The intermediate effect and the diagnostic accuracy in clinical case recall of students and experts in dental medicine.

INTRODUCTION: The extensive knowledge of experts facilitates the solving of domain-specific problems. In general, this is due to the fact that experts recall more detailed information than do novices or even advanced students. However, if physicians of different expertise levels are asked to write down the details of a given case, advanced medical students recall more information than experts. This phenomenon was called the 'intermediate effect' and is considered to be a specific feature of medical expertise. The aim of the here presented study was to examine this observation in the domain of dental medicine. MATERIALS AND METHODS: Sixty-one students and 20 specialised dentists participated in this study. Three clinical case descriptions were presented and afterwards the participants were told to write down all concrete information they remembered. Finally, they had to come up with a diagnosis. Interrater agreement, diagnostic accuracy and the recall explanation protocols were analysed statistically in comparison to state-of-the-art (canonical) explanations of the clinical cases. RESULTS: The mean interrater agreement was 96.2 +/- 3.37%. It was shown statistically that the more experienced the participants, the more accurate their diagnoses were (P < 0.001). The statistical analysis using the Games-Howell test demonstrated significant more written recall of the 5th-year students compared with 3rd- and 4th-year students and experts (P < 0.05). CONCLUSION: The results of this study suggest the existence of the intermediate effect in clinical case recall in dental medicine and thereby corroborate its importance and general applicability for different medical domains.

The role of pathophysiological explanations in clinical case representations of dental students and experts.

INTRODUCTION: Teaching of biomedical knowledge lays the foundations for the understanding and treatment of diseases. However, the representation of pathophysiological explanations in the management of clinical cases differs for various levels of medical expertise and different theories have been proposed to explain this phenomenon. The present study investigated for the first time how biomedical knowledge is used in clinical reasoning in dental medicine. MATERIALS AND METHODS: In an experimental study 20 experts in the field of Periodontology and 61 students of different levels of training produced written pathophysiological explanations after having studied three different clinical cases. By comparing the written protocols to a visualised expert-made 'canonical' explanation the concepts used in the pathophysiological explanation were counted and classified as well as the links between concepts. RESULTS: The statistical analysis by MANOVA showed significant differences between third- and fourth-year students, students of intermediate expertise level (fifth-year) and experts for various parameters qualifying concepts or links of the written pathophysiological explanations. The participants of intermediate expertise level produced a high rate of concepts and links; however, characteristic findings for knowledge encapsulation in the different levels of expertise were not evident. The analysis showed that the design of the clinical cases and of the canonical explanations significantly influenced the outcomes. CONCLUSION: The present study demonstrated the pathophysiological representations of clinical cases in dental students and experts to be different from other medical disciplines. It could be assumed that this observation is based on different contents for teaching of practical skills and diagnostic procedures in dental compared with medical education.

[Long-term survival of curatively operated gastric cancer: influence of the gender and splenectomy]. / Langzeitüberleben nach kurativer Magenkarzinomoperation: Bedeutung des Geschlechts und der Splenektomie.

BACKGROUND: Despite advances in operative technique long-term survival of curatively operated gastric cancer patients still remains poor with 5-year-survival of 25 %. Gender differences have been recognized in patients with colorectal carcinoma with a higher 5-year-survival of women. The long time-survival of the individual patient is closely dependent on his immunofunction. If a splenectomy has to be carried out, the postoperative immunofunction will be affected considerably. Thus, the question arises as to how far gender and splenectomy influence the long time-survival after curative gastric cancer surgery. METHODS: In a retrospective analysis of 505 patients with gastric cancer who had been treated between the years 1992 and 2002, a curative resection, i. e. R0, could be performed in 243 patients (48.1 %) with a definite classified tumour stadium according to the UICC (1997). The sociodemographic, operative, histomorphologic and postoperative data of each patient were collected, stratified by gender and compared using log-rank-test (survival) and chi-square-test (distribution). Multivariate analysis was performed by cox regression. The level of significance was set at p < 0.05. RESULTS: The sociodemographic, histopathologic and operative data between the two genders were comparable. The morbidity between men and women was not significant. However the rate of postoperative sepsis was higher in men (p < 0.05). With regard to the long-term survival, no difference could be shown between the two groups. However, splenectomy had a significant effect on long time-survival. Women with preserved spleen had a significantly improved five-year-survival rate as compared to women undergoing splencetomy and men with preserved spleen (p < 0.05). Multivariate analysis revealed only the tumour stage as a predictor for long time-survival in men, whereas in women the extend of lymphadenectomy and sepsis also influenced long time-survival. CONCLUSION: Long time-survival of curatively operated gastric cancer patients is gender dependent in terms of splenectomy. Therefore, gender differences should be taken into account in analysing long-term data of oncological patients.

Expression and distribution of prolactin receptor in normal, fibrotic, and cirrhotic human liver.

Liver cirrhosis is often associated with elevated levels of prolactin (PRL). This is commonly attributed to impaired hepatic metabolism of estrogens. However, there is evidence suggesting that PRL may be an important factor in hepatic tissue regeneration. To investigate the role of PRL in the pathogenesis of liver cirrhosis, we used RT-PCR and immunhistochemical staining to analyze changes in the expression and the histological distribution of the prolactin receptor (PRLR) in normal, fibrotic and cirrhotic hepatic tissue. Liver tissue was obtained from 29 surgically explanted human livers. The histological examination demonstrated normal liver tissue (n=9) as well as different grades of fibrosis (n=10) and cirrhosis (n=10). In liver cirrhosis and fibrosis, PRLR-mRNA was expressed at a higher level compared to normal liver specimens. Immunohistochemical staining of normal liver tissue demonstrated homogeneous distribution of the PRLR in the hepatocytes and in the epithelial cells of the bile ducts. This pattern of distribution was lost in fibrosis, where an accumulation of the PRLR was observed in the damaged hepatocytes. As no PRL-mRNA was detectable in normal, fibrotic or cirrhotic tissue, PRL does not act through autocrine or paracrine mechanisms. These data confirm previous results, which we obtained using an animal model for experimental liver cirrhosis in rats suggesting a metabolic function of PRL in normal liver and a regenerative function in fibrotic and cirrhotic liver. In conclusion, PRL might be involved in the pathogenesis of liver cirrhosis.

Intraoperative radiofrequency ablation (RFA) for irresectable liver malignancies.

AIMS: To evaluate the outcome of patients who received radiofrequency ablation (RFA) at open laparotomy in patients with irresectable liver malignancies. METHODS: Twenty-six consecutive patients who underwent explorative laparotomy and were found to be irresectable or who had been assessed not suitable for either resection or percutaneous RFA received intraoperative RFA. An expandable electrode (RITA Medical systems) was used. Follow-up comprised CT-scans in 6-12 week intervals. RESULTS: Patients' age ranged from 35 to 72 years (median 61). A variety of pathologies were treated. In 26 patients, 88 hepatic lesions were treated: 32 with resection and 56 with RFA. The mean diameter was 4.0+/-2.6 cm with a maximum of 10 cm. In 22 patients with hepatic metastases (18 colorectal, one leiomyosarcoma, one endometrium carcinoma, one renal cell carcinoma, one malignant phaeochromocytoma) 74 lesions (median 3.4 per patient) were treated (25 by resection, 49 by RFA). Eleven patients received simultaneous resection and RFA: resection of anatomical segments in six and atypical resection in seven patients. Procedure related complication rate was 19.2%. The mean follow-up was 14.6+/-9.2 months (2-36 months). Three patients developed recurrence at the site of previous RFA indicating incomplete ablation. The overall local control rate after one year was 92 and 90.9% for patients with colorectal liver metastases, respectively. Seventeen patients (65.4%) suffered from tumour progress. In 14 patients (53.9%) tumour occurred at new hepatic localisations and in five patients extrahepatic tumour relapse was diagnosed. Twelve patients have died so far (median survival 18 months, range 4-27). Nineteen patients had either completed a follow-up of at least 12 months or died within this period, resulting in an one year survival rate of 79% (80% for liver metastases). CONCLUSION: Intraoperative RFA is a valuable tool in liver surgery which extends the surgical spectrum in cases of irresectable malignancies.

[Modification of the liver resection technique with radiofrequency coagulation]. / Modifikation der Leberresektionstechnik durch Radiofrequenzkoagulation.

INTRODUCTION: Since the introduction of liver resection, intraoperative blood loss is considered to be a major risk factor for perioperative morbidity and mortality. Radiofrequency energy-an established technique for in situ ablation-was used to facilitate liver resection by creating a nearly bloodless tissue plane. METHODS: After thorough manual and sonographic exploration of the liver, the planned and marked resection plane was coagulated by radiofrequency and then transected. Seven patients with liver metastases of colorectal carcinoma were operated on employing this technique. RESULTS: A nearly bloodless transection of the parenchyma could be achieved in all cases. Only two patients received blood transfusions: one due to a low preoperative hemoglobin and one due to extended additional abdominal surgery. Procedure-related complications included one case of a second-degree burn to the thigh and one case of postoperative bile leakage requiring hemihepatectomy. CONCLUSIONS: Radiofrequency-assisted resection offers a valuable additional option in liver surgery, especially in patients with an increased risk of intraoperative bleeding (cirrhosis, coagulopathy).

[Short bowel ileus due to a stenotic ileocecal tumor of tuberculous origin]. / Dünndarmileus bei stenosierendem Ileozökaltumor und abdomineller Tuberkulose.

Abdominal tuberculosis is a rare disease. Therapy usually consists in drug treatment while surgery is only performed in complicated cases. We report on a 75 year-old man who presented with clinical and radiologic signs of bowel obstruction. The patient complained of weight loss and B-symptoms. There was a history of drug treatment for tuberculosis of the neck and throat in the medical department four weeks prior to admission. Intraoperatively a coecum stenosis was found due to a large tumor that macroscopically appeared with a diffuse carcinomatosis of the peritoneum. A right hemicolectomy was performed. Histopathology findings revealed a granulomatous inflammation with epithelioid cells. Signs of peritoneal carcinomatosis were not seen. The patient recovered well after an additional tuberculostatic treatment and was discharged after 14 days. At present he is free of symptoms. Even after tuberculostatic treatment lymphatic tuberculosis might show signs of progression that can lead to an abdominal presentation.

Pleiotrophin can be rate-limiting for pancreatic cancer cell growth.

Pancreatic cancer is one of the most aggressive malignant tumors, with an overall survival rate of 2%. The identification of growth factors that contribute to the malignant phenotype can help to identify new targets for therapy. In this study, we analyzed the growth factor pleiotrophin (PTN) that was originally described as a developmentally regulated cytokine during early embryogenesis. More recently, PTN was found to be overexpressed in a variety of neuroectodermal tumors and described as an essential angiogenic growth factor in choriocarcinoma and melanoma, promoting metastatic growth. Recently, we discovered high expression levels of PTN in patients with gastrointestinal malignancies, particularly in those patients with pancreatic cancer. However, it is not known whether PTN is a contributor to the growth of pancreatic cancer or is only a bystander. We used ribozymes to deplete PTN mRNA from Colo357 pancreatic cancer cells and studied the resulting phenotype. The reduction of PTN resulted in a decrease in the proliferation rate, soft agar colony formation, and tumor growth in animals. Supplementation of cells with PTN partially reversed the ribozyme effect. The autocrine function of PTN was confirmed by using PTN-binding antibodies that inhibited the proliferation rate by 50% in Colo357 cells but also in a different pancreatic cancer cell line, Panc89. Our study identifies PTN as a new and essential growth factor for pancreatic cancer. Due to the restricted expression pattern of PTN in adults, PTN is suggested as a target for pancreatic cancer therapy.

Immunocytological detection of isolated tumour cells in the bone marrow of malignant melanoma patients: a new method for the detection of minimal residual disease.

AIMS: Immunocytologically detected isolated tumour cells indicate a poor prognosis. This has been shown in breast, gastrointestinal and lung cancer, and might thereby help to indicate adjuvant therapy. Immunocytology has been proved to be a reliable technique and enables a phenotypic tumour cell characterization. We find this technique superior to molecular biological techniques such as reverse transcriptase polymerase chain reaction RT-PCR. So far, immunocytological studies have not been performed in malignant melanoma patients and our study aimed to establish this approach in melanoma patients. METHODS: Twenty melanoma patients who underwent surgery for lymph-node metastasis using a radical lymphadenectomy were studied. Using the immunoperoxidase method, cytospins of bone marrow aspirates (1.5x10(6)cells per patient) were stained with the monoclonal antibody HMB-45. Nineteen patients who were surgically treated but did not suffer from malignant melanoma were included as a control group. RESULTS: Four of the 20 patients showed isolated tumour cells in the aspirate. Three of these patients had stage IV disease. One patient had a stage III tumour (1/7; 14.3%). One patient was classified as stage II and did not show tumour cells in the bone marrow. No staining cells were found in the control group (n=19). CONCLUSIONS: Our study demonstrates that the immunocytological approach can be used as a new technique to detect occult tumour cell dissemination in malignant melanoma patients and supports previous findings in carcinoma of the stomach, colon, pancreas and other tumours.

Limited sensitivity of iodine-123-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl ] benzamide whole-body scintigraphy in patients with malignant melanoma: a comparison with thallium-201 imaging.

The aim of this prospective study was to assess the diagnostic value of iodine-123-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide (IBZM) whole-body imaging in comparison to thallium-201 scintigraphy in patients with metastatic malignant melanoma. Ten patients with suspected or proven locoregional metastases of malignant melanoma underwent whole-body scintigraphy both with 201Tl and 123I-IBZM prior to scheduled surgery. Whole-body scans and planar scintigrams were acquired at 5 min and 30 min after injection of 100 MBq 201Tl and at 10 min, 2 h, 4 h and 24 h after injection of 185 MBq 123I-IBZM. Ten out of 12 melanoma metastases, both melanotic and amelanotic as proven histologically, were detected by 201Tl with a sensitivity of 83%. 123I-IBZM showed tracer uptake only in 3 melanotic metastases (sensitivity: 25%) with a maximum tumor-to-background ratio within 4 h, while none of the amelanotic metastases was IBZM-positive. All lesions localized by 123I-IBZM showed tracer uptake of 201Tl as well, while 201Tl-negative lesions were also negative with IBZM. Because of the poor results of IBZM, the study was terminated after an interim evaluation of 10 patients. 123I-IBZM is a tracer with only moderate sensitivity in melanotic melanoma lesions, suggesting that this method has no clinical value as a routine investigation in melanoma patients. In comparison, our previous results with 201Tl whole-body scintigraphy yielded a significantly higher sensitivity of about 80% in patients with locoregional melanoma metastases and may thus offer considerable potential in non-PET melanoma imaging.

Relationship between serum concentrations of the growth factor pleiotrophin and pleiotrophin-positive tumors.

BACKGROUND: Growth factors produced by tumor cells are essential for tumor expansion and may be useful in monitoring tumor progression or therapeutic efficacy if the factors are released into the circulation. In this study, we measured serum levels of pleiotrophin, a secreted heparin-binding growth and angiogenesis factor, in mice bearing human tumor xenografts to determine whether these levels reflected overall tumor burden, and we examined the relationship between tumor expression of pleiotrophin and serum levels of this factor in patients with cancer. METHODS: Pleiotrophin in serum from mice and humans was measured by use of a highly sensitive enzyme-linked immunosorbent assay. For the clinical studies, serum specimens were obtained from 193 patients with various cancers of the gastrointestinal tract and from 28 healthy control subjects. In a subset of 64 cancer patients, serum levels of pleiotrophin were measured at the time of surgery, and tumor expression of this factor was detected immunohistochemically. All P values are two-sided. RESULTS: In mice, serum pleiotrophin levels were found to increase as a function of tumor size. In humans, elevated serum pleiotrophin levels were found in patients with pancreatic cancer (n = 41; P<.0001) and colon cancer (n = 65; P = .0079) but not in patients with stomach cancer (n = 87; P =.42). A statistically significant positive association was found between elevated levels of pleiotrophin in serum drawn at the time of surgery and expression of this factor by tumors (P<.0001). In both mice and humans, serum pleiotrophin levels dropped after successful tumor removal. CONCLUSIONS: Elevated serum pleiotrophin levels can indicate the presence of tumors expressing this factor. Monitoring serum levels of pleiotrophin may prove useful in determining the pharmacologic efficacy of cytotoxic or anti-pleiotrophin therapy.

[Primary varices of the colon. A rare cause of gastrointestinal bleeding]. / Primäre Varikosis des Kolons. Eine seltene Ursache der gastrointestinalen Blutung.

HISTORY: A 34-year-old patient presented with a two-day history of passing bright-red blood with his stools. There was no contributory past or family history and he had no accompanying symptoms. INVESTIGATIONS: Colonoscopy revealed many varices in the colon and terminal ileum without an active source of bleeding. Angiography failed to demonstrate any bleeding or vascular anomaly in the splanchnic region. Abdominal ultrasound and gastroscopy as well as biochemical tests did not indicate portal hypertension or liver cirrhosis. TREATMENT AND COURSE: On the night of admission there was a renewed fall in haemoglobin concentration. Emergency colonoscopy again failed to discover a source of bleeding. After transfusion of four units of erythrocyte concentrate the further course was uneventful. 8 months and 3 years later there were further episodes of marked bleeding per rectum. At the latest admission no source for the bleeding was found but there was some blood oozing in the sigmoid colon. Biochemical tests were unremarkable. The large varices were again seen in the colon and terminal ileum. Gastroscopy, Doppler sonography of the liver and repeat abdominal sonography again failed to demonstrate portal vein thrombosis, liver cirrhosis or portal hypertension. CONCLUSION: In case of colonic varices the differential diagnosis should include portal hypertension with chronic liver disease, portal vein thrombosis, vascular anomalies or postoperative complications. The treatment of primary varices, which are rare, is conservative.

[Cystic liver, an indication for liver transplantation or decompressive resection?]. / Die Zystenleber, eine Indikation zur Lebertransplantation oder zur dekompressiven Resektion?

In patients suffering from polycystic liver disease sclerosing therapy, decompressive hepatic resection and liver transplantation represent the main therapeutic options. Since 1987, 10 females with highly symptomatic polycystic liver disease underwent hepatic resection for decompression (five left lateral bisegmentectomies, one left hemihepatectomy, one right central and three bilateral atypical resections). Despite of a 0% lethality 3 patients developed complications, in two cases an abscess had to be drained and in one case a postoperatively increasing hepatic insufficiency required urgent liver transplantation. Patient's symptoms were remarkably improved in 8 cases, but only 6 patients had a long lasting benefit over years. One patient was resected a second time three years after the first operation and is free of symptoms for another five years. 6/96 the "European Liver Transplant Registry" has listed 81 patients after liver transplantation because of polycystic liver disease. 5-year survival is 78.2%. So liver transplantation offers a therapeutic alternative for patients severely suffering from symptoms or increasing hepatic insufficiency.

201Tl whole-body scintigraphy in patients with malignant melanoma.

The aim of this study was to evaluate 201Tl whole-body imaging in the detection of metastases prior to surgery in patients with malignant melanoma. Whole-body imaging was performed in 30 patients with known or suspected metastases 5 and 30 min after administration of 150 MBq 201Tl. The imaging results were compared with the histopathological findings in each patient on a lesion-by-lesion basis. Of the 39 metastases proven histopathologically, 34 were detected by 201Tl imaging (sensitivity = 87%), including 4 in-transit metastases and one inguinal lymph node metastasis which were unknown prior to investigation. Due to these additional findings on 201Tl imaging, scheduled surgical therapy was changed in three patients. 201Tl imaging was false-negative in four lymph node metastases and one skin lesion, and there were two false-positive 201Tl scans with tracer accumulation in inflammatory sites. The mean target-to-background ratio on the true-positive scans was 1.72 +/- 0.37 and 1.67 +/- 0.41 (P > 0.05) at 5 and 30 min post-injection respectively. In conclusion, 201Tl whole-body imaging appears sensitive and simple to perform in the detection of metastases prior to surgery in melanoma patients.

[Cushing syndrome with life-threatening infectious complications]. / Cushing-Syndrom mit lebensbedrohlichen infektiologischen Komplikationen.

HISTORY AND ADMISSION FINDINGS: During treatment of phlegmon of the face, which involved the cornea, a 54-year-old man was transferred to the medical ward because of dyspnoea of rapid onset. He was known to have arterial hypertension with heart failure and diabetes mellitus, and to have sustained a fracture of the femur after minimal trauma. He had central cyanosis, ankle oedema, cushingoid appearance and ecchymoses. Loud rales ware heard over both lungs. Body temperature was 38.9 degrees C. INVESTIGATIONS: Laboratory tests indicated acute inflammation and he had signs of global respiratory failure. X-ray of the thorax showed cardiomegaly and an infiltrate in the right lung. The ECG indicated an old myocardial infarct and left heart strain. TREATMENT AND COURSE: Mechanical ventilation with intubation became necessary because of deteriorating respiratory function. Broad-spectrum antibiotics and antibiotics against suspected fungal pneumonia were administered; he was extubated after 28 days. Cortisol excretion of more than 3300 micrograms/24 h and failure of cortisol suppression after 1 mg dexamethasone were diagnostic of hypercortisolism. Other endocrine tests revealed an adrenal lesion, shown by computed tomography to be an adrenal tumour, 3 cm in diameter. It was excised and histologically proved to be an adenoma. INTERPRETATION: Nowadays infectious complications due to cortisol-associated immunosuppression are rare in Cushing disease, because of its early recognition and treatment. But hypercortisolism should be considered in patients with severe and prolonged infections.

Human galanin modulates human colonic motility in vitro. Characterization of structural requirements.

BACKGROUND: Human galanin (hGal) is a 30-residue non-amidated gut-brain peptide that shows considerable sequence divergence compared with galanin (Gal) forms of other species. Conflicting results have been reported with regard to the structural requirements for its modulatory action on gut motility. METHODS: We investigated the effect of human and rat Gal and substituted analogues of Gal on the contractility of longitudinal muscle strips of the human colon in vitro. RESULTS: Both hGal and rGal contracted the preparations in a concentration-dependent and tetrodotoxin-resistant manner without difference in sensitivity. The NH2-terminally truncated peptides hGal (3-30) and rGal (3-29) were inactive, whereas the NH2-terminal fragments, hGal (1-21) and rGal (1-18), remained fully responsive. Single amino acid substitutions at NH2-terminal positions showed divergent results: substitution of Trp2 reduced significantly potency and efficacy, whereas substitutions at positions 1, 3, 4, or 5 did not markedly modify the bioactivity of Gal. Galantide, a high-affinity Gal antagonist in the central nervous system, is a full agonist in human colonic smooth muscle. CONCLUSION: The COOH-terminal part of Gal contributes mainly the receptor-binding affinity of the peptide, whereas the NH2-terminal region is essential for biologic activity.

Non-parasitic liver cysts and polycystic liver disease: results of surgical treatment.

The results of surgical treatment in 8 patients with polycystic liver disease (group A) and 6 patients with symptomatic simple cysts (group B) are presented. In group A, all patients underwent hepatic resection, in some cases combined with deroofing or fenestration procedures. Complications occurred postoperatively in 3 patients (37.5%). Two of these three patients had no perceived benefit from the surgical treatment. Two other patients had recurrent symptoms 12 and 20 months after operation, and one patient underwent a second resection after a 5-year-interval; she is now symptom-free after 19 months of follow-up. In group B, no complications occurred after surgical treatment consisting of either deroofing or pericystectomy. These patients were symptom-free after 5-32 months of follow-up. The therapeutic management of non-parasitic cystic liver disease is still under discussion. We advocate wide deroofing or pericystectomy for symptomatic simple cysts. Hepatic resection in highly symptomatic polycystic disease is surgically demanding and should be performed by an experienced liver surgeon. Relief of symptoms can be achieved, but the rate of complications is relatively high.

[Sarcoma of the gastrointestinal tract]. / Sarkome des Gastrointestinaltraktes.

From 1970-1988 15 patients were operated on gastrointestinal sarcomas. Four more patients with this diagnosis had to be excluded after histological reclassification. A resection with curative intention was possible in 10 cases. Three patients initially had distant metastases, in 6 patients they appeared postoperatively. Regarding prognosis the TNMG-system proved to be useful only concerning lymph nodes. Eight patients died because of tumor progression, four have no evidence of disease 20-97 months postoperatively. One patient with liver metastases has a complete remission 32 months after chemotherapy. We found a 5-year-survival rate of 28%. Radical tumor resection and lymphadenectomy is recommended, distant metastases should be treated by chemotherapy.