Sebastian Rasch

A clinical perspective on the role of chronic inflammation in gastrointestinal cancer.

Chronic inflammation has been identified as an important risk factor for the development of malignancy, and knowledge about its molecular and cellular mechanisms is increasing. Several chronic inflammatory diseases of the gastrointestinal tract are important as risk factors for malignancy and have been studied in detail. In this review, we summarize important molecular mechanisms in chronic inflammation and highlight established and potential links between chronic inflammation and gastrointestinal cancer. In addition, we present the role of chronic inflammation in numerous tumors within the gastrointestinal tract as well as the relevant pathways or epidemiologic observations linking the pathogenesis of these tumors to inflammation.

Comparison of 1,3-β-d-glucan with galactomannan in serum and bronchoalveolar fluid for the detection of Aspergillus species in immunosuppressed mechanical ventilated critically ill patients.

PURPOSE Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in immunocompromised critically ill patients. New diagnostic strategies for early detection of IPA include the noninvasive biomarkers 1,3-β-d-glucan (BDG), serum, and bronchoalveolar (BAL) fluid galactomannan (GM). The aim of this study was to compare these markers for early detection of IPA in immunosuppressed critically ill patients. METHODS Between December 2014 and December 2015, 49 immunosuppressed patients with respiratory failure were treated at our intensive care unit (ICU). We compared the BDG Fungitell assay with GM Platelia assay in serum and BAL for early detection of IPA. All tests were performed initially after admission at the ICU. RESULTS In our study with 49 patients, 13 (26%) had probable IPA. These patients had a higher Acute Physiology And Chronic Health Evaluation II score (28 vs 23, P<.001), Sequential Organ Failure Assessment score (16 vs 14, P<.001), more neutropenia (77% vs 30%, P<.001), worse Horowitz Index (99 vs 73 P<.020), a longer ICU stay (26 vs 17 days, P<.044), and a higher mortality rate (77% vs 58%, P<.001) as compared with patients without probable IPA. The used biomarker BDG presented in patients with probable IPA showed significantly higher levels as compared with patients without probable IPA (375 [103-1000 pg/mL; P<.001] vs 64 [30-105 pg/mL; P < .001]). Comparison of BDG with GM showed that positive serum GM could be detected in only 4 (30%), whereas positive BAL GM could be detected in 12 (92%; mean optical density index, 3.7) of 13 probable IPA cases. These results can be expressed as an overall sensitivity of 88% and a specificity of 82% for probable IPA using the BDG Fungitell assay, a sensitivity of 35% and a specificity of 70% using the serum GM Platelia assay, and a sensitivity of 70% and a specificity of 94% using the BAL GM Platelia assay. The negative predictive values of the used tests were 94% for the BDG Fungitell assay, 94% for the serum GM Platelia assay, and 90% for the BAL GM Platelia assay. CONCLUSION 1,3-β-d-Glucan may be a useful marker for patients under surveillance at risk for IPA. In critically ill patients with immunosuppression, early diagnosis of IPA may be improved by BDG as compared with serum GM. However, diagnostic performance and accuracy increase when BDG is run in parallel with GM from BAL; moreover, the association of the 2 parameters has also the advantage of detecting early and reliable IPA.

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.

Spontaneous Bleeding in Pancreatitis Treated by Transcatheter Arterial Coil Embolization: A Retrospective Study

Background/Objectives A rare, but life-threatening complication in pancreatitis is a spontaneous bleeding from intestinal vessels with or without previous formation of (pseudo-) aneurysms. And yet, the optimal diagnostic and therapeutic strategies remain unclear. Methods We performed a retrospective analysis of all patients with pancreatitis and intraabdominal bleeding at a German tertiary referral center between January 2002 and December 2012. Results Bleeding occurred in <1% (14/3,421) of patients with pancreatitis. Most involved vessels were arteria lienalis, arteria gastroduodenalis, and arteria pancreaticoduodenalis. All bleedings could be stopped by transcatheter arterial coil embolization. Recurrent bleeding after coil embolization occurred in 2/14 (14%) patients. Conclusions In cases of intraabdominal hemorrhage in patients with pancreatitis, transcatheter arterial coil embolization should be considered as the first interventional procedure.

Management of pancreatic pseudocysts-A retrospective analysis.

Background Pancreatic pseudocysts arise mostly in patients with alcohol induced chronic pancreatitis causing various symptoms and complications. However, data on the optimal management are rare. To address this problem, we analysed patients with pancreatic pseudocysts treated at our clinic retrospectively. Methods We searched our clinical database for the diagnosis pancreatitis from 2004 till 2014, selected patients with pseudocysts larger than 10 mm and entered all relevant information in a database for statistical analysis. Results In total, 129 patients with pancreatic pseudocysts were treated at our institution during the study period. Most patients suffered from alcohol induced chronic pancreatitis (43.4%; 56/129). Pseudocysts were more frequent in female than in male (2:1) and were mainly located in the pancreatic head (47.3%; 61/129). Local complications like obstructive jaundice were associated with the diameter of the cysts (AUC 0.697 in ROC-curve analysis). However, even cysts up to a diameter of 160 mm can regress spontaneously. Besides a lower re-intervention rate in surgically treated patients, endoscopic, percutaneous and surgical drainage are equally effective. Most treatment related complications occur in large pseudocysts located in the pancreatic head. Conclusion Conservative management of large pseudocysts is successful in many patients. Therefore, indication for treatment should be made carefully considering the presence and risk of local complications. Endoscopic and surgical drainage are equally effective.

[Autoimmune pancreatitis--treatment and pitfalls in diagnostics].

BACKGROUND Autoimmune pancreatitis (AIP) was first classified as a defined disease entity in 1995. It accounts for approximately 2 % of cases of chronic pancreatitis (western world prevalence 36-41/100,000 inhabitants) and AIP is diagnosed in 2.4 % of pancreas resection specimens. OBJECTIVES Presentation of strategies for diagnosis and treatment with focus on differentiation of AIP and pancreatic carcinoma. METHODS Selective literature research in PubMed regarding pathogenesis, diagnosis and treatment of AIP. RESULTS Key characteristics of AIP are recurrent jaundice due to obstructed bile ducts, histological evidence of fibrosis, a lymphoplasmocytic or granulocytic infiltrate and the response to steroid therapy. There are two distinctive forms of AIP: type I or lymphoplasmocytic sclerosing pancreatitis and type II or idiopathic duct centric pancreatitis. The IgG4 positive AIP type I belongs to the group of IgG4-related systemic diseases. Diagnosis of AIP is established according to the international consensus diagnostic criteria (ICDC) or HISORt (mnemonic standing for histology, imaging, serology, other organ involvement and response to therapy) criteria. Differentiation from pancreatic adenocarcinoma can be challenging. The standard treatment consists of corticosteroids and in some cases azathioprine can be added. In refractory disease rituximab is a further option. Treatment is indicated in patients with jaundice, systemic manifestation or persistent pain. CONCLUSION Although AIP is increasingly being identified, the differentiation from pancreatic adenocarcinoma still remains difficult and in cases of a suspicion of neoplasia, resection should be favored. It can successfully be treated conservatively with steroids and rituximab.

Autoimmune Pankreatitis – Behandlung und Problematik der Diagnosestellung

BACKGROUND Autoimmune pancreatitis (AIP) was first classified as a defined disease entity in 1995. It accounts for approximately 2 % of cases of chronic pancreatitis (western world prevalence 36-41/100,000 inhabitants) and AIP is diagnosed in 2.4 % of pancreas resection specimens. OBJECTIVES Presentation of strategies for diagnosis and treatment with focus on differentiation of AIP and pancreatic carcinoma. METHODS Selective literature research in PubMed regarding pathogenesis, diagnosis and treatment of AIP. RESULTS Key characteristics of AIP are recurrent jaundice due to obstructed bile ducts, histological evidence of fibrosis, a lymphoplasmocytic or granulocytic infiltrate and the response to steroid therapy. There are two distinctive forms of AIP: type I or lymphoplasmocytic sclerosing pancreatitis and type II or idiopathic duct centric pancreatitis. The IgG4 positive AIP type I belongs to the group of IgG4-related systemic diseases. Diagnosis of AIP is established according to the international consensus diagnostic criteria (ICDC) or HISORt (mnemonic standing for histology, imaging, serology, other organ involvement and response to therapy) criteria. Differentiation from pancreatic adenocarcinoma can be challenging. The standard treatment consists of corticosteroids and in some cases azathioprine can be added. In refractory disease rituximab is a further option. Treatment is indicated in patients with jaundice, systemic manifestation or persistent pain. CONCLUSION Although AIP is increasingly being identified, the differentiation from pancreatic adenocarcinoma still remains difficult and in cases of a suspicion of neoplasia, resection should be favored. It can successfully be treated conservatively with steroids and rituximab.

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.

Accuracy and precision of ScvO2 measured with the CeVOX-device: A prospective study in patients with a wide variation of ScvO2-values

Introduction Central-venous oxygen saturation (ScvO2) is a key parameter of hemodynamic monitoring and has been suggested as therapeutic goal for resuscitation. Several devices offer continuous monitoring features. The CeVOX-device (Pulsion Medical Systems) uses a fibre-optic probe inserted through a conventional central-venous catheter (CVC) to obtain continuous ScvO2. Objectives Since there is a lack of studies validating the CeVOX, we prospectively analyzed data from 24 patients with CeVOX-monitoring. To increase the yield of lower ScvO2-values, 12 patients were equipped with a femoral CVC. Methods During the 8h study period ScvO2_CeVOX was documented immediately before withdrawal of blood to measure ScvO2 by blood gas analysis (ScvO2_BGA) 6min, 1h, 4h, 5h and 8h after the initial calibration. No further calibrations were performed. Results In patients with jugular CVC (primary endpoint; 60 measurements), bias, lower and upper limits of agreement (LLOA; ULOA) and percentage error (PE) of the estimate of ScvO2 (ScvO2_CeVOX_jug) were acceptable with 0.45%, -13.0%, 13.9% and 16.6%, respectively. As supposed, ScvO2 was lower in the femoral compared to the jugular measurements (69.5±10.7 vs. 79.4±5.8%; p<0.001). While the bias (0.64%) was still acceptable, LLOA (-23.8%), ULOA (25.0%) and PE (34.5%) were substantially higher for femoral assessment of ScvO2 by the CeVOX (ScvO2_CeVOX_fem). Analysis of the entire data-pool with jugular as well as femoral CVCs allowed for a multivariate analysis which demonstrated that the position of the CVC per se was not independently associated with the bias ScvO2_CeVOX—ScvO2_BGA. The amount of the bias |ScvO2_CeVOX–ScvO2_BGA| was independently associated with the amount of the change of ScvO2_CeVOX compared to the initial calibration to ScvO2_BGA_baseline (|ScvO2_CeVOX—ScvO2_BGA_baseline|) as well as with low values of ScvO2_BGA_baseline. Furthermore, increasing time to the initial calibration was associated to the amount of the bias with borderline significance. A statistical model based on |ScvO2_CeVOX—ScvO2_BGA_baseline| and “time to last calibration” derived from an evaluation dataset (80 of 120 datasets, 16 of 24) provided a ROC-AUC of 0.903 to predict an amount of the bias |ScvO2_CeVOX–ScvO2_BGA| ≥5% in an independent validation group (40 datasets of 8 patients). Conclusion These findings suggest that the CeVOX device is capable to detect stability or instability of ScvO2_BGA. ScvO2_CeVOX accurately estimates ScvO2_BGA in case of stable values. However, intermittent measurement of ScvO2_BGA and re-calibration should be performed in case of substantial changes in ScvO2_CeVOX compared to baseline. Therefore, continuous measurement of ScvO2 with the CeVOX cannot replace ScvO2_BGA in instable patients. On the other hand, CeVOX might be useful for the monitoring of stable patients as a pre-test tool for more differentiated monitoring in case of changes in ScvO2_CeVOX.

Impact of large volume paracentesis on respiratory parameters including transpulmonary pressure and on transpulmonary thermodilution derived hemodynamics: A prospective study

Introduction Appropriate mechanical ventilation and prevention of alveolar collaps is mainly dependent on transpulmonary pressure TPP. TPP is assessed by measurement of esophageal pressure EP, largely influenced by pleural and intraabdominal pressure IAP. Consecutively, TPP-guided ventilation might be particularly useful in patients with high IAP. This study investigates the impact of large volume paracentesis LVP on TPP, EP, IAP as well as on hemodynamic and respiratory function in patients with liver cirrhosis and tense ascites. Material and methods We analysed 23 LVP-procedures in 11 cirrhotic patients ventilated with the AVEA Viasys respirator (CareFusion, USA) which is capable to measure EP via an esophageal tube. Results LVP of a mean volume of 4826±1276 mL of ascites resulted in marked increases in inspiratory (17.9±8.9 vs. 5.4±13.3 cmH2O; p<0.001) as well as expiratory TPP (-3.0±4.7 vs. -15.9±10.9 cmH2O; p<0.001; primary endpoint). In parallel, the inspiratory (2.4±8.7 vs. 14.1±14.5 cmH2O; p<0.001) and expiratory EP (12.4±6.0 vs. 24.9±11.3 cmH2O; p<0.001) significantly decreased. The effects were most pronounced for the release of the first 500 mL of ascites. LVP evoked substantial decreases in IAP and central venous pressure CVP. By contrast, mean arterial pressure, cardiac index, global end-diastolic volume index, extravascular lung water index and systemic vascular resistance index did not change. Among the respiratory parameters we observed an increase in paO2/FiO2 (247.7±60.9 vs. 208.3±46.8 mmHg; p<0.001) and a decrease in Oxygenation Index OI (4.8±2.0 vs. 5.8±3.1 cmH2O/mmHg; p = 0.002). Tidal volume (510±100 vs. 452±113 mL; p = 0.008) and dynamic respiratory system compliance Cdyn (46.8±15.9 vs. 35.1±14.6 mL/cmH20; p<0.001) increased, whereas paCO2 (47.3±10.7 vs. 51.2±12.3mmHg; p = 0.046) and the respiratory rate decreased (17.1±7.3 vs. 19.6±7.8 min-1; p = 0.010). Conclusions In mechanically ventilated patients with decompensated cirrhosis, intraabdominal hypertension resulted in a substantially decreased TPP despite PEEP-setting according to the ARDSNet. In these patients LVP markedly increased TPP and improved respiratory function in parallel with a decline of EP. Furthermore, LVP induced a decrease in IAP and CVP, while other hemodynamic parameters did not change.