[Overview on research in the field of medical education]. / Übersicht über die Forschung im Bereich der medizinischen Ausbildung.

Medical education is a relatively young field of research that has been characterized by many innovations over the last 20 years. The main topics were the preparation of students for their medical work and imparting of profound knowledge about scientific contexts in medicine. For a long time, the main focus was on learning the necessary knowledge and skills; however, this is no longer considered sufficient. In order to carry out the work as a physician well, other qualities are also necessary, such as communication, collaboration, professionalism, science and reflectivity. Worldwide these aspects are being increasingly integrated into the learning objectives of medical schools and residency programs. The structure of medical studies at many universities has also changed. So-called vertical integration strengthens the integration of theoretical preclinical training and the clinical phase. This means that in the preclinical phase training is more practice-oriented and in the clinical phase a more structured form of training takes place. In the first years of study, students are prepared for the clinical phase by discussing patient cases and practicing skills in simulation centers. In addition, the clinical working environment is increasingly used as a learning environment. Developments have also been made regarding examinations: in addition to knowledge and skills, students and residents are now also assessed regarding performance in practice. Using more realistic assessments, e.g., Objective Structured Clinical Examinations and Workplace-based Assessments, students are evaluated more on their actual performance in practice. By means of the Entrustable Professional Activities method, students are gradually given more responsibility in order to prepare them for their future tasks.

[Curriculum for Practical Surgical Education during Internships - with a Strategy for New Perspectives]. / Curriculum der chirurgisch-praktischen Ausbildung im PJ - mit Strategie zu neuen Perspektiven.

BACKGROUND: It seems that the experience gained in the courses of surgical training in medical education does not really motivate students for surgery in Germany. Inspired by this problem the Department of Surgery of the Klinikum rechts der Isar, Technical University of Munich has developed a substantial reform for the internship since 2009 with the aim of not only improving the quality of education significantly, but also the attractiveness and thus the fascination for the subject. METHODS: Based on the slogan "We want to awaken your fascination for surgery" a structured and standardised training of all students in their internship regardless of the ward or section and local conditions was developed. For this purpose a completely new curriculum was steadily implemented into clinical practice, based on the following four basic principles: (i) integration and perception in the clinic, (ii) central and peripheral maintenance, (iii) systematic and individual training, (iv) evaluation and feedback at all levels. To analyse the effectiveness of the reform, standardised evaluations by students and faculty were carried out regularly. RESULTS: To date, since the beginning of the reform in 2009, there has been an approximately linear increase in the number of students in the PJ surgery. The daily systematic courses showed a good to excellent rating in all formats. The comparison showed a clear increasing trend in all the values, in particular, the "integration into the overall hospital" significantly improved (mean, 4.7 vs. 5.5, p = 0.003). However, the point "motivating for surgery" (mean, 3.3) remains at a low level. But also medical educators were satisfied with the new curriculum for the internship students (mean, 4.5). CONCLUSION: The reform was adopted universally in a very positive manner and the current data support the need for such a reform. Overall, the reform showed a positive development of the internship training in the surgical department of the faculty. The satisfaction of the students and teachers could be increased by gradual implementation of the reform. Even if a lot of individual aspects gain a higher acceptance, the main concern, the inspiration of the "fascination" of the central surgical field, the training in the operating room, seems to succeed only partially.

Surgeon-patient communication in oncology.

Little is known about the quality of post-operative communications following oncological surgery and the satisfaction of patients with the communication process. Thirty-eight patients who underwent surgery for primary gastrointestinal cancer were interviewed before being discharged from the hospital. The patients' recall of information concerning the surgery, histological diagnosis, post-operative therapy and treatment goal was assessed. The congruence between the information provided by the surgeons and that retained by the patients was evaluated. The information provided by the surgeons about the diagnosis, histology and post-operative therapy plan was correctly recalled by over 92%, 81% and 97% of the patients respectively. Only 70% of the patients correctly recalled information about the goal of the treatment. Moreover, patients receiving only palliative treatment showed less recall of information about the treatment goal than patients receiving curative treatment (33% versus 89%). The surgeons reported that only 35% of the patients left the hospital completely informed. Overall, the patients were highly satisfied with their communication with their surgeon, and the patients' recall of information was generally good. The information given by the surgeons was often incomplete, however. Our explorative analysis showed that the quality of communication was often worse for patients with a palliative treatment goal than for patients with a curative treatment goal.

[Modular postgraduate training in surgery - a national concept with future]. / Modulare Weiterbildung in der Chirurgie - ein nationales Konzept mit Zukunft.

BACKGROUND: The quality of postgraduate training is an important motivating factor for the career decisions of young doctors and has an impact on the satisfaction of postgraduate trainees. In Germany, we still lack a postgraduate training programme in surgery that defines the competency profile at the time of certification. This article describes the development of a national modular competency-based core curriculum for postgraduate surgery training as well as first experience and evaluation data from the initial period of implementation. METHODS: The curriculum was developed in a group of highly motivated surgeons according to the "Kern-cycle", a conceptual framework for curriculum development in medicine, and includs considerations from the "CanMEDS"-competency framework for physicians. The curriculum follows a "blended learning" concept with modular attendance courses and associated preparatory online courses. The didactics follows the principles of adult learning and are characterised by learner-centred, self-directed learning processes in small groups with feedback. The initial implementation phase was accompanied by a detailed evaluation of the general concept as well as the quality of content and didactics of the attendance courses. RESULTS: Seven of the planned 12 attendance courses have been designed, 6 courses have been implemented2q1. Altogether 562 participants from hospitals of all levels of patient care took part in the attendance courses, some of them in several courses. The gender distribution was almost balanced with a slight female surplus. The majority of participants were supported by their clinics through exemption from clinical work or financial sponsoring. 80 % of the participants completed the evaluation of the attendance courses. The data show a high degree of participant satisfaction with the content and didactic concept of the courses, as well as with the surrounding conditions and the commitment of the trainers. CONCLUSIONS: The evaluation data on the attendance courses implemented reveal a high acceptance among participants concerning the overall concept of the modular postgraduate training programme as well as the support of the programme by surgeons responsible for postgraduate training.

Implementing Kolb´s Experiential Learning Cycle by Linking Real Experience, Case-Based Discussion and Simulation.

BACKGROUND: Background: To prepare medical students for their future, they must become acquainted with clinical practice, for example by means of simulations, clerkships and discussing patient cases. By connecting these different approaches, according to Kolb´s experiential learning cycle, the learning effect can be strengthened. Methodology: In the development of a didactical program for students who are being prepared for their role as general practitioners, we have adopted a new didactic approach, in which educational formats are interlinked, according to Kolb´s experiential learning cycle. The content of these courses is determined by the Entrustable Professional Activities (EPAs) for the clerkship in family medicine, combined with the most common chief complaints of patients in the GP's practice. In 2019, the first course was implemented at the Technical University of Munich, Germany, with 6 medical students. A first seminar discusses patients who the students have seen for themselves during their clerkship in family medicine. In addition, matching theory is discussed and skills are practiced. In the next seminar, students apply the acquired knowledge and skills in scenarios with standardized patients. Students evaluated the courses as positive. The evaluations show they find discussing personally experienced patient cases and the opportunity to practice very valuable. Conclusions: A course design according to Kolb's Experiential learning cycle, which integrates experience, theory and simulation, is a valuable addition to existing forms of teaching in medical education. Students appreciated both discussing personally experienced patient cases and the opportunity to re-practice similar cases in a simulated environment. To gain more insight into the learning effects, it is recommended to further explore this approach in a different context.

Medical students' knowledge and attitudes regarding vaccination against measles, influenza and HPV. An international multicenter study.

INTRODUCTION: Inaccurate information leads to increased scepticism concerning vaccinations among health care workers. Therefore, a proper education of medical students on vaccination is important. METHODS: During summer term 2015, we performed a paper-based survey to identify the knowledge and attitudes of medical students on vaccinations against measles, influenza and HPV in seven medical schools in Germany, Austria and Switzerland. RESULTS: Altogether, 3,652 questionnaires were analyzed. Knowledge of country-specific public recommendations increased significantly with the number of semesters of medical studies. Concerning the knowledge about vaccinations against measles, influenza and HPV, one third of the answers were given correctly. Again, a strong correlation between the knowledge and the semester of medical studies could be observed. The attitudes concerning vaccinations in general and especially for HCWs were highly positive. CONCLUSIONS: This study provides some important arguments for the development of a comprehensive vaccination education for medical students.

Fast track--different implications in pancreatic surgery.

Concepts in "fast-track" surgery, which provide optimal perioperative care, have been proven to significantly reduce complication rates and decrease hospital stay. This study explores whether fast-track concepts can also be safely applied and improve the outcomes of major pancreatic resections. Perioperative data from 255 consecutive patients, who underwent pancreatic resection by means of fast-track surgery in a high-volume medical center, were analyzed using univariate and multivariate models. Of the 255 patients, 180 received a pancreatic head resection and 51 received distal, 15 received total, and 9 received segmental pancreatectomies. The patients were discharged on median day 10 with a 30-day readmission rate of 3.5%. The in-hospital mortality was 2%, whereas medical and surgical morbidities were 17 and 25%, respectively. Fast-track parameters, such as first stools, normal food, complete mobilization, and return to normal ward, correlated significantly with early discharge (p < 0.05). Patients' age, operation time, and early extubation proved to be independent factors of early discharge, shown through multivariate analysis (odds ratio: 4.0, 2.0, and 2.8, respectively; p < 0.05). Low readmission, mortality, and morbidity rates demonstrate that fast-track surgery is in fact feasible and safe and promotes earlier discharge without compromising patient outcomes.

How to assess communication skills? Development of the rating scale ComOn Check.

BACKGROUND: Good communication is a core competency for all physicians. Thus, medical students require adequate preparation in communication skills. For research purposes, as well as for evaluation in teaching, there is a clear need for reliable assessment tools. We analyzed the shortcomings of existing instruments and saw a need for a new rating scale. The aim of this publication is to describe the development process for, and evaluation of, a new rating scale. METHODS: First, we developed the rating scale in 10 steps. Then, two raters evaluated the newly developed rating scale by rating 135 videotaped consultations of medical students with standardized patients. Additionally, standardized patients evaluated students' performance, which was used as an outside criterion to validate ratings. RESULTS: Our rating scale comprises six domains with 13 specific items evaluated on a five-point Likert scale: initiating conversation, patient's perception, structure of conversation, patient's emotions, end of conversation, and general communication skills. Item-total correlation coefficients between the checklist items ranged from 0.15 to 0.78. Subscale consistency was calculated for domains comprised of more than one item and Cronbach's α ≥ 0.77, indicating acceptable consistency. Standardized patients' global evaluation correlated moderately with overall expert ratings (Spearman's ρ = .40, p < .001). CONCLUSION: Our rating scale is a reliable and applicable assessment tool. The rating scale focuses on the evaluation of general communication skills and can be applied in research as well as in evaluations, such as objective structured clinical examinations (OSCE). ABBREVIATIONS: CST: Communication skills training; ICC: Intra-class correlation coefficient; OSCE: Objective structured clinical examination; SP: Standardized patients; SD: Standard deviation; M: Mean.

The ECM proteoglycan decorin links desmoplasia and inflammation in chronic pancreatitis.

BACKGROUND: Recurrent inflammation in chronic pancreatitis (CP) is not well understood. AIMS: To investigate whether decorin, an extracellular matrix (ECM) proteoglycan with macrophage modulating activity, is a pathogenic factor allowing diseased pancreatic stroma to sustain inflammation by affecting the cytokine profile of accumulating inflammatory cells. METHODS: Decorin was examined in 18 donors and 32 patients with CP by quantitative reverse transcription polymerase chain reaction (QRT-PCR), western blotting, and immunohistochemistry of pancreatic specimens. QRT-PCR was used to assess cytokine expression in donor peripheral blood mononuclear cells (PBMC), exposed or not to decorin in vitro, and to compare it with the cytokine profile of circulating and resident mononuclear cells (MNC) of patients with CP. RESULTS: In CP, desmoplasia is associated with overexpression of decorin in the growing ECM and enlarged pancreatic nerves. In culture, exposure of MNC to decorin stimulated expression of the MNC recruiting chemokine MCP-1. In biopsies, MNC infiltrates in decorin rich CP tissue showed a 300-fold upregulation of MCP-1 compared with decorin free peripheral blood, whereas no difference was found in basal MCP-1 expression in PBMC of patients versus donors. This effect was specific for MCP1-other inflammatory cytokines, such as interleukin 1beta and tumour necrosis factor alpha, were not affected. CONCLUSION: Decorin is a molecular marker of desmoplasia in CP, and excessive decorin may allow fibrotic masses to nourish and protract inflammation by deregulating the process of MNC accumulation and activation. These data provide a molecular basis for surgical resection of diseased tissue as a treatment option in CP.

KAI1 is unchanged in metastatic and nonmetastatic esophageal and gastric cancers.

Down-regulation of KAI1 mRNA expression has been shown to be associated with the formation of metastases or disease progression in pancreatic cancer. Whether KAI1 possesses similar characteristics in other malignancies of the gastrointestinal tract is not known. Here, we compared the patterns of KAI1 mRNA expression in 41 esophageal cancers and 35 stomach cancers to assess whether KAI1 might also be of biological relevance in the metastatic ability of these tumors. By Northern blot analysis, KAI1 mRNA levels ranged widely in both normal and cancerous esophageal and gastric tissue samples, with no statistical differences. No association between KAI1 mRNA expression and tumor stage or tumor differentiation was seen in these tumors. In addition, KAI1 mRNA expression was similar in primary esophageal and gastric cancer samples with or without metastases. By in situ hybridization, KAI1 mRNA expression was evident in the cytoplasm of most squamous epithelial cells in the normal esophagus and in nonmucosal epithelial cells of the normal stomach. The staining intensity in the esophageal and gastric cancer cells was similar to that in the normal controls. This differential pattern of KAI1 mRNA expression in esophageal and gastric cancers in comparison to pancreatic cancer indicates that KAI1 seems to influence the potential of gastrointestinal cancer cells to metastasize differently. In esophageal and gastric cancers, the formation of metastases is not dependent on the reduction of KAI1 in the cancer cells.

Improved self- and external assessment of the clinical abilities of medical students through structured improvement measures in an internal medicine bedside course.

BACKGROUND: Bedside courses are of outstanding importance when training medical students. The fact that less and less teaching is taking place nowadays at the patient's bedside makes it all the more important that the available time be put to effective use. The aim of this study was to check whether structured improvement measures in the course (scripts, lecturer briefing, e-learning cases) would improve the abilities of the students on the basis of a subjective self-assessment as well as an external assessment by the lecturers with respect to clinical abilities. METHODS: Bedside teaching takes place in the fourth study year in the Medical Clinics of the TU Munich. Both students and lecturers had the chance to hand in an anonymous, quantitative self- and external assessment of the clinical abilities of the students (German grading system) after every course date. This assessment took place online in the three categories "Medical history & examination", "Diagnosis" and "Therapy". An overall period of four semesters, each with 6 course dates, was investigated. After two of the total of four semesters in the study, the course was changed by introducing scripts, lecturer briefing as well as interactive e-learning cases. The self- and external assessment was compared both within the semester (date 1-3: A; date 4-6: B), during the course as well as before and after introducing the improvement measures ("before" (T0): SS 2012, SS 2013, "after" (T1): WS 2013/2014, SS 2014). RESULTS: There was a significant improvement in one's own abilities on the basis of the self-assessment within each semester when comparing the first (A) and the last (B) course dates. Moreover, there was a significant improvement in the performances in all three categories when T0 was compared with T1, from both the point of view of the students ("Medical history & examination": T0 =2.5±0.9, T1=2.2±0.7, pp<0.001; "Diagnosis" T0=3.1±1.0, T1=2.8 ±0.9, pp<0.001; "Therapy": T0=3.8±1.3, T1=3.5±1.2, pp<0.018) and in two of the three categories from the point of view of the lecturers ("Diagnosis": T0=3.0±1.0, T1=2.7±0.7, p.=0.028; "Therapy": T0=3.8±1.1, T1=3.1±1.0, p<0.001). SUMMARY: The structured measures to improve the course including the interactive e-learning cases could have contributed to improved practical abilities with respect to the medical history and examination techniques as well as diagnostic and therapeutic thinking. The external evaluation by lecturers confirmed the improvement with respect to the diagnostic and therapeutic abilities. They only saw no dynamic change in the student's taking histories and clinical examinations.

Heavy chain ferritin acts as an antiapoptotic gene that protects livers from ischemia reperfusion injury.

Heme oxygenase-1 (HO-1) is induced under a variety of pro-oxidant conditions such as those associated with ischemia-reperfusion injury (IRI) of transplanted organs. HO-1 cleaves the heme porphyrin ring releasing Fe2+, which induces the expression of the Fe2+ sequestering protein ferritin. By limiting the ability of Fe2+ to participate in the generation of free radicals through the Fenton reaction, ferritin acts as an anti-oxidant. We have previously shown that HO-1 protects transplanted organs from IRI. We have linked this protective effect with the anti-apoptotic action of HO-1. Whether the iron-binding properties of ferritin contributed to the protective effect of HO-1 was not clear. We now report that recombinant adenovirus mediated overexpression of the ferritin heavy chain (H-ferritin) gene protects rat livers from IRI and prevents hepatocellular damage upon transplantation into syngeneic recipients. The protective effect of H-ferritin is associated with the inhibition of endothelial cell and hepatocyte apoptosis in vivo. H-ferritin protects cultured endothelial cells from apoptosis induced by a variety of stimuli. These findings unveil the anti-apoptotic function of H-ferritin and suggest that H-ferritin can be used in a therapeutic manner to prevent liver IRI and thus maximize the organ donor pool used for transplantation.

Pancreatic cancer: the potential clinical relevance of alterations in growth factors and their receptors.

Molecular alterations play a key role in the pathogenesis of gastrointestinal cancers. In the present paper we describe relevant molecular alterations in human pancreatic adenocarcinomas. Overexpression of growth factor receptors (EGF receptor, c-erbB2, c-erbB3, TGF beta receptor I-III), growth factors (EGF, TGF alpha, TGF beta-1-3, aFGF, bFGF), adhesion molecules (ICAM-1, ELAM-1) and gene mutations (p53, K-ras, DCC, APC) are present in a significant number of these tumors. These changes stimulate tumor growth and enhance the metastatic behavior of pancreatic cancer cells and thereby may contribute to shorter postoperative survival following tumor resection.

Comparative analysis of galectins in primary tumors and tumor metastasis in human pancreatic cancer.

Galectins are galactoside-binding proteins that exhibit an important function in tumor progression by promoting cancer cell invasion and metastasis formation. Using Northern blotting and Western blotting analysis, in situ hybridization (ISH), and immunohistochemistry (IHC), we studied galectin-1 and galectin-3 in tissue samples of 33 primary pancreatic cancers and in tumor metastases in comparison to 28 normal pancreases. Furthermore, the molecular findings were correlated with the clinical and histopathological parameters of the patients. Northern blotting and Western blotting analysis showed significantly higher galectin-1 and galectin-3 mRNA and protein levels in pancreatic cancer samples than in normal controls. For galectin-1, no ISH signals and immunoreactivity were observed in acinar or ductal cells in the normal pancreas and in pancreatic cancer cells, whereas fibroblasts and extracellular matrix cells around the cancer mass exhibited strong mRNA signals and immunoreactivity. Galectin-3 mRNA signals and immunoreactivity were strongly present in most pancreatic cancer cells, whereas in the normal controls only faint ISH and IHC signals were seen in some ductal cells. Metastatic pancreatic cancer cells exhibited moderate to strong galectin-3 immunoreactivity but were negative for galectin-1. No relationship between the galectin-1 and galectin-3 mRNA levels and the tumor stage or between the IHC staining score and the tumor stage was found. However, galectin-1 mRNA levels and the IHC staining score were significantly higher in poorly differentiated tumors compared with well/moderately differentiated tumors, whereas for galectin 3 no differences were found. The expression pattern of galectin-1 and galectin-3 in pancreatic cancer tissues indicates that galectin-1 plays a role in the desmoplastic reaction that occurrs around pancreatic cancer cells, whereas galectin-3 appears to be involved in cancer cell proliferation. High levels of galectin-3 in metastatic cancer cells suggest an impact on metastasis formation.

RUNX3 expression in primary and metastatic pancreatic cancer.

AIM: Runx transcription factors are important regulators of lineage specific gene expression, cell proliferation, and differentiation. Runx3 expression is lost in a high proportion of gastric cancers, suggesting a tumour suppressive role in this malignancy. This study investigates the expression and localisation of Runx3 in pancreatic tissues. METHODS: Quantitative polymerase chain reaction was used to measure Runx3 mRNA. Immunohistochemistry was carried out to localise Runx3 in normal pancreatic tissues, and in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Basal and transforming growth factor beta1 (TGFbeta1) induced Runx3 expression was analysed in cultured pancreatic cancer cell lines. RESULTS: Runx3 expression was low to absent in normal pancreatic tissues, but increased in a third of cancer tissues. Runx3 was present only in islets in normal pancreas, whereas in pancreatic cancers, Runx3 was detected in the cancer cells of seven of 24 samples analysed. In addition, it was expressed by lymphocytes in six of the 16 cases with lymphocyte infiltration. In pancreatic cancer cell lines, Runx3 mRNA was present in Colo-357 and T3M4 cells, but was low to absent in the other cell lines tested. TGFbeta1 repressed Runx3 mRNA expressed in Colo-357 cells, and had no effect on Runx3 expression in the other pancreatic cancer cell lines. CONCLUSION: Runx3 expression is restricted to islets in the normal pancreas. In contrast, a considerable proportion of pancreatic tumours express Runx3, and its expression is localised in the tumour cells and in the infiltrating lymphocytes. Thus, Runx3 might play a role in the pathogenesis of PDAC.

Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma.

BACKGROUND: Transforming growth factor betas (TGF-betas) are multifunctional polypeptides that have been suggested to influence tumor growth. They mediate their functions via specific cell surface receptors (type I ALK5 and type II TGF-beta receptors). The aim of this study was to analyze the roles of the three TGF-betas and their signaling receptors in human hepatocellular carcinoma (HCC). METHODS: HCC tissue samples were obtained from 18 patients undergoing partial liver resection. Normal liver tissues from 7 females and 3 males served as controls. The tissues for histological analysis were fixed in Bouin's solution and paraffin embedded. For RNA analysis, freshly obtained tissue samples were snap frozen in liquid nitrogen and stored at -80 degrees C until used. Northern blot analysis was used in normal liver and HCC to examine the expression of TGF-beta1, -beta2, -beta3 and their receptors: type I ALK5 (TbetaR-I ALK5), type II (TbetaR-II), and type III (TbetaR-III). Immunohistochemistry was performed to localize the corresponding proteins. RESULTS: All three TGF-betas demonstrated a marked mRNA overexpression in HCC in comparison with normal controls, whereas the levels of all three TGF-beta receptors showed no significant changes. Intense TGF-beta1, TGF-beta2, and TGF-beta3 immunostaining was found in hepatocellular carcinoma cells and in the perineoplastic stroma with immunohistochemistry, whereas no or mild immunostaining was present in the normal liver. For TbetaR-I ALK5 and TbetaR-II, the immunostaining in both HCC and normal liver was mild to moderate, with a slightly higher intensity in the normal tissues. CONCLUSION: The upregulation of TGF-betas in HCC suggests an important role for these isoforms in hepatic carcinogenesis and tumor progression. Moreover, the localization of the immunoreactivity in both malignant hepatocytes and stromal cells suggests that TGF-betas act via autocrine and paracrine pathways in this neoplasm.

Transforming growth factor betas and their receptors in human liver cirrhosis.

BACKGROUND: Transforming growth factor betas (TGF-betas) are a group of homologous polypeptides that exert pleiotropic effects on various cell types and stimulate the formation of extracellular matrix and fibrosis. To evaluate whether TGF-beta isoforms (TGF-beta1, TGF-beta2 and TGF-beta3) and their receptors (types I-III) are also of importance in the pathophysiology of liver cirrhosis, we analysed their concomitant expression and localization in human liver cirrhosis. PATIENTS: Cirrhotic liver tissue samples were obtained from 17 patients (four women, 13 men) with a median age of 41 years (range 22-67). Normal liver tissues from ten patients (seven women, three men) with a median age of 55 years (range 45-75) served as controls. METHODS: The tissues were fixed in Bouin's solution and paraffin-embedded for histological analysis. For RNA analysis, freshly obtained tissue samples were snap-frozen in liquid nitrogen and stored at -80 degrees C until analysed. Northern blot analysis was used to examine the expression of TGF-beta1, beta2 and beta3 and their receptors, type I (TbetaR-I), type II (TbetaR-II) and type III (TbetaR-III). Immunohistochemistry was performed to determine the localization of the corresponding proteins in the normal and the cirrhotic liver. RESULTS: Northern blot analysis revealed enhanced expression (P < 0.05) of TGF-beta1 (twofold increase), TGF-beta2 (threefold increase) and TGF-beta3 (8.5-fold increase) and of TbetaR-II (threefold increase) mRNA in liver cirrhosis in comparison with normal controls. In contrast, TbetaR-I (ALK-5) and TbetaR-III mRNA expression showed no significant changes. No TGF-beta isoform immunoreactivity was present in hepatocytes in either normal livers or in liver cirrhosis. However, in liver cirrhosis, intense TGF-beta1 immunoreactivity was present in bile duct and ductular epithelial cells (including ductular proliferations) and in inflammatory cells. In a few sinusoidal lining cells, faint TGF-beta1 and moderate TGF-beta2 immunoreactivity was present. TGF-beta3 immunostaining was present in bile duct and ductular epithelial cells, in inflammatory cells and in fibroblast-like spindle cells in liver cirrhosis. For TbetaR-I and TbetaR-II, the immunoreactivity was localized in hepatocytes and biliary cells in normal and cirrhotic liver tissues, with higher intensity for TbetaR-II in the cirrhotic liver. CONCLUSION: Enhanced expression of all three TGF-bea isoforms and of TbetaR-II in liver cirrhosis suggests their involvement in this fibrotic disorder. The higher immunoreactivity of the three TGF-beta isoforms in the bile duct epithelial cells in cirrhotic tissues suggests a possible role of these cells in the pathogenesis of liver cirrhosis.

What should be the standard operation in chronic pancreatitis: Whipple or duodenum-preserving pancreatic head resection?

Surgical options in the treatment of chronic pancreatitis have undergone both development and controversial discussion in the past decades. Operations such as the classical and pylorus-preserving Whipple resections are more and more being replaced by operations such as the duodenum-preserving pancreatic head resection, which preserves extrapancreatic organs like the stomach, the duodenum and the extrapancreatic bile duct. The latter operation preserves a normal food passage and glucose metabolism after surgical intervention. In addition, the duodenum-preserving pancreatic head resection provides long-term pain relief and reduction in up to 90% of chronic pancreatitis patients, as well as a general improvement in quality of life. This article will summarize and compare the surgical options in the treatment of chronic pancreatitis and will provide arguments why the duodenum-preserving pancreatic head resection should replace the classical and the pylorus-preserving Whipple resections as the standard surgical procedure used to treat chronic pancreatitis-related complications.

[Surgical therapy in chronic pancreatitis]. / Chirurgische Therapie der chronischen Pankreatitis.

In patients with chronic pancreatitis, surgical treatment is required when conservative approaches are unsuccessful in treating symptoms and complications of the disease. The indications for surgery are 1) recurrent abdominal pain which does not respond to analgesics and 2) duodenal, common bile duct and/or main pancreatic duct obstruction or stenosis. In addition, obstruction of the retropancreatic vessels with subsequent portal hypertension is an indication to operate. Over the last decades the surgical standards in the treatment of chronic pancreatitis have changed. Due to disappointing long-term results, pancreatic left resection and drainage procedures of the main pancreatic duct are limited only to a small number of patients. In a number of patients with chronic pancreatitis, inflammatory enlargement of the pancreatic head causes complications which require surgical treatment. In the past, the classical Whipple resection has served as the standard operation in these patients. However, the classical Whipple resection was initially inaugurated for pancreatic head malignancies, and in addition to resection of the pancreatic head it includes resection of the complete duodenum, the extra hepatic bile system and 2/3 of the stomach. The Whipple procedure's disappointing long-term results and especially its disappointing quality of life have led to the development of newer organ-preserving procedures designed to treat complications caused by chronic pancreatitis. The pylorus-preserving Whipple resection is a modification of the classical Whipple resection which avoids the resection of the stomach. Since its initial publication by Watson in 1945 and Traverso and Longmire in 1978, pylorus preserving Whipple resection has been performed by many surgeons for the treatment of chronic pancreatitis. However, the high incidence of postoperative diabetes mellitus following this operation is a major drawback that has limited its use. The duodenum-preserving pancreatic head resection was developed to selectively remove the pancreatic head subtotally by preserving the body and tail of the pancreas as well as the pylorus, the duodenum, and the extrahepatic biliary tract. With this organ-preserving operation all the pancreatic head-related complications of chronic pancreatitis can be abolished without inducing diabetes mellitus. Excellent short- and long-term follow-up results prove the superiority of the duodenum-preserving pancreatic head resection over the classical and the pylorus-preserving Whipple resections in patients with chronic pancreatitis. Therefore, the duodenum-preserving pancreatic head resection should be adopted as a new standard operation in patients with chronic pancreatitis and pancreatic head-related complications.

[Prognosis in pancreatic carcinoma]. / Die Prognose des Pankreaskarzinoms.

Pancreatic cancer is one of the most frequent carcinomas of the human gastrointestinal tract. despite considerable progress in diagnosis, its prognosis has remained unchanged during the last years. Up to now, there is no possibility to screen patients for pancreatic carcinomas, and the symptoms of the disease are uncharacteristic and often misleading. Surgical treatment, with resection of the tumor is the only chance for cure, but for experienced pancreatic surgeons, an advanced tumor stage at the time of operation is a common finding. Large studies reveal the poor prognosis of the disease. Only 20-30% of all patients suffering from pancreatic cancer can be operated with curative intention. In 80-85% of all cases, the tumor has spread into peripancreatic lymph nodes. Thus, mean 5-years survival rates of 3 to 5% are commonly reported, and the median survival time after establishment of diagnosis is 4-6 months. Improvements in surgical technique and postoperative patient's care have led to an impressive decrease in the formerly considerable morbidity and mortality after pancreatic resection. If the tumor can be resected at an early stage and the regional lymph nodes are not involved, median 5-years survival rates of 20-40% are commonly reported. Further approaches include more radical surgical procedures with dissection of the entire peripancreatic region and resection of the upper abdominal blood vessels. Whether this new technique or a combination of operation, radiation and chemotherapy will improve the prognosis of the disease remains unclear. Large clinical trials are necessary to prove these assumptions.