. Stricture etiology was chronic pancreatitis in the majority of patients (57.5%). All fcSEMS were placed successfully, either endoscopically (76.7%) or percutaneously (23.3%). Stent migration was observed in two patients (5.2%). Primary patency of the SEMS prior to removal was 73.0%. All attempted stent removals were successful. At removal, stricture was resolved or significantly improved without need for further therapy in 78.9% of patients. Stricture recurrence during a follow-up of two years post-implant was observed in two patients. CONCLUSIONS: Temporary placement of the fcSEMS is a feasible, safe and effective treatment for BBS. The design of the device used in this study accounts for very low migration rates and facilitates easy stent retrieval, even after it has been in place for up to 11 months.

Gd-EOB-DTPA-enhanced MR guidance in thermal ablation of liver malignancies.

OBJECTIVE: To evaluate the potency of Gd-EOB-DTPA to support hepatic catheter placement in laser ablation procedures by quantifying time-dependent delineation effects for instrumentation and target tumor within liver parenchyma. Monitoring potential influence on online MR thermometry during the ablation procedure is a secondary aim. MATERIALS AND METHODS: 30 cases of MR-guided laser ablation were performed after i.v. bolus injection of gadoxetic acid (0.025 mmol/Kg Gd-EOB-DTPA; Bayer Healthcare, Berlin, Germany). T1-weighted GRE sequences were used for applicator guidance (FLASH 3D) in the catheter placement phase and for therapy monitoring (FLASH 2D) in the therapy phase. SNR and consecutive CNR values were measured for elements of interest plotted over time both for catheter placement and therapy phase and compared with a non-contrast control group of 19 earlier cases. Statistical analysis was realized using the paired Wilcoxon test. RESULTS: Sustainable signal elevation of liver parenchyma in the contrast-enhanced group was sufficient to silhouette both target tumor and applicator against the liver. Differences in time dependent CNR alteration were highly significant between contrast-enhanced and non-contrast interventions for parenchyma and target on the one hand (p = 0.020) and parenchyma and instrument on the other hand (p = 0.002). Effects lasted for the whole procedure (monitoring up to 60 min) and were specific for the contrast-enhanced group. Contrasting maxima were seen after median 30 (applicator) and 38 (tumor) minutes, in the potential core time of a multineedle procedure. Contrast influence on T1 thermometry for real-time monitoring of thermal impact was not significant (p = 0.068-0.715). CONCLUSION: Results strongly support anticipated promotive effects of Gd-EOB-DTPA for MR-guided percutaneous liver interventions by proving and quantifying the delineating effects for therapy-relevant elements in the procedure. Time benefit, cost effectiveness and oncologic outcome of the described beneficiary effects will have to be part of further investigations.

PRFS-based MR thermometry versus an alternative T1 magnitude method--comparative performance predicting thermally induced necrosis in hepatic tumor ablation.

OBJECTIVE: To compare the accuracy of a semi-quantitative proton resonance frequency shift (PRFS) thermal mapping interface and an alternative qualitative T1 thermometry model in predicting tissue necrosis in an established routine setting of MRI-guided laser ablation in the human liver. MATERIALS AND METHODS: 34 cases of PRFS-guided (GRE) laser ablation were retrospectively matched with 34 cases from an earlier patient population of 73 individuals being monitored through T1 magnitude image evaluation (FLASH 2D). The model-specific real-time estimation of necrotizing thermal impact (above 54 °C zone and T1 signal loss, respectively) was correlated in size with the resulting necrosis as shown by lack of enhancement on the first-day contrast exam (T1). Matched groups were compared using the Mann-Whitney test. RESULTS: Online PRFS guidance was available in 33 of 34 cases. Positive size correlation between calculated impact zone and contrast defect at first day was evident in both groups (p < 0.0004). The predictive error estimating necrosis was median 21% (range 1 %-52%) in the PRFS group and 61 % (range 22-84%) in the T1 magnitude group. Differences in estimating lethal impact were significant (p = 0.004), whereas the real extent of therapy-induced necrosis showed no significant difference (p > 0.28) between the two groups. CONCLUSION: PRFS thermometry is feasible in a clinical setting of thermal hepatic tumor ablation. As an interference-free MR-tool for online therapy monitoring its accuracy to predict tissue necrosis is superior to a competing model of thermally induced alteration of the T1 magnitude signal.

Pre-study protocol MagPEP: a multicentre randomized controlled trial of magnesium sulphate in the prevention of post-ERCP pancreatitis.

BACKGROUND: Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In spite of continuing research, no pharmacologic agent capable of effectively reducing the incidence of ERCP-induced pancreatitis has found its way into clinical practise. A number of experimental studies suggest that intrapancreatic calcium concentrations play an important role in the initiation of intracellular protease activation, an initiating step in the course of acute pancreatitis. Magnesium can act as a calcium-antagonist and counteracts effects in calcium signalling. It can thereby attenuate the intracellular activation of proteolytic digestive enzymes in the pancreas and reduces the severity of experimental pancreatitis when administered either intravenously or as a food supplement. METHODS: We designed a randomized, double-blind, placebo-controlled phase III study to test whether the administration of intravenous magnesium sulphate before and after ERCP reduces the incidence and the severity of post-ERCP pancreatitis. A total of 502 adult patients with a medical indication for ERCP are to be randomized to receive either 4930 mg magnesium sulphate (= 20 mmol magnesium) or placebo 60 min before and 6 hours after ERCP. The incidence of clinical post-ERCP pancreatitis, hyperlipasemia, pain levels, use of analgetics and length of hospital stay will be evaluated. CONCLUSIONS: If magnesium sulphate is found to be effective in preventing post-ERCP pancreatitis, this inexpensive agent with limited adverse effects could be used as a routine pharmacological prophylaxis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46556454.

Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey.

OBJECTIVE: The objective of this study was to clarify the clinical and pathophysiological characteristics of autoimmune pancreatitis (AIP) and its subtypes (lymphoplasmacytic sclerosing pancreatitis [LPSP] and idiopathic duct-centric pancreatitis [IDCP]) seen around the world. METHODS: An international multicenter survey of AIP was conducted in 15 institutes from 8 countries. We compared clinical and pathologic profiles of AIP (n = 731) and the clinical profiles of LPSP (n = 204) and IDCP (n = 64) patients. RESULTS: Patients with LPSP were approximately 16 years older than IDCP patients. Obstructive jaundice was a more frequent presentation in LPSP versus IDCP (75% vs 47%, P < 0.001), whereas abdominal pain (41% vs 68%, P < 0.001) and acute pancreatitis (5% vs 34%, P < 0.001) were more frequent in IDCP patients. Patients with LPSP were more likely to have diffuse swelling of the pancreas (40% vs 25%, P = 0.037) and elevated serum IgG4 levels (63% vs 23%, P < 0.001) but less likely to be associated with ulcerative colitis (1% vs 16%, P < 0.001). Clinical profiles of non-histologically confirmed AIP from Asia, the United States, and United Kingdom corresponded with that of LPSP, whereas those from Italy and Germany suggested a mixture of LPSP and IDCP. CONCLUSIONS: Autoimmune pancreatitis is seen all around the world, with regional differences in the pathologic and clinical features. Lymphoplasmacytic sclerosing pancreatitis and IDCP have distinct clinical profiles.

[Chronic pancreatitis as a risk factor for the development of pancreatic cancer--diagnostic challenges]. / Chronische Pankreatitis als Risikofaktor für ein Pankreaskarzinom--diagnostische Herausforderungen.

Patients with chronic pancreatitis are burdened with an increased risk of developing pancreatic cancer. Strategies or guidelines for the surveillance and early detection of pancreatic adenocarcinoma in patients with chronic pancreatitis are not established, because available clinical, serologic or imaging techniques are still of limited sensitivity and specificity. Despite these limitations do patients with chronic pancreatitis and suspected pancreatic cancer need a careful and sometimes repeated diagnostic work-up. A clear benefit of surveillance programs outside of clinical trials for the early detection of pancreatic cancer has not been demonstrated. A 51-year-old patient with chronic pancreatitis is reported who developed cancer of the pancreatic head while undergoing repeated imaging studies.

Autoimmune pancreatitis.

Autoimmune pancreatitis is a rare systemic fibrotic inflammatory disorder that can affect organs such as the bile ducts, salivary glands, and retroperitoneal lymph nodes, in addition to the pancreas. Morphological characteristics of autoimmune pancreatitis include a diffusely enlarged 'sausage-shaped' pancreas and an irregularly narrowed duct of Wirsung. According to the revised Japan Pancreas Society criteria, the diagnosis of autoimmune pancreatitis requires that one or more secondary serologic or histologic criteria are also met: the presence of autoantibodies, elevated levels of gamma-globulins, IgG or IgG(4), a lymphoplasmacytic infiltrate, or pancreatic fibrosis. The presence in any affected organ of a lymphoplasmacytic inflammatory infiltrate containing greater than 10 IgG(4)-positive cells per high-power field is pathognomonic for autoimmune pancreatitis. Precise data on the incidence and prevalence of autoimmune pancreatitis are currently not available because most reports involve either limited patient series or resection specimen cohorts. New diagnostic tools and further studies of the underlying pathophysiology and prognosis of autoimmune pancreatitis are needed for adequate and effective treatment strategies to be developed. The most crucial issue when caring for patients with suspected autoimmune pancreatitis is to differentiate autoimmune pancreatitis from pancreatic carcinoma, because pancreatic carcinoma requires surgery, whereas autoimmune pancreatitis responds well to steroid treatment.

Overlap syndrome of autoimmune pancreatitis and cholangitis associated with secondary Sjögren's syndrome.

In approximately 25% of patients with acute or chronic pancreatitis the cause remains unclear. Despite progress in understanding so-called idiopathic pancreatitis, more diagnostic criteria are needed. We report on a patient who presented with jaundice, but without pain or fever. Under the assumption of pancreatic cancer the patient underwent hemipancreatoduodenectomy. Histological examination showed chronic sclerosing inflammation of the pancreas and bile ducts without any signs of malignancy. Ten weeks later he developed bilateral parotid swelling and recurrent bouts of fever. Again liver enzymes were elevated and unsuccessfully treated with antibiotics for bacterial cholangitis. Further biopsies from submandibular gland, lymph nodes and liver again showed chronic sclerosing inflammation with lymphoplasmacytic infiltration. For sicca symptoms the diagnosis of a primary Sjogren's syndrome was proposed. However, with corticosteroid treatment the patient improved remarkably but after tapering he relapsed. On the basis of established criteria, we diagnosed autoimmune pancreatitis with (1) diffuse swelling of the pancreas, (2) irregularities of the pancreatic duct, (3) lymphoplasmacytic infiltration, (4) response to corticosteroids, (5) hypergammaglobulinaemia, and (6) disproportionately raised IgG4. In addition, the patient fulfilled the criteria for secondary Sjogren's syndrome. Autoimmune pancreatitis may present as an isolated or syndromic disease. It is an autoimmune disorder of unknown cause and should be included in the differential diagnosis of pancreatic disorders.

Clinical relevance of CD95 (Fas/Apo-1) on T cells of patients with B-cell chronic lymphocytic leukemia.

OBJECTIVE: Apoptosis mediated via CD95 (Fas/Apo-1) is a key regulator for the biology of normal and malignant lymphocytes. Although the function of CD95 on B-cell chronic lymphocytic leukemia cells (B-CLL cells) has been studied intensively, the clinical importance of CD95 expression on normal T cells in B-CLL has not been clarified. This study aimed to investigate whether expression of CD95 on peripheral blood T cells correlates with clinically relevant parameters of B-CLL disease. MATERIALS AND METHODS: Expression of CD95 (Fas/Apo-1) on peripheral blood T lymphocytes of patients with B-CLL was determined using flow cytometry and was correlated with expression of activation markers, sensitivity to apoptosis by anti-CD95, and clinical data, such as blood count, Binet stage, therapy, progression-free probability, and survival probability. RESULTS: Differential CD95 expression did not correlate with activation markers or with levels of apoptosis through anti-CD95. However, high levels of CD95 on T cells from B-CLL patients correlated significantly with low lymphocyte doubling time, increased Binet stages, and requirement for chemotherapeutic treatment. Furthermore, increased cell-surface CD95 on T cells was associated with reduced progression-free probability and poorer survival. CONCLUSIONS: CD95 levels on T cells correlate with the clinical course of B-CLL. Prospective studies appear warranted to investigate whether CD95 on T cells has a direct influence on B-CLL disease progression.