Point-shear wave elastography generated by acoustic radiation force impulse in chronic pancreatitis.

BACKGROUND: Transcutaneous point-shear wave elastography (p-SWE) performed using an acoustic radiation force impulse can be used to quantify pancreatic stiffness in chronic pancreatitis (CP). We aimed to evaluate its usefulness to diagnose and monitor CP. METHODS: 175 participants were included in this prospective study including patients with CP (n = 65), liver cirrhosis (LC; n = 60), alcohol abuse (n = 10) and healthy controls (n = 40). Point-shear wave elastography of the pancreas was performed and quantified as median shear wave velocity (SWV). In the same way, p-SWE of the spleen served as a marker of portal hypertension. The M-ANNHEIM Severity score was used as global marker for disease activity in CP. RESULTS: Compared to healthy controls, pancreatic SWV was significantly elevated in CP (1.38 vs. 0.96 m/s; p < 0.0001, MWU-test). Pancreatic SWV was increased in alcoholic CP but not in hereditary CP. Receiver operating characteristic analysis revealed 1.2 m/s as the optimal cut-off to identify non-heredity-CP subjects (90% specificity; 81% sensitivity; 92% positive predictive value). Pancreatic SWV correlated significantly with the M-ANNHEIM Severity score, severity of CP-typical complications (both p < 0.05, linear regression analysis), morphological changes of the pancreas and need for hospital treatment (both p < 0.05, MWU-test) but not with exocrine or endocrine insufficiency. Pancreatic SWV >1.7 m/s was identified to predict M-ANNHEIM Severity score ≥11 points. Pancreatic SWV was also elevated in LC (1.42 m/s; p < 0.001), correlating with increased splenic SWV. CONCLUSION: Transcutaneous pancreatic p-SWE represents a bedside, cost-effective and non-invasive tool which adds valuable information to the process of diagnosing and monitoring CP. By portal hypertension, an increased pancreatic SWV must be expected.

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Impact of alcohol and smoking cessation on the course of chronic pancreatitis.

OBJECTIVES: Alcohol and nicotine are the two most important risk factors of chronic pancreatitis and they often occur together. It is still unclear how much they influence the severity of the disease and which of the two addictions should be treated with priority. METHODS: We performed a single-center, retrospective, cross-sectional study in a mixed medicosurgical cohort of 870 patients diagnosed with chronic pancreatitis (CP). We analyzed the impact of the drinking pattern and abstinence for alcohol and nicotine on the course of the disease. Patients with alcoholic CP were subdivided in I) patients with "life-time drinking history" (LTDH), II) "current drinkers" with current alcohol abuse without signs of LTDH, and III) "former drinkers" who stopped or reduced alcohol intake dramatically. RESULTS: Compared to patients with LTDH, "former drinkers" had a lower rate of exocrine insufficiency (29% vs. 59%) and pseudocysts (33% vs. 49%), were more often relapse-free (37% vs. 5%) and had less abdominal pain. There was no correlation detected between the quantity of alcohol consumption and the severity or progression of the disease. Regarding nicotine, 29 pack years are the threshold for developing early stage of CP. Under nicotine abstinence, only slightly more patients were relapse-free (37% vs. 22%). In contrast, the cumulative amount of nicotine consumed correlated with overall disease severity and the development of pseudocysts. The need for surgery was increased with odds ratios of 1.8 for both, alcohol and nicotine abuse. CONCLUSIONS: Alcohol cessation in chronic pancreatitis reduces exocrine insufficiency, abdominal pain and local complications. The effect of nicotine cessation is less pronounced in our cohort. However, nicotine abuse represents an important factor for the development of the disease.

Targeting the Cancer-Neuronal Crosstalk in the Pancreatic Cancer Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive solid tumors with a dismal prognosis and an increasing incidence. At the time of diagnosis, more than 85% of patients are in an unresectable stage. For these patients, chemotherapy can prolong survival by only a few months. Unfortunately, in recent decades, no groundbreaking therapies have emerged for PDAC, thus raising the question of how to identify novel therapeutic druggable targets to improve prognosis. Recently, the tumor microenvironment and especially its neural component has gained increasing interest in the pancreatic cancer field. A histological hallmark of PDAC is perineural invasion (PNI), whereby cancer cells invade surrounding nerves, providing an alternative route for metastatic spread. The extent of PNI has been positively correlated with early tumor recurrence and reduced overall survival. Multiple studies have shown that mechanisms involved in PNI are also involved in tumor spread and pain generation. Targeting these pathways has shown promising results in alleviating pain and reducing PNI in preclinical models. In this review, we will describe the mechanisms and future treatment strategies to target this mutually trophic interaction between cancer cells to open novel avenues for the treatment of patients diagnosed with PDAC.

Endoscopic Submucosal Dissection of a Giant Rectal Adenoma Manifesting as McKittrick-Wheelock Syndrome.

McKittrick-Wheelock syndrome (MKWS) is an uncommon clinical manifestation of large, villous, epithelial lesions of the distal colon and rectum. Excessive secretion of electrolyte-rich mucus from these lesions leads to secretory diarrhea, electrolyte disorders and acute renal failure. Several cases of MKWS have been reported since its initial description in 1954. The definitive treatment for the great majority of MKWS cases has consisted of surgical resection of the affected part of the colorectum, usually in the form of a low anterior resection or an abdominoperineal resection with the formation of an ostomy. Recent developments in endoscopic resection techniques now offer new, minimally invasive treatment alternatives for MKWS patients. We present the first reported case in the Western world of MKWS caused by a rectal adenoma with a size of 19 × 10 cm, treated through endoscopic submucosal dissection. Through the lessons learned by this case, as well as by a thorough review of the literature, we discuss this uncommon syndrome, focusing on treatment alternatives.

Impact of etiology on disease course in chronic pancreatitis.

BACKGROUND: Complications in chronic pancreatitis (CP) can be grouped in inflammatory (ICC) and fibrotic (FCC) clusters and pancreatic insufficiency cluster (PIC). However, the association between etiological risk factors and the development of complication clusters remains obscure. In this study, the impact of the etiology and disease duration on disease onset and development of complications was investigated. METHODS: This cross-sectional study recruited patients with CP from Mannheim/Germany (n = 870), Gießen/Germany (n = 100) und Donetsk/Ukraine (n = 104). Etiological risk factors, disease stage, age at disease onset, complications, need for hospitalization and surgery were noted. RESULTS: In 1074 patients diagnosed with CP, main risk factors were alcohol and nicotine abuse. An earlier onset of the disease was observed upon nicotine abuse (-4.0 years). Alcohol abuse was only associated with an earlier onset of the definite stage of CP. Alcohol abuse was the major risk factor for the development of ICC (p < 0.0001, multiple regression modeling). Abstinence of alcohol reduced ICC, whereas abstinence of nicotine showed no association. PIC correlated with efferent duct abnormalities and the disease duration. In contrast, FCC was mainly dependent on the disease duration (p < 0.0001; t-test). The presence of any complication cluster correlated with the need for surgery (p < 0.01; X2-test). However, only ICC correlated with a prolonged hospital stay (p < 0.05; t-test). CONCLUSIONS: ICC is mainly dependent on alcohol abuse. In contrast, FCC and PIC are mainly dependent on the disease duration. The etiology and disease duration can be used as predictors of the course of disease to provide individual treatment and surveillance strategies.

Spontaneous bacterial peritonitis caused by Listeria monocytogenes: A rare infection with very high leukocyte counts in ascitic fluid-case report and review of the literature.

We present a rare case of Listeria monocytogenes-induced spontaneous bacterial peritonitis (SBP) in cirrhosis. Examination of the patient's peritoneal fluid revealed an extremely high leukocyte count. We suspect, that the patient belongs to 1% of individuals in which Listeria monocytogenes is part of the intestinal flora. Cephalosporins as empiric antibiotics have a Listeria gap. A combination of aminopenicillin and aminoglycoside is recommended. Therefore, early microbiological diagnosis from ascites and blood is essential. Listeria should be considered as a rare cause of SBP, especially in case of very high leukocyte count in peritoneal fluid or lack of response to empiric therapy.

Genetic Mouse Models to Study Pancreatic Cancer-Induced Pain and Reduction in Well-Being.

In addition to the poor prognosis, excruciating abdominal pain is a major challenge in pancreatic cancer. Neurotropism appears to be the underlying mechanism leading to neuronal invasion. However, there is a lack of animal models suitable for translationally bridging in vitro findings with clinical trials. We characterized KPC (KrasG12D/+; Trp53R172H/+; P48-Cre) and KPPC (KrasG12D/+; Trp53R172H/R172H; P48-Cre) mice with genetically determined pancreatic ductal adenocarcinoma (PDAC) and compared them with an orthotopic pancreatic cancer mouse model, healthy littermates and human tissue. We analyzed behavioral correlates of cancer-associated pain and well-being, and studied neuronal remodeling and cytokine expression. Histologically, we found similarities between KPC and KPPC tissue with human samples. Compared to healthy littermates, we detect nerve fiber hypertrophy, which was not restricted to a certain fiber type. Interestingly, while KPPC mice showed significantly reduced well-being, KPC mice emerged to be better suited for studying long-lasting cancer pain that emerges over a slow course of tumor progression. To address the neuroinflammatory correlate of loss of well-being, we studied cytokine levels in KPPC mice and observed a significant upregulation of CXCL16, TNFRSF5, CCL24, CXCL1, CCL22, CLL20 and CX2CL1. In summary, we demonstrate that the KPC mouse model is best suited to studying cancer pain, whereas the KPPC model can be employed to study cancer-associated reduction in well-being.

[Prevention of gastrointestinal cancer]. / Prävention gastrointestinaler Tumore.

Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.

Association between Pancreatic Burnout and Liver Cirrhosis in Alcoholic Chronic Pancreatitis.

BACKGROUND/OBJECTIVES: In chronic pancreatitis (CP), progressive fibrosis of the pancreas leads to exocrine and endocrine insufficiency and, finally, to pancreatic burnout. Alcohol consumption is associated with fibrosis in the pancreas and the liver, and the activation of stellate cells plays a central role in the induction of fibrosis in both organs. However, the relationship between pancreatic burnout and liver cirrhosis (LC) is still poorly understood in patients with alcoholic CP (ACP). METHODS: We performed a single-center, retrospective, cross-sectional study with 537 CP patients. We analyzed the clinical presence of early and advanced pancreatic burnout and stated LC in cases of typical alterations in histology, liver stiffness measurement, cross-sectional imaging, or ultrasound. We analyzed further clinical parameters. RESULTS: The frequency of advanced pancreatic burnout was 6.5% for ACP (20/306) and 4% for non-ACP (8/206; p = 0.20; χ2 test). Advanced pancreatic burnout was not associated with the amount of alcohol consumption (p = 0.34) but with the disease duration (p = 0.0470) and rate of calcification (p = 0.0056). Furthermore, advanced pancreatic burnout was associated with LC (p < 0.0001) but cannot be explained by the amount of alcohol consumption. In ACP with alcohol consumption >80 g/day, an isolated LC was significantly more frequently detectable (14%, without pancreatic burnout) than an isolated advanced pancreatic burnout (1%, without LC). These results were confirmed by multivariable analyses. CONCLUSIONS: We identified a close association between LC and pancreatic burnout. The disease duration positively correlates with the development of pancreatic burnout. The liver seems to be more vulnerable to alcohol than the pancreas.

Pain Management in Chronic Pancreatitis: Summary of Clinical Practice, Current Challenges and Potential Contribution of the M-ANNHEIM Classification.

Abdominal pain, diarrhea with weight loss, and endocrine insufficiency represent the dominant symptoms of chronic pancreatitis (CP). High intensity of pain and constant pain have been shown to reduce quality of life in CP and may result in disability and increased health resource utilization. Various basic challenges and unanswered questions still exist regarding the treatment of pain in CP. Recently, limited evidence has been gained that early surgery for painful disease might be associated with better treatment results. Thus, timing of pancreatic surgery in painful disease represents a major issue that needs to be clarified in future studies. In this context, surveillance of patients is necessary in clinical practice. It appears that a generally accepted classification of the disease represents a major requirement for inter-institutional comparison of data with future progress in clinical research. Among recently proposed classification systems, the M-ANNHEIM classification system of CP with its recently presented M-ANNHEIM Surgery Score might be a useful tool to picture the course of the disease and to monitor treatment results. Future research is required to clarify the possible role of this system in the management of pain in CP. In the present article, we provide an overview of current status, challenges, and unanswered questions in the treatment of pain in CP, and we demonstrate the potential benefits of the M-ANNHEIM classification system in the management of painful CP.

Mechanical sensitization, increased axonal excitability, and spontaneous activity in C-nociceptors after ultraviolet B irradiation in pig skin.

ABSTRACT: Ultraviolet B (UVB) irradiation induces hyperalgesia in human and animal pain models. We investigated mechanical sensitization, increase in axonal excitability, and spontaneous activity in different C-nociceptor classes after UVB in pig skin. We focused on units with receptive fields covering both irradiated and nonirradiated skin allowing intraindividual comparisons. Thirty-five pigs were irradiated in a chessboard pattern, and extracellular single-fibre recordings were obtained 10 to 28 hours later (152 fibers). Units from the contralateral hind limb served as a control (n = 112). Irradiated and nonirradiated parts of the same innervation territory were compared in 36 neurons; low threshold C-touch fibers (n = 10) and sympathetic efferents (n = 2) were unchanged, but lower mechanical thresholds and higher discharge frequency at threshold were found in mechanosensitive nociceptors (n = 12). Half of them could be activated with nonnoxious brush stimuli in the sunburn. Four of 12 mechanoinsensitive nociceptors were found sensitized to mechanical stimulation in the irradiated part of the receptive field. Activity-dependent slowing of conduction was reduced in the irradiated and in the nonirradiated skin as compared with the control leg, whereas increased ability to follow high stimulation frequencies was restricted to the sunburn (108.5 ± 37 Hz UVB vs 6.3 ± 1 Hz control). Spontaneous activity was more frequent in the sunburn (72/152 vs 31/112). Mechanical sensitization of primary nociceptors and higher maximum after frequency are suggested to contribute to primary hyperalgesia, whereas the spontaneous activity of silent nociceptors might offer a mechanistic link contributing to ongoing pain and facilitated induction of spinal sensitization.

Maximum axonal following frequency separates classes of cutaneous unmyelinated nociceptors in the pig.

KEY POINTS: C-nociceptors are generally assumed to have a low maximum discharge frequency of 10-30 Hz. However, only mechano-insensitive 'silent' C-nociceptors cannot follow electrical stimulation at 5 Hz (75 pulses) whereas polymodal C-nociceptors in the pig follow stimulation at up to 100 Hz without conduction failure. Sensitization by nerve growth factor increases the maximum following frequency of 'silent' nociceptors in pig skin and might thereby contribute in particular to intense pain sensations in chronic inflammation. A distinct class of C-nociceptors with mechanical thresholds >150 mN resembles 'silent' nociceptors at low stimulation frequencies in pigs and humans, but is capable of 100 Hz discharge and thus is suited to encode painfulness of noxious mechanical stimuli. ABSTRACT: Using extracellular single-fibre recordings from the saphenous nerve in pig in vivo, we investigated peak following frequencies (5-100 Hz) in different classes of C-nociceptors and their modulation by nerve growth factor. Classes were defined by sensory (mechano-sensitivity) and axonal characteristics (activity dependent slowing of conduction, ADS). Mechano-insensitive C-nociceptors (CMi) showed the highest ADS (34% ± 8%), followed only 66% ± 27% of 75 pulses at 5 Hz and increasingly blocked conduction at higher frequencies. Three weeks following intradermal injections of nerve growth factor, peak following frequency increased specifically in the sensitized mechano-insensitive nociceptors (20% ± 16% to 38% ± 23% response rate after 72 pulses at 100 Hz). In contrast, untreated polymodal nociceptors with moderate ADS (15.2% ± 10.2%) followed stimulation frequencies of 100 Hz without conduction failure (98.5% ± 6%). A distinct class of C-nociceptors was exclusively sensitive to strong forces above 150 mN. This class had a high ADS (27.2% ± 7.6%), but displayed almost no propagation failure even at 100 Hz stimulation (84.7% ± 17%). Also, among human mechanosensitive nociceptors (n = 153) those with thresholds above 150 mN (n = 5) showed ADS typical of silent nociceptors. C-fibres with particularly high mechanical thresholds and high following frequency form a distinct nociceptor class ideally suited to encode noxious mechanical stimulation under normal conditions when regular silent nociceptors are inactive. Sensitization by nerve growth factor increases maximum discharge frequency of silent nociceptors, thereby increasing the frequency range beyond their physiological limit, which possibly contributes to excruciating pain under inflammatory conditions.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

CXCL10 and CCL21 Promote Migration of Pancreatic Cancer Cells Toward Sensory Neurons and Neural Remodeling in Tumors in Mice, Associated With Pain in Patients.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by excruciating pain, which has been associated with attraction of cancer cells and their invasion of intrapancreatic sensory nerves. Neutralization of the chemokine CCL2 reduced cancer-associated pain in a clinical trial, but there have been no systematic analyses of the highly diverse chemokine families and their receptors in PDAC. METHODS: We performed an open, unbiased RNA-interference screen of mammalian chemokines in co-cultures of mouse PDAC cells (K8484) and mouse peripheral sensory neurons, and confirmed findings in studies of DT8082 PDAC cells. We studied the effects of chemokines on migration of PDAC cell lines. Orthotopic tumors were grown from K8484 cells in mice, and mice were given injections of neutralizing antibodies against chemokines, antagonists, or control antibodies. We analyzed abdominal mechanical hypersensitivity and collected tumors and analyzed them by histology and immunohistochemistry to assess neural remodeling. We collected PDAC samples and information on pain levels from 74 patients undergoing resection and measured levels of CXCR3 and CCR7 by immunohistochemistry and immunoblotting. RESULTS: Knockdown of 9 chemokines in DRG neurons significantly reduced migration of PDAC cells towards sensory neurons. Sensory neuron-derived CCL21 and CXCL10 promoted migration of PDAC cells via their receptors CCR7 and CXCR3, respectively, which were expressed by cells in orthotopic tumors and PDAC specimens from patients. Neutralization of CCL21 or CXCL10, or their receptors, in mice with orthotopic tumors significantly reduced nociceptive hypersensitivity and nerve fiber hypertrophy and improved behavioral parameters without affecting tumor infiltration by T cells or neutrophils. Increased levels of CXCR3 and CCR7 in human PDAC specimens were associated with increased frequency of cancer-associated pain, determined from patient questionnaires. CONCLUSIONS: In an unbiased screen of chemokines, we identified CCL21 and CXCL10 as proteins that promote migration of pancreatic cancer cells toward sensory neurons. Inhibition of these chemokines or their receptors reduce hypersensitivity in mice with orthotopic tumors, and patients with PDACs with high levels of the chemokine receptors of CXCR3 and CCR7 had increased frequency of cancer-associated pain.

Analysis of the Course of Chronic Pancreatitis: Pancreatic Burnout Rates Are Only Increased in a Subgroup of Patients With Alcoholic Chronic Pancreatitis.

OBJECTIVES: The pancreatic burnout hypothesis postulated an increasing absence of pain with simultaneous functional insufficiency in advanced stages of chronic pancreatitis (CP). However, the underlying data remain scarce and contradictory. We aimed to analyze, first, the frequency of a pancreatic burnout in CP, and, second, its association with etiological risk factors. METHODS: We performed a multicenter, retrospective, cross-sectional study with 741 patients with CP categorized according to the M-ANNHEIM classification. Pancreatic burnout was defined by different combinations of exocrine or endocrine insufficiency with partial or complete absence of abdominal pain. RESULTS: The frequency of a pancreatic burnout increased with prolonged disease duration and was observed in a maximum of 38% of patients after 20 years. Development of a pancreatic burnout was significantly associated with alcohol consumption (P < 0.05, Mann-Whitney U test), but not with other etiological risk factors. After a disease duration of more than 10 years, the likelihood of a burnout was 8 times higher in alcoholic CP than in nonalcoholic CP (95% confidence interval, 1.5-42.0; P = 0.015, logistic regression analysis). CONCLUSIONS: A pancreatic burnout does not regularly occur in CP. Increased burnout rates are only observed in patients with alcoholic CP.

Clinical Course of Chronic Pancreatitis in Elderly Patients.

BACKGROUND: Several guidelines recommend the risk-adapted monitoring of patients with chronic pancreatitis (CP). However, dedicated risk stratification is widely missing in CP. Elderly-CP (disease onset with 60 or more years of age) may represent a subgroup of CP subjects with a distinct course of disease. AIMS: We aimed to investigate the clinical presentation of elderly-CP, and if elderly-CP requires an adapted monitoring. METHODS: Seven hundred forty one patients with CP were analyzed in a multicenter (Mannheim/Germany, n = 537; Gießen/Germany, n = 100; Donetsk/Ukraine, n = 104), cross-sectional, retrospective study and classified according to the M-ANNHEIM classification. RESULTS: The frequency of elderly-CP was 20% (148/741). In comparison with non-elderly-CP, elderly-CP was less frequently caused by alcohol and nicotine dependency or genetic mutations. In contrast, the frequency of efferent duct abnormalities (p = 0.009, chi-square test) and idiopathic CP (p < 0.0001, chi-square test) increased significantly. The presence of multiple risk factors was found less frequently in elderly-CP than in non-elderly patients (p < 0.0001; chi-square test). Furthermore, elderly-CP was associated with increased rates of pseudocysts (p = 0.0002; chi-square test), endocrine insufficiency (p = 0.001; chi-square test), and the absence of pain (p = 0.04; chi-square test) in the first year of the disease. CONCLUSION: In elderly-CP, the course of disease significantly differs from non-elderly-CP. Therefore, individualized monitoring strategies for elderly-CP might be necessary.

Clinical evaluation of the M-ANNHEIM classification: Development of the M-ANNHEIM-Surgery-Score as a new tool to monitor patients with chronic pancreatitis.

OBJECTIVES: The M-ANNHEIM classification of chronic pancreatitis (CP) stratifies degrees of disease severity according to the M-ANNHEIM-Severity-Score. We aimed to demonstrate the clinical usefulness of the M-ANNHEIM-Severity-Score in quantifying and predicting the frequency of pancreatic surgery, and to establish the M-ANNHEIM-Surgery-Score as a simplified system for patient surveillance regarding the demand of pancreatic surgery. METHODS: We performed a retrospective, cross-sectional study with 741 CP patients (Mannheim/Germany, n = 537; Gießen/Germany, n = 100; Donetsk/Ukraine, n = 104) categorized according to the M-ANNHEIM classification. RESULTS: We observed a significantly higher M-ANNHEIM-Severity-Score in patients that were classified within 7 days preceding pancreatic surgery than in individuals that did not require surgery (p < 0.001, Mann-Whitney-U-test). Using a logistic regression analysis with all variables of the M-ANNHEIM-Severity-Score, we established the M-ANNHEIM-Surgery-Score as a simplified new tool to identify patients that may require surgery. A receiver operating characteristic-analysis revealed a cut-off-value of 9 points within the M-ANNHEIM-Surgery-Score to identify these individuals (sensitivity 78.7 %, specificity 91 %). Based on the M-ANNHEIM-Surgery-Score, we defined three categories for demand of surgery with frequencies of pancreatic operations of 1.6 % (n = 7/440) in the "Baseline-Demand"-category, 7 % (n = 12/172) in the "Low-Demand"-category (p < 0.0001, Chi-square-test, OR 4.6, Confidence Interval (CI) 1.8 - 12), and 54 % (n = 70/129) in the "High-Demand"-category (p < 0.0001, OR 73, CI 32 - 167). Patients that were categorized for the "High-Demand"-category, but were not operated on, had a significantly increased ratio of clinical features that hamper performance of surgery (p < 0.001, Chi-square-test). CONCLUSIONS: The M-ANNHEIM-Surgery-Score represents a useful tool to monitor patients with CP and to estimate the demand of surgery in CP.

Prevalence of inflammatory bowel disease in alcoholic, non-alcoholic and autoimmune pancreatitis.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) frequently reveal features of pancreatic inflammation. However, the prevalence of IBD in patients with alcoholic pancreatitis (AP) and nonalcoholic pancreatitis (NAP) has not yet been determined, and the prevalence of IBD in patients with autoimmune pancreatitis (AiP) from Germany is unknown. AIMS: Thus, we aimed, first, to determine the prevalence of IBD in AP, NAP, and AiP from a tertiary center in Germany and, second, to characterize patients with AiP and IBD. METHODS: We performed a retrospective cross-sectional study to determine the prevalence of IBD in patients with different forms of pancreatitis presenting to our clinic. RESULTS: Compared to the general population and to a control group with viral hepatitis from our clinic, we observed the most significant increase of IBD in patients with AiP (n = 3/28; p < 0.0001 vs. general population, binomial proportion test; p = 0.0112 vs. hepatitis group, Fisher's exact test), followed by a significant increase in subjects with NAP (n = 11/278; p < 0.0001 vs. general population, binomial proportion test; p = 0.0338 vs. hepatitis group, Fisher's exact test). A review of previous studies on the prevalence of IBD among patients with AiP revealed a combined prevalence of 12 % (n = 43/355). Type 2 AiP is significantly more often associated with IBD than type 1 AiP (n = 28/48, 58 % vs. n = 7/129, 5 %; combined patient cohort, p < 10E - 12; Fisher's exact test). CONCLUSIONS: Immune-mediated mechanisms related to IBD may participate in the development of AiP, especially AiP type 2, and may also increase the risk for the development of other forms of pancreatic inflammation.

Monitoring and predicting disease activity in autoimmune pancreatitis with the M-ANNHEIM-AiP-Activity-Score.

BACKGROUND & OBJECTIVES: Autoimmune pancreatitis (AiP) is treated by immunosuppressive therapy. Exact description of disease activity of AiP is essential in clinical practice and research, but a score to describe the disease activity is missing. Thus, we aimed to establish an activity score of AiP. METHODS: We retrospectively studied long-term disease courses of 29 patients with AiP (Mannheim, Germany), receiving corticosteroid treatment (CST) by analyzing 613 treatment appointments. Two assumptions were made: First, disease activity is higher at emergency treatments; second, disease activity drops under CST. In all patients, we evaluated established activity- and classification-systems of chronic pancreatitis (cP). Based on the most suitable system, we established an activity score of AiP by including AiP-specific parameters identified from our long-term disease courses and the literature. The new AiP-specific activity score was validated in an external cohort of 14 patients with AiP (Stockholm, Sweden). RESULTS: Within published activity indexes of cP, the M-ANNHEIM-classification most significantly correlated with emergency- and treatment-dependent disease activities (p < 0.001 and p < 0.01, conditional-logistic-regression-analysis). Significant correlations of disease activity were found for several clinical parameters (biliary involvement, extrapancreatic lesions, acute pancreatitis, focal pancreatic mass, pancreatic sausage/mass, focal enlargement, ascites; p < 0.05, Wilcoxon-signed-rank-test). Based on these data and disease features from the literature, the M-ANNHEIM-AiP-Activity-Score (MAAS) was established. CST-induced reduction of MAAS disease activity of more than 60% was associated with lower relapse rates (p < 0.05; Chi-Square-test). The results were validated in the external patient cohort. CONCLUSION: The MAAS might represent a useful tool to monitor AiP.