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H Friess

Publications and source records attributed to H Friess.

At least 55 records · Page 3Linked to original sources
PubMed2004

Expression analysis of MAC30 in human pancreatic cancer and tumors of the gastrointestinal tract.

Meningioma-associated protein, MAC30, is a protein with unknown function and cellular localization that is differentially expressed in certain malignancies. In the present study, the expression of MAC30 in a variety of normal and cancerous human gastrointestinal tissues, with special emphasis on pancreatic tissues was analyzed. Quantitative RT-PCR was utilized to compare MAC30 expression levels. In situ hybridization and immunohistochemistry were carried out to localize MAC30 mRNA and protein expression in normal and cancerous tissue samples of the esophagus, stomach, colon and pancreas. Furthermore, the effects of TGF-beta on the transcription of MAC30 mRNA were examined in pancreatic cancer cells. MAC30 mRNA was expressed in a wide variety of normal human tissues, being most abundant in testicular and gastric tissue samples. MAC30 mRNA levels were significantly increased in breast and colon cancer, but significantly decreased in pancreatic and renal cancer. TGF-beta down-regulated MAC30 mRNA levels in certain pancreatic cancer cells. MAC30 protein was localized in normal pancreatic tissues, mainly in acinar and islet cells, and in normal colon, gastric and esophageal tissues especially in the mucosal cells. MAC30 was strongly present in tubular complexes in pancreatic cancer tissues but weak to absent in pancreatic cancer cells of primary tumors and metastases. In contrast, esophageal, gastric and colon tumors displayed strong MAC30 immunoreactivity in the cancer cells. In conclusion, MAC30 is expressed in various normal and diseased human tissues. MAC30 up-regulation in certain tumors and down-regulation in others suggests that this protein plays a distinct role in human malignancies.

Adult↗
PubMed2004

Duodenum preserving pancreatic head resection in the treatment of chronic pancreatitis.

Chronic pancreatitis is an inflammatory disease which is characterized by a progressive conversion of pancreatic parenchyma into fibrous tissue. Most frequent causes are alcohol over-consumption, beside anatomic variants such as pancreas divisum, cholelithiasis or individual genetic predisposition. The process of fibrotic transformation with consecutive loss of pancreatic parenchyma leads to exocrine insufficiency and maldigestion, and in advanced stage of the disease to diabetes mellitus. In addition to exocrine and endocrine malfunction, mechanical complications such as formation of pancreatic pseudocysts, duodenal and common bile duct obstruction occur. About 50% of the patients with chronic pancreatitis will need surgical intervention due to intractable chronic pain. Recent investigations suggest that the head of the pancreas triggers the chronic inflammatory process. Therefore, resection of this inflammatory mass must be regarded as the pivotal part of any surgical intervention. Radical techniques such as Whipple-procedure are undoubtedly successful regarding pain reduction. However, even in its pylorus preserving variant this technique is associated with a high postoperative morbidity due to large loss of pancreatic parenchyma and the loss of the duodenal passage. 30 years ago, H. G. Beger described for the first time the technique of duodenum preserving pancreatic head resection that better combines resection of the pancreatic head with low morbidity. Over the years different variations of the original Beger technique (Frey, Izbicky, Berne modification) have been developed, and the excellent results obtained with these techniques underline, that organ sparing procedures should be preferred in the surgical treatment of chronic pancreatitis.

Chronic Disease↗
PubMed2003

Comparison of histological features and inflammatory cell reaction in alcoholic, idiopathic and tropical chronic pancreatitis.

BACKGROUND: There is increasing evidence that immune mechanisms may be crucial in the development of alcoholic chronic pancreatitis. However, it is not known whether differences in underlying aetiology influence the inflammatory reaction in patients with chronic pancreatitis. The histological features and the pattern of inflammatory cell infiltration were studied in three aetiological forms of chronic pancreatitis: alcoholic, idiopathic and tropical pancreatitis. METHODS: Forty-three patients, ten with alcoholic, 12 with idiopathic and 21 with tropical chronic pancreatitis, were evaluated for the pattern of pancreatic inflammatory cell infiltration and histological features. Ten organ donors served as controls. Haematoxylin and eosin-stained tissue sections were used for histological evaluation. For immunohistochemical characterization of the inflammatory reaction, four antibodies-CD4, CD8, CD45 and CD68-were used. Quantitative evaluation of the various cell infiltrates was performed with computer-assisted image analysis. The inflammatory cell infiltration pattern was also evaluated. RESULTS: The degree of endophlebitis and the overall density of plasma cells were greater in tropical than in alcoholic chronic pancreatitis. The grade of intralobular fibrosis was significantly higher in tropical chronic pancreatitis compared with the idiopathic form. No significant quantitative differences in the specific cellular infiltrates (CD4, CD8, CD45, CD68) were observed in the three different groups. However, the perivascular inflammation number score was significantly higher in alcoholic compared with idiopathic pancreatitis (P = 0.037), and the perivascular inflammation area score was significantly lower in idiopathic than in alcoholic (P = 0.024) or tropical (P = 0.020) pancreatitis. CONCLUSION: Different aetiological forms of chronic pancreatitis result in similar histological features and a comparable inflammatory cell reaction, indicating that the disease, independent of the underlying aetiology, reaches a common immunological stage beyond which it appears to progress as a single distinctive entity.

Adult↗
PubMed2003

Microarray-based identification of differentially expressed growth- and metastasis-associated genes in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To improve diagnosis and treatment, key mechanisms of deregulated molecular functions have to be identified. Using microarray analysis, the expression patterns of 5600 human genes were assessed in PDAC by comparison with the normal pancreas and chronic pancreatitis (CP). The expression of 467 of 5600 genes was increased in PDAC in comparison to the normal pancreas, and the expression of 120 of these genes was not increased in CP. In addition, 341 of 5600 genes were expressed at decreased levels in PDAC tissues, of which 96 were decreased in comparison to both normal and CP tissues. Thus, a total of 808 of 5600 human genes were differentially expressed in pancreatic cancer. The identification of a large panel of altered genes in PDAC will stimulate additional studies that will lead to improved understanding of the molecular mechanisms underlying pancreatic malignant growth.

Adenocarcinoma↗
PubMed2003

[Central case management in surgery].

Up to now, in most surgical departments there has been no central patient management coordinating the admission, the diagnostic work-up, and the surgical procedures of patients with the resources available in the hospital. In future, however, it will be essential for surgical departments to establish such a central patient management, not only in view of the importance of patient-oriented medicine but also considering the planned introduction of diagnosis related groups. A central patient management will reduce preoperative and overall length of stay through adequate organisation and communication structures. In addition, a central patient management will make optimal use of the available resources in terms of operation rooms and hospital beds. In this article, we will present our basic concept of a central patient management in a surgical university department.

Diagnosis↗
PubMed2003

[Adjuvant and additive therapy for cancer of the pancreas].

Recent advances have been made in the treatment of pancreas cancer. Specialized pancreas centres have reported an increasing rate of resections with reduced postoperative mortality. On account of the highly aggressive nature of pancreas cancer, there is a great challenge in identifying effective therapy concepts for advanced stages of the cancer as well as for the development of resection-associated measures. As large-scale, randomised, controlled studies are lacking, the additive therapy concepts after resection do not have a sufficiently scientific basis. The ESPAC-1 study, which included 600 patients, surpassed all previous studies on adjuvant therapy for pancreas cancer. This study has shown,for example, that the most promising adjuvant chemotherapy with 5-fluorouracil and folic acid leads to an equal if not better result than the multimodal regimen. This regimen can be superseded with the use of Gemcitabine, which will be evaluated in the ESPAC-3 study that includes 990 patients from various European countries including Germany, as well as from Canada and Australia. Participation in the large, phase-3 study therefore plays a key role in the continued development of the management of pancreas cancer.

Antimetabolites, Antineoplastic↗
PubMed2003

[Surgical standard therapy for cancer of the pancreas].

Approximately 150,000 people worldwide and 40,000 people in Europe die each year of pancreatic cancer,making it one of the five leading causes of cancer-related death and one of the most aggressive human tumors. Resection is still the only option that offers a chance of cure for pancreatic cancer patients. Recent studies have highlighted the correlation between the number of pancreatic resections per year and postoperative mortality. Thus, large centers of pancreatic surgery have mortality rates below 5%, whereas centers with lower caseloads have mortality rates exceeding 10%. Standards have been established for the surgical treatment of pancreatic cancer;however, these are often not based on evidence derived from randomized, controlled studies. Resection for pancreatic cancer is carried out if there are no metastases present and if the tumor is locally resectable; i.e., if there is no complex vessel invasion. However, an isolated infiltration of the portal vein is not considered a contraindication for surgery. At present, there are no evidenced-based data available on palliative (R2) resections,which might be a therapeutic option in centers with low morbidity/mortality. Three randomized controlled trials clearly show that the pylorus-preserving Whipple is equal to the classical Whipple in terms of oncological effectiveness, morbidity, and quality of life. Therefore, the pylorus-preserving Whipple is increasingly considered the standard operation for tumors of the pancreatic head. Based on randomized trials, extended lymph node dissection cannot generally be recommended for pancreatic cancer. Further prospective, randomized, multicenter trials have to be carried out in the upcoming years to find new approaches in the therapy of pancreatic cancer and to establish evidence-based treatment strategies for this disease.

Adenocarcinoma↗
PubMed2003

Long-term expression of fibrogenic cytokines in radiation-induced damage to the internal anal sphincter.

BACKGROUND: There is accumulating evidence, both quantitative and qualitative, that pelvic irradiation affects anorectal function. However, the molecular mechanisms responsible for radiation-induced damage to the anal sphincter remain unclear. AIM: To determine the expression of transforming growth factor-beta 1 (TGF-beta 1) and its downstream effector connective tissue growth factor (CTGF) in the anal sphincter of a patient irradiated for prostate cancer. PATIENT: A 82 year-old patient developed a rectal adenocarcinoma and underwent an abdomino-perineal resection (APR), four years after receiving pelvic irradiation for prostate carcinoma. METHODS: Tissue sections of the anal sphincter were processed for histology. Immunostaining for TGF-beta 1 and CTGF were performed. RESULTS: CTGF and TGF-beta 1 immunoreactivity was detected in the irradiated anal sphincter, and was absent in controls. Immunoreactivity for both cytokines predominated in the internal sphincter. CTGF and TGF-beta 1 were preferentially detected in endothelial cells, myofibroblasts and fibroblasts; in addition, there was strong immunoreactivity for TGF-beta 1, but not for CTGF in smooth muscle cells of the anal canal. CONCLUSION: Four years after pelvic irradiation, radiation-induced damage appeared to affect predominantly the smooth muscle layer of the anal canal. The molecular mechanisms responsible for radiation-induced fibrosis to these tissues involve prolonged activation of TGF-beta 1 and its downstream effector CTGF.

Adenocarcinoma↗
PubMed2003

Pancreatic intraductal ultrasonography (IDUS) allows early diagnosis of pancreatic carcinoma in situ: a case report.

A 66-year-old woman was admitted with diarrhea, weight loss, slight recurrent abdominal pain, and raised serum amylase and lipase. Lactose intolerance was diagnosed, and treatment was begun. The symptoms diminished. However, slight back pain and elevated serum amylase and lipase levels persisted. A pancreatic tumor was then suspected. Ultrasound, spiral computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) examinations were inconclusive. Endoscopic retrograde cholangiopancreatography (ERCP) showed a slight narrowing of the pancreatic duct within the pancreatic body, and endoscopic ultrasound (EUS) revealed a 10 mm intrapancreatic lesion. Finally, intraductal ultrasonography (IDUS) reliably identified a small pancreatic tumor. The tumor was resected, and histology confirmed a well-differentiated adenocarcinoma in situ (UICC stage 0, TisN0M0). This case shows that using high-resolution imaging techniques such as EUS plus IDUS, small malignant pancreatic lesions can be detected at an early stage, when curative action is possible.

Aged↗
PubMed2003

[Operative management in the treatment of pancreatic cancer].

The carcinoma of the pancreas is one of the 10 leading causes of death in the Western countries. Because of the resistance of pancreatic cancer against radiation and/or chemotherapy surgery is still the only possibility for cure. However, about 80 % of patients with the diagnosis of pancreatic cancer are no more suitable for curative resection at the time of diagnosis because of local tumor infiltration or the presence of distant metastases. This is one reason for the unsatisfactory situation in terms of 5-year-survival rate of 3 to 24 %. In resectable tumors of the pancreas head the standard Whipple dominates still as the surgical method of choice. However, the pylorus preserving Whipple has been established as a surgical alternative to the classical Whipple. Other surgical procedures like extended or regional pancreatic resections, predominantly done by Japanese surgeons seem to fit the concept of radical resection. But compared to the classical Whipple or the pylorus preserving Whipple resection there is still no clear advantage in terms of long term survival. The prospective European multicenter study ESPAC-1 firstly demonstrated a survival advantage for adjuvant chemotherapy (5-FU and folic acid) but no gain for radiochemotherapy in the treatment of patients with R0 or R1 resected pancreatic cancer in terms of prolongation of mean survival (19.7 months vs. 14.0 months).

Antimetabolites, Antineoplastic↗
PubMed2003

COMP is selectively up-regulated in degenerating acinar cells in chronic pancreatitis and in chronic-pancreatitis-like lesions in pancreatic cancer.

BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized histomorphologically by progressive development of fibrosis and atrophy of the pancreatic parenchyma. Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin (TSP) family of extracellular glycoproteins that is expressed in CP tissues. In the present study, we characterized COMP mRNA and protein expression in the normal pancreas, chronic pancreatitis, and pancreatic cancer tissues. METHODS: 15 normal pancreatic tissues, 14 CP tissues and 14 pancreatic cancer tissues were analyzed by Northern blotting, Western blotting, in situ hybridization and immunohistochemistry. RESULTS: COMP mRNA and protein were detected at moderate to high levels in chronic pancreatitis tissues, at moderate levels in pancreatic cancer tissues, but at low levels in normal pancreatic tissues and in four pancreatic cancer cell lines. COMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. COMP protein was also present in the fibrotic tissue in CP. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues. CONCLUSION: COMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this gene in the course of acinar cell degeneration and dedifferentiation. COMP might thus serve as a marker for tissue destruction and disease activity in CP.

Adolescent↗
PubMed2003

Activity of raltitrexed and gemcitabine in advanced pancreatic cancer.

BACKGROUND: Gemcitabine has evolved as standard therapy in advanced pancreatic cancer since the demonstration of a significant clinical benefit. Phase II trials have shown that gemcitabine can be successfully combined with thymidylate synthase (TS) inhibitors such as continuous-infusion 5-fluorouracil (5-FU). However, continuous-infusion 5-FU is inconvenient because of the need for a central venous access. The aim of this study was to assess the efficacy and safety of gemcitabine in combination with raltitrexed (Tomudex), a novel and selective TS inhibitor that has the advantage of a 3-weekly treatment interval and manageable toxicity. PATIENTS AND METHODS: Chemotherapy-naïve patients with measurable advanced pancreatic cancer were treated with raltitrexed 3 mg/m(2) as a 15-min infusion on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, every 21 days. RESULTS: Twenty-five eligible patients (17 male, eight female) with metastatic (21 patients) or locally advanced (four patients) disease entered the study. The median number of courses per patient was four (range 1-14). One patient was not evaluable for response. There were three partial remissions [12%; 95% confidence interval (CI) 2.6% to 31.2%] and nine stable disease situations (36%; 95% CI 18.0% to 57.5%), while the tumours of 12 patients (48%; 95% CI 27.8% to 68.7%) showed progressive disease after three treatment cycles. WHO grade 3/4 toxicity was rare and symptomatic in only one patient, who experienced grade 4 diarrhoea and grade 3 nausea and vomiting. Symptomatic benefit was seen in 12 patients. Median survival was 185 days (95% CI 129-241) with six patients still alive. CONCLUSIONS: The efficacy of raltitrexed plus gemcitabine is limited, but compares well with other chemotherapy treatment options in advanced pancreatic cancer. However, this combination is convenient and symptomatic toxicity is rare. Thus, raltitrexed and gemcitabine should be investigated further in combination with drugs interfering with specific molecular targets.

Adenocarcinoma↗
PubMed2003

Adjuvant therapy in pancreatic cancer: historical and current perspectives.

The results from pancreatic ductal adenocarcinoma appear to be improving with increased resection rates and reduced postoperative mortality reported by specialist pancreatic cancer teams. Developments with medical oncological treatments have been difficult, however, due to the fundamentally aggressive biological nature of pancreatic cancer and its resistance to chemotherapy coupled with a relative dearth of randomised controlled trials. The European Study Group for Pancreatic Cancer (ESPAC)-1 trial recruited nearly 600 patients and is the largest trial in pancreatic cancer. The results demonstrated that the current best adjuvant treatment is chemotherapy using bolus 5-fluorouracil with folinic acid. The median survival of patients randomly assigned to chemoradiotherapy was 15.5 months and is comparable with many other studies, but the median survival in the chemotherapy arm was 19.7 months and is as good or superior to multimodality treatments including intra-operative radiotherapy, adjuvant chemoradiotherapy and neo-adjuvant therapies. The use of adjuvant 5-fluorouracil with folinic acid may be supplanted by gemcitabine but requires confirmation by ongoing clinical trials, notably ESPAC-3, which plans to recruit 990 patients from Europe, Canada and Australasia. Major trials such as ESPAC-1 and ESPAC-3 have set new standards for the development of adjuvant treatment and it is now clear that such treatment in this field has the potential to significantly improve both patient survival and quality of life after curative resection.

Carcinoma, Pancreatic Ductal↗
PubMed2003

Chronic pancreatitis: the perspective of pain generation by neuroimmune interaction.

Chronic pancreatitis (CP) is an inflammatory, often painful, disease of the exocrine pancreas which leads to exocrine insufficiency. The pathophysiology of pain in CP is incompletely understood. Several hypotheses have been advanced, including pancreatic and extrapancreatic causes. Here, the different pain hypotheses are discussed and evidence is presented that neuroimmune interactions are significant in the pathogenesis of pain generation and inflammation in CP. A better understanding of the complex cellular and molecular mechanisms of neuroimmune interactions should offer possibilities for innovative therapy and long term disease prevention.

Chronic Disease↗
PubMed2003

How Helicobacter Pylori changed the life of surgeons.

Helicobacter Pylori infection has been identified as a pathogenic factor in a number of gastroduodenal diseases, most importantly in gastric and duodenal ulcer disease. This association and the development of H. PYLORI eradication therapies has had a tremendous influence on the surgical therapy for these disorders. Decades ago, surgery was the therapy of choice for gastric and duodenal ulcers. Now, however, the first line of therapy includes treatment of H. PYLORI infection, suppression of gastric acid secretion, and protection of gastric mucosal barriers combined with a range of endoscopic procedures. These developments have had a major impact on the indications for surgery in benign gastroduodenal diseases. In addition, advances in our understanding of the pathogenetic mechanisms of H. PYLORI infection have also changed our views of gastric mucosa-associated lymphoid tissue lymphoma, gastric cancer, and gastroesophageal reflux disease.

Digestive System Surgical Procedures↗