Review of current therapy of pancreatic pseudocysts.

BACKGROUND AND AIMS: Therapeutic interventions for complicated pancreatitis, especially in pseudocysts and walled-off necroses as a sequel of necrotizing pancreatitis, have a long history. Originally a stronghold of classical surgery and radiology, in the last two decades this was increasingly supplemented by endoscopy, often with adjuvant percutaneous drainage, mostly reducing open surgery to a salvage intervention in case of failure and complication. This study aims to evaluate and compare the current therapeutic options for pancreatic fluid collections, especially pseudocysts. METHODS: Systematic literature search via MedLine and Pubmed was performed with comprehensive tabulations of original publications of the endoscopic, surgical and percutaneous therapeutic interventions in pancreatic pseudocysts and WON in the last 27 years. Only studies including more than 10 cases were further analysed. The results with regard to complications, outcome, recurrence and mortality were analysed for each approach, the risk of bias was assessed and a conclusive statement was made. RESULTS: The initial literature search identified 46 studies. 12 studies had to be excluded because the number of individuals included was too low. 34 endoscopic, 8 surgical and 8 percutaneous studies were further analysed, leading to a number of 2485 patients in this review. The short-term clinical success was 85 % for the endoscopic approach, 83 % for surgery and 67 % for the percutaneous intervention. The complication rates were 16 %, 45 % and 34 % for endoscopic, surgical and percutaneous therapy, respectively. Typical complications were hemorrhage, infection, perforation and, especially in the percutaneous approach, pancreatocutaneous fistulisation. CONCLUSION: According to the high success and low complication rates the endoscopic intervention appears as the most efficient method. But each method has its own indications, restrictions and therefore patient groups. Therefore it is reasonable to consider all the available methods in a productive interdisciplinary manner for the ultimate benefit of the patient in the future.

Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c).

BACKGROUND: Diabetes mellitus secondary to pancreatic diseases is a condition seldom thought of in clinical practice. Yet, a high percentage of exocrine pancreatic insufficiency has been reported for the general population and especially for diabetic subjects. Thus, we investigated the prevalence of diabetes mellitus due to pancreatic diseases. METHODS: In this study, we investigated 1868 patients diagnosed with diabetes mellitus who had been admitted to our hospital during the last 24 months. Patient data were diligently studied, and patients were reclassified according to the diabetes classification as proposed by the American Diabetes Association. RESULTS: Among 1868 subjects, 172 patients could be classified as type 3c diabetes mellitus (9.2%). Among these were 135 diagnosed with chronic pancreatitis (78.5%), 12 with hereditary haemochromatosis, 14 with pancreatic cancer and 7 with cystic fibrosis. Thus, diabetes mellitus due to chronic pancreatitis occurred in this collective in 7.2% of all diabetic subjects. Misclassification of these patients was very common. Only 51.2% (88/172) were initially classified correctly. Most type 3 diabetes patients were initially misclassified as type 2 diabetes (69/84). CONCLUSIONS: Diabetes mellitus secondary to pancreatic diseases (especially chronic pancreatitis) seems more common than generally believed with a prevalence of 9.2% among the subjects studied here. Because the awareness of this diabetes type is poor, misclassification is quite frequent. A common problem seems to be the differentiation between type 2 and type 3. Yet, the right classification of diabetes mellitus is important, because there are special therapeutic options and problems in patients with diabetes secondary to pancreatic diseases.

Profile of gastrointestinal involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.

Determinants of Exocrine Pancreatic Function as Measured by Fecal Elastase-1 Concentrations (FEC) in Patients with Diabetes mellitus.

OBJECTIVE: Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus. METHODS: The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation. RESULTS: FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%), 167 as type-2 (54.4%), and 88 patients met the diagnostic criteria of type-3 (28.7%). Fourteen patients could not be classified because of lacking information (4.6%). CONCLUSIONS: Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.

Parathormone levels and Vitamin D metabolism in female patients with various grades of fecal elastase 1 deficiency.

BACKGROUND: There are still too few conclusive reports about conspicuous parathormone (PTH) and Vitamin D metabolism in patients with fecal elastase 1 deficiency or any connection of the calcium metabolism to the severity of exocrine pancreas insufficiency. METHODS: Between March 1998 and September 2002, we investigated on 240 female patients with fecal elastase 1 deficiency at an average age of approx. 56.4 years and suffering from meteorism and weight loss as well as on age matched 80 healthy female controls. Serum levels of PTH, total calcium, D subset3-vitamins, calcitriol and calcefediol, as well as the concentration of fecal elastase 1 were determined in patients and controls. RESULTS: In 240 female patients with deficiency of fecal elastase 1 only two patients show milder cases of new diagnosed primary hyperparathyroidism. Calcitriol was markedly decreased (14.3 +/- 6.1 and 20.7 +/- 9.4 pg/ml) compared to controls (41.8 +/- 8.3 pg / ml) ( p < 0.01). Calcefediol was not significantly different within the various elastase-groups (p = 0.07). Nevertheless, vitamin D subset3 and fecal elastase 1 in patients correlated significantly (p < 0.01) and, compared to controls, both were extremely low (means in patients. Both D subset3-vitamins in patients were significantly lower when elastase 1 in feces was under 200 microg/g compared to the others (for calcitriol p < 0.05, for calcefediol p < 0.05). CONCLUSION: In female patients elastase 1 in feces confirm the grade of vitamin D supply, and thus show a vitamin D subset3-deficiency, depending on the loss of stool content. There seems to be a connection here between the loss of exocrine function and may be even the characteristic of sterol-binding of elastase 1 in the pancreas, which seems to be relevant for vitamin D-supply.

Alterations of vitamin D3 metabolism in young women with various grades of chronic pancreatitis.

BACKGROUND: There are still too few conclusive reports about conspicuous vitamin D-deficiency in young female patients with chronic pancreatitis, or any connection of the deficiency to the severity of the disease. Therefore the aim of this study was to examine marker of vitamin D3 metabolism in female patients with episode of biliary pancreatitis to determine if increased severity of the disease would correlate with impaired vitamin D3 metabolism. METHODS: Between 1996 and 2003, we investigated 53 premenopausal patients with an average age of approximately 33 years suffering from an episode of chronic pancreatitis, as well as 30 female healthy controls with an average age of 32.4 years. The severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreaticography (ERCP) and assigned to 1 of 3 grades based on the Cambridge classification. Additional parameter assessed were demographics, smoking, consumption of alcohol and CD-transferrin, fasting metabolic parameters, biochemical markers of vitamin D3 metabolism and fecal elastase 1. None of the patients received hormone replacement therapy, Vitamin D or Calcium-supplementation. RESULTS: The serum levels of 1,25-dihydroxyvitamin D [1,25(OH2)D] were significantly reduced compared to female healthy controls. Fecal elastase 1 correlated with this classification of severity of chronic pancreatitis (p < 0.01). Furthermore, fecal elastase 1 of patients correlated the same way with both D-vitamins (p <0.01). The level of both D3 vitamins in patients were significantly lowered when the content of fecal elastase 1 was under 200 microg/g compared to the others [for 1,25-(OH2)D3 p < 0.01; 25-OH- D3 p < 0.01]. CONCLUSION: Premenopausal patients with chronic pancreatitis are at risk of developing decreased levels of 1,25(OH2)D3. This fact may contribute to a negative calcium balance and alteration of bone metabolism. Therefore, ERCP and fecal elastase 1 verify the severity grade of a chronic pancreatitis, and thus show a vitamin D3 deficiency in young women, depending on the progress of disease.

Measurement of fecal pyruvate kinase type M2 (tumor M2-PK) concentrations in patients with gastric cancer, colorectal cancer, colorectal adenomas and controls.

BACKGROUND: The determination of Tumor M2 Pyruvate Kinase (Tumor M2-PK) in EDTA plasma has been described as a tumor marker in a variety of different tumor types. Since most GI tumors grow intraluminally, it appeared interesting to determine whether Tumor M2-PK is detectable in the feces of tumor patients. MATERIALS AND METHODS: Measurements were performed with a commercially available ELISA (ScheBo Biotech AG, Giessen, Germany) modified for fecal analysis. Samples of controls, GI cancer and adenoma patients were tested. RESULTS: Fecal Tumor M2-PK concentrations could be quantified. A significant difference between cancer patients and controls was found. The highest concentrations were observed in colorectal cancer. However, fecal Tumor M2-PK was not detectable in 5 tumor patients. CONCLUSION: The measurement of fecal Tumor M2-PK concentrations might provide an interesting screening tool for colorectal cancer. Further studies comparing the determination of Tumor M2-PK in stool to occult blood in stool are in progress.

Fecal pyruvate kinase concentrations (ELISA based on a combination of clone 1 and clone 3 antibodies) for gastric cancer screening.

BACKGROUND: Recently we were able to demonstrate that Tumor M2 Pyruvate Kinase (Tumor M2-PK) is detectable in the feces of patients with gastrointestinal (GI) cancer. In this study an ELISA based on a different combination of antibodies was used to investigate stool samples of GI cancer patients. PATIENTS AND METHODS: The ELISA (ScheBoBiotech AG, Giessen, Germany) was based on one antibody specific for Tumor M2-PK and a second antibody reacting with Tumor M2-PK, M1-PK and the tetrameric M2-PK. Stool samples of healthy controls, patients with inflammatory bowel disease (IBD) and different kinds of GI cancer were tested. RESULTS: Compared to controls, samples of IBD or different tumors did not show significant differences, except those patients with gastric cancer (elevated fecal PK in 80% (p = 0.005)). CONCLUSION: If the present results can be confirmed in larger patient samples, this new test might provide an excellent screening tool for gastric cancer.

Tumor M2-pyruvate kinase: a promising tumor marker in the diagnosis of gastro-intestinal cancer.

The diagnostic value of pyruvate-kinase type tumor M2 (Tumor M2-PK) has been investigated in different tumors, and showed interesting results in cases of renal cancer, pancreatic cancer, lung cancer and some cases of gastric cancer. In this study we investigated EDTA-plasma of 68 patients with gastrointestinal cancer, 22 patients with inflammatory bowel disease (IBD) and 60 healthy controls. Sensitivity of Tumor M2-PK was 70.6% for all GI-tumors, that of CA19-9 was 55.4% and that of CEA was 53.3%. In pancreatic cancer CA19-9 showed the best sensitivity. In oesophageal/gastric cancer Tumor M2-PK was most sensitive and in colorectal cancer CEA and Tumor M2-PK showed the best results. The specificity of Tumor M2-PK was 90-96, 7%. In IBD some individuals showed elevated Tumor M2-PK levels but there was no correlation to CRP or to the clinical activity score. The results indicated that Tumor M2-PK might be a valuable marker in gastrointestinal cancer.

Prospective evaluation of novel system for jejunal feeding.

BACKGROUND: Enteral nutrition should be restored immediately after trauma, acute lesion, or surgical intervention. Nutrition through nasogastric tubes is often not feasible in patients in the posttraumatic state in medical intensive care units because of recurrent episodes of gastroesophageal reflux and subsequent aspiration due to gastric paresis. Placement of nasojejunal tubes with available techniques is unreliable. METHODS: We developed a new combined catheter system for jejunal delivery and simultaneous drainage of gastric juice (Cath-in-Cath, PreOx-RS, Germany). CONCLUSION: In this article, this new tube system is presented. The safety and excellent efficacy of the novel system for enteral nutrition therapy are reported in the first series of patients worldwide.

Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus.

Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 patients with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenetic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far.

Liquid pancreatic enzyme therapy for a patient with short bowel syndrome and chronic pancreatitis in a complicated case of Crohn's disease.

The case of a 45 year old female with multiple complications of Crohn's disease is reported. After multiple resections in the gastrointestinal tract she had been suffering from short bowel syndrome and severe malnutrition. With a special continuous gastric tube feeding system, she was able to maintain her weight for years. In the beginning of 1997 the enteral nutrition was not longer tolerated for an exacerbation of chronic pancreatitis. There was a weight loss, permanent pain and total parenteral nutrition had to be performed. In this situation a new liquid preparation of pancreatic enzymes which had been tested in the laboratory before, was used for continuous enzyme replacement via gastric tube. In combination with this enzyme preparation, enteral nutrition could successfully be started again.

Octreotide in the prevention of pancreatic damage induced by endoscopic sphincterotomy.

Somatostatin and the long acting analogue octreotide have been proposed as a therapeutic agent in acute pancreatitis and for the prophylaxis of pancreatic damage by ERCP and EST for their ability to reduce exocrine pancreatic secretion. However, clinical trials could not show significant beneficial effects in acute pancreatitis and ERCP. In patients undergoing EST, data remained controversial, most authors describing positive effects of prophylaxis. In this study we investigated the use of octreotide prophylaxis to reduce EST-induced pancreatic damage in a randomised, double blind trial. 94 consecutive ERCP/EST-patients were randomised to receive either octreotide 200 microgram s.c. or placebo 3 times daily, starting the night before endoscopic procedures. In 59 patients EST was performed. Blood samples were collected before and 40 min, 2 hrs, 6 hrs, 24 hrs, 48 hrs and 72 hrs after the endoscopic procedures. Samples were analysed for pancreatic serum enzymes, acute phase proteins and blood counts. A clinical pain score was investigated. Post-EST-pancreatitis (amylase > 3x upper limit and persistent abdominal pain) was diagnosed in 3 patients in the treatment group, in 4 patients in the placebo group. There were no significant differences in the time-courses of serum enzymes or acute phase proteins in-between the groups, nor in the pain-score. According to these data, prophylactic octreotide application does not prevent acute pancreatic damage induced by endoscopic sphincterotomy.

Influence of cholesterol and fat in food on indirect parameters of exocrine pancreatic function.

Fecal elastase 1, chymotrypsin activity, and fat content in stool are clinical parameters of exocrine pancreatic function. The aim of this study was to clarify the possible impact of extreme changes in diet on fecal enzyme concentration/activity, since extreme diets may lead to wrong conclusions in the diagnosis of pancreatic insufficiency. Twelve healthy test persons followed 4 diet phases, each with a duration of 6 days. The 4 diet phases were (1) nearly fat-free with a low-cholesterol content; (2) high in fat and low in cholesterol; (3) high in cholesterol deriving from meat, and (4) high in cholesterol deriving from eggs. At the end of each diet phase, a 72-hour stool collection was carried out to measure fecal elastase 1, chymotrypsin and fecal fat content. The results showed no significant changes after each of the 4 diet phases. The clinical parameters of fecal elastase 1 and chymotrypsin activity in stool do not seem to be significantly influenced by fat and cholesterol deriving from food.

[Pyruvate kinase M2 (tumor M2-PK) as a screening tool for colorectal cancer (CRC). A review of current published data]. / Pyruvatkinase M2 (Tumor M2-PK) im Stuhl als Screeningparameter für kolorektale Neoplasien. Eine Ubersicht über bisher publizierte Daten.

INTRODUCTION: Colonoscopy is currently supposed to be the best screening tool for colorectal cancer. However, the acceptance of the population is very poor although it has been included in screening programs in the German health system since 2002. Therefore, evaluation of additional screening tools seems to be of great interest. Recently testing for fecal occult blood (FOBT), genetic alterations or alterations in tumor metabolism (e.g., tumor M2-PK) are under investigation. METHODS: The use of M2-PK measurement in the feces has been reported in 6 studies until today. The data of these studies were analyzed and critically reviewed. RESULTS: The overall sensitivity of M2-PK is 77.9% concerning CRC. Specificity ranges from 74.3-83.3%. Overall sensitivity for adenomas is 45.9%, increasing to 61.1% for adenomas > 1 cm. A high percentage of positive results (90.4%) was also observed in patients with chronic inflammatory bowel disease. CONCLUSIONS: Compared to FOBT or genetic testing the M2-PK test seems to be superior for CRC screening. Concerning handling, effectiveness and analysis, M2-PK seems to be a good possibility for large scale-screening of colorectal carcinoma. It might even be used to detect larger adenomas. Elevated levels of M2-PK in patients with acute and/or chronic inflammatory bowel diseases are probably due to proliferation of epithelial cells and leucocytes in the inflammatory area.

[A rare combination of pheochromocytoma ans somatostatin-rich neuroendocrine tumor of Vater's papilla (carcinoid) in a patient with von Recklinghausen neurofibromatosis]. / Die seltene Kombination eines Phäochromozytoms und eines somatostatinreichen neuroendokrinen Tumors der Papilla Vateri (Karzinoid) bei einem Patienten mit Neurofibromatose von Recklinghausen (NvR).

A 74-year-old male suffering from Recklinghausen's fibromatosis (NvR) is reported. He presented with weight loss, cholestasis, endocrine and exocrine pancreatic insufficiency. These symptoms were caused by a neuroendocrine tumor of the ampulla of Vater containing somatostatin. The tumor induced an obstruction of both the common bile and the pancreatic duct. In addition to this uncommon tumor, a silent pheochromocytoma was found. The patient was treated by endoscopic papillotomy, substitution of pancreatic enzymes and additional enteral nutrition. After recovery no progression of the disease was observed over one year. A review of the literature shows that patients with neurofibromatosis are at high risk for periampullar tumors. In particular, somatostatin-rich carcinoids were previously documented. Pheochromocytomas are also quite prevalent in NvR. However the combination of NvR, pheochromocytoma and somatostatin-rich neuroendocrine tumors of the duodenum has only been reported a few times. An explanation for the high prevalence of neuroendocrine tumors in NvR might be the loss of neurofibromin, a tumor suppressor protein, which is the main product of the neurofibromatosis-l-gene.

Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer.

Proliferating cells, especially tumour cells, express a special isoenzyme of pyruvate kinase, termed M2-PK, which can occur in a tetrameric form with a high affinity to its substrate, phosphoenolpyruvate (PEP), and in a dimeric form with a low PEP affinity. In tumour cells, the dimeric form is usually predominant and is therefore termed Tumour M2-PK. The levels of Tumour M2-PK within tumours and in EDTA-plasma correlate with staging and the ability of the tumour cells to metastasise. Since most colorectal tumours grow intraluminally, it appeared interesting to determine whether Tumour M2-PK is detectable in the faeces of tumour patients. Stool samples were tested by ELISA from controls without colorectal cancer and colorectal cancer patients. Whereas Tumour M2-PK levels were low in the control group (mean value+/-s.e.m.: 3.3+/-0.4, n=144), they were high in the case of colorectal cancer (56.1+/-15.3, n=60). At a cutoff value of 4 U ml(-1), the sensitivity was 73%. TNM and Dukes' classification of the tumours revealed a strong correlation between faecal Tumour M2-PK levels and staging. The determination of Tumour M2-PK in faeces provides a new promising screening tool for colorectal tumours.

The commercially available ELISA for pancreatic elastase 1 based on polyclonal antibodies does measure an as yet unknown antigen different from purified elastase 1. Binding studies and clinical use in patients with exocrine pancreatic insufficiency.

The measurement of fecal elastase 1 concentrations by means of an ELISA based on monoclonal antibodies (mABs) highly specific for human elastase 1 (ELISA 1) has become an accepted indirect test of the exocrine pancreatic function during the last years. Its use has been demonstrated in many clinical studies including comparison with direct function tests and ERCP morphology. Recently, a new ELISA, also named "elastase 1" based on polyclonal antibodies (pABs; ELISA 2) became available. In the present investigation we performed binding studies with purified elastase 1 as well as studies on patients with exocrine insufficiency with both ELISAs. Surprisingly, the pABs on the solid phase (catcher antibodies) of ELISA 2 did not bind purified elastase 1. These antibodies seem to react with an as yet unknown antigen associated with elastase 1. Measurement of samples from patients suspected to suffer from exocrine insufficiency showed a weak correlation of both assays but higher levels in ELISA 2, resulting in false normal results even in some patients with pancreatic steatorrhea. Since the reference range used in both assays has been established using ELISA 1, ELISA 2 must be re-evaluated in comparison to direct function tests. ELISA 2 should be renamed, since obviously it does react with an antigen (antigens) different from elastase 1.

Pathological pancreatic exocrine function and duct morphology in patients with cholelithiasis.

Most authors claim alcohol consumption to be the only relevant reason for chronic pancreatitis. However, gallstones might cause this disease, as they do cause acute pancreatitis. In this study 91 gallstone patients and 94 age-matched controls were investigated concerning exocrine pancreatic function (fecal elastase-1 concentrations). Furthermore x-rays of 100 consecutive ERCP patients were evaluated for differences concerning pancreatic duct changes between patients with and without evidence of cholelithiasis. Pathological elastase 1 levels were more frequent in gallstone patients (30,8%) as compared to age-matched controls (19%). Symptoms such as upper abdominal pain, bloating, and fat intolerance were reported more often in gallstone patients. In ERCP of gallstone patients (N = 60), 77% were found to have chronic pancreatitis according to the Cambridge classification, while in nongallstone-patients (N = 32) 47% had chronic pancreatitis. In conclusion, according to these data a pathophysiological connection between gallstones and chronic pancreatitis appears to be probable.