Mechanisms of Metastasis in Colorectal Cancer and Metastatic Organotropism: Hematogenous versus Peritoneal Spread.

Metastasis is the major cause of death in patients with colorectal carcinoma (CRC). The most common sites of metastasis are the liver and the peritoneum. Peritoneal carcinomatosis is often considered the end stage of the disease after the tumor has spread to the liver. However, almost half of CRC patients with peritoneal carcinomatosis do not present with liver metastasis. This brings up the question of whether peritoneal spread can still be considered as the end stage of a metastasized CRC or whether it should just be interpreted as a site of metastasis alternative to the liver. This review tries to discuss this question and summarize the current status of literature on potential characteristics in tumor biology in the primary tumor, i.e., factors (transcription factors and direct and indirect E-cadherin repressors) and pathways (WNT, TGF-ß, and RAS) modulating EMT, regulation of EMT on a posttranscriptional and posttranslational level (miRNAs), and angiogenesis. In addition to tumor-specific characteristics, factors in the tumor microenvironment, immunological markers, ways of transport of tumor cells, and adhesion molecules appear to differ between hematogenous and peritoneal spread. Factors such as integrins and exosomal integrins, cancer stem cell phenotype, and miRNA expression appear to contribute in determining the metastatic route. We went through each step of the metastasis process comparing hematogenous to peritoneal spread. We identified differences with respect to organotropism, epithelial-mesenchymal transition, angiogenesis and inflammation, and tumor microenvironment which will be further elucidated in this review. A better understanding of the underlying mechanisms and contributing factors of metastasis development in CRC has huge relevance as it is the foundation to help find specific targets for treatment of CRC.

"Heidelberg standard examination" and "Heidelberg standard procedures" - Development of faculty-wide standards for physical examination techniques and clinical procedures in undergraduate medical education.

The competent physical examination of patients and the safe and professional implementation of clinical procedures constitute essential components of medical practice in nearly all areas of medicine. The central objective of the projects "Heidelberg standard examination" and "Heidelberg standard procedures", which were initiated by students, was to establish uniform interdisciplinary standards for physical examination and clinical procedures, and to distribute them in coordination with all clinical disciplines at the Heidelberg University Hospital. The presented project report illuminates the background of the initiative and its methodological implementation. Moreover, it describes the multimedia documentation in the form of pocketbooks and a multimedia internet-based platform, as well as the integration into the curriculum. The project presentation aims to provide orientation and action guidelines to facilitate similar processes in other faculties.

Early postoperative complications after stapled vs handsewn restorative proctocolectomy with ileal pouch-anal anastomosis in 148 patients with familial adenomatous polyposis coli: a matched-pair analysis.

AIM: Restorative proctocolectomy with ileal pouch-anal anastomosis for patients with familial adenomatous polyposis (FAP) and ulcerative colitis (UC) has been modified from a transanal hand-suture after mucosectomy to a stapled ileal pouch-anal anastomosis (IPAA) without mucosectomy. Better functional results favour stapled anastomosis; however, stapled anastomosis results in higher rates of adenomas in persisting anorectal mucosa. The purpose of this study was to compare the two techniques of pouch-anal anastomosis with respect to early postoperative complications in a collective of FAP patients. METHOD: The study was performed as a matched-pair analysis. Data were obtained from a prospectively collected database. RESULTS: The overall rate of postoperative complications was higher after stapled IPAA (31% stapled vs 23% handsewn), with anastomotic stricture occurring in 24.3% (stapled) and 16.2% (handsewn) (P = 0.22). Any leakage or pelvic abscess formation after stapled anastomosis occurred within 30 days in almost all patients, whereas these were mainly diagnosed between 30 days and 6 months after handsewn IPAA. A laparoscopic approach was used in 56.7% of patients in the stapled group but in only two patients in the handsewn group. Intra-operative blood loss was significantly higher in the handsewn group (mean ± SD: 699 ± 511 ml vs 369 ± 343 ml; P < 0.0001), as was the volume of blood transfused (mean ± SD: 205 ± 365 ml vs 8 ± 49 ml; P < 0.0001). Function did not differ between the groups. CONCLUSION: There was a nonstatistically significant tendency towards a higher rate of early postoperative complications after stapled IPAA. The timing of anastomotic leakage and abscess formation differed between the groups.

[The competent surgeon. Bridging the gap between undergraduate final year and postgraduate surgery training]. / Der kompetente Chirurg. Brückenschlag zwischen der Ausbildung im Praktischen Jahr und der chirurgischen Weiterbildung.

Competency-based frameworks rely on relevant professional competency rather than formal regulations. The transitional phase between final year undergraduate and common trunk postgraduate medical training is characterized by an increase of professional responsibility whereby previously acquired knowledge, skills and abilities have to be merged and applied to patients. Undergraduate and postgraduate training programs should ensure a successive transfer of responsibility for medical practice to final year students and young residents depending on individual competence. The concept of entrustable professional activities (EPA) represents a curricular concept based on concrete medical tasks which may be assigned to the responsibility of the trainee.

Desmoid tumour biology in patients with familial adenomatous polyposis coli.

BACKGROUND: Familial adenomatous polyposis (FAP) is caused by mutations in the adenomatous polyposis coli (APC) gene. Desmoid tumours affect up to 26 per cent of patients and contribute significantly to death. This study aimed to assess the influence of sex and mutation site on desmoid tumour development and sex-specific genetic differences in patients with FAP with and without desmoid tumours. METHODS: Patients with FAP-associated desmoid tumours recorded in the Heidelberg Polyposis Register between 1991 and 2010 were identified. These patients were analysed with respect to clinical parameters and possible risk factors. RESULTS: Some 105 patients with FAP-associated desmoid tumours of a total of 585 patients with FAP were analysed. Male patients had a significantly greater number of desmoid tumours and a larger tumour mass, although tumours were more common in female patients. Desmoid tumours in male patients were located more often in the abdominal wall. Seventy-nine (75.2 per cent) of the 105 patients demonstrated a clear temporal association between a previous operation and subsequent desmoid tumour development; most of these patients were female. Mutation sites in male patients were limited to exons 5, 14 and 15, whereas female patients carried mutations along the entire coding region of the APC gene. Twenty-one per cent of patients with desmoid tumours carried mutations within the 'desmoid region', compared with only 4.1 per cent of the control group without desmoids. CONCLUSION: There are significant sex differences concerning desmoid tumour manifestation. Female patients appear to have a higher risk of desmoid tumour occurrence independent of the mutation site, whereas in male patients the mutation site seems to exert more influence.

[Attitude of medical students towards a surgical career - a global phenomenon?]. / Einstellung von Studierenden zu einer chirurgischen Karriere - ein globales Phänomen?

INTRODUCTION: Within the last few years several reports have observed an increasing decline of interest for medical students to become a general surgeon. A recent study among medical students from five medical schools in South-West Germany revealed that only 8.9 % of the students were considering a surgical career. In addition, the authors showed that there was a severe decrease of interest in a surgical career throughout medical school. The aim of the presented study is to analyse career preferences of medical students in several countries. METHODS: A Medline search for "surgical career", "medical students + general surgery" and "surgical career + influences" was performed. RESULTS: There are similar situations to that in Germany in the USA, Great Britain, New Zeeland and Switzerland with small proportions of medical students inclined towards a surgical career. In Kenya, Jordan, Pakistan and Iraq at least a higher percentage of male medical students favoured a surgical career. Independent of the country, more male medical students are pursuing a surgical career. Studies from different countries reported an increasing loss of interest in a surgical career throughout medical school. Positive influencing factors for specialisation in a field of surgery were identified: These are independent of the country, positive experiences in practical courses and positive role models. CONCLUSION: Further studies to analyse factors influencing students throughout medical school are required in the future. Internships, special tutorials, and final year rotations should be used to develop individual mentoring programmes to increase the student's interest in pursuing a general surgical career.

Emergency department admissions to inpatient cardiac telemetry beds: a prospective cohort study of risk stratification and outcomes.

PURPOSE: Little is known about physicians' use of inpatient cardiac telemetry units among emergency department patients at risk for cardiac complications. We therefore studied the outcomes of patients admitted to inpatient telemetry beds to identify a subset of patients from whom cardiac monitoring could be withheld safely. SUBJECTS AND METHODS: We conducted a prospective cohort study of 1, 033 consecutive adult patients admitted to an inpatient telemetry unit from the emergency department of a 700-bed urban public teaching hospital. Subjects with or without chest pain were risk-stratified using a prediction rule and observed for in-hospital cardiac complications, acute myocardial infarction, and transfer to an intensive care unit (ICU). RESULTS: There were no significant differences between patients with (n = 677) or patients without chest pain (n = 356) in the rates of major cardiac complications, myocardial infarctions, or transfers to an ICU. Among 318 patients with chest pain who were classified as being very low risk, none suffered major complications (negative predictive value 100%; 95% confidence interval [CI]: 98.8% to 100%). Among 214 very low risk patients without chest pain, 1 (0.5%) had a major complication (negative predictive value 99.5%; 95% CI: 97.4% to 99.9%). CONCLUSIONS: The prediction rule accurately identified patients with or without chest pain who were at very low risk of major complications, identifying a subset from whom cardiac monitoring could be withheld safely.

Teaching residents evidence-based medicine skills: a controlled trial of effectiveness and assessment of durability.

OBJECTIVES: To measure the effectiveness of an educational intervention designed to teach residents four essential evidence-based medicine (EBM) skills: question formulation, literature searching, understanding quantitative outcomes, and critical appraisal. DESIGN: Firm-based, controlled trial. SETTING: Urban public hospital. PARTICIPANTS: Fifty-five first-year internal medicine residents: 18 in the experimental group and 37 in the control group. INTERVENTION: An EBM course, taught 2 hours per week for 7 consecutive weeks by senior faculty and chief residents focusing on the four essential EBM skills. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was performance on an EBM skills test that was administered four times over 11 months: at baseline and at three time points postcourse. Postcourse test 1 assessed the effectiveness of the intervention in the experimental group (primary outcome]; postcourse test 2 assessed the control group after it crossed over to receive the intervention; and postcourse test 3 assessed durability. Baseline EBM skills were similar in the two groups. After receiving the EBM course, the experimental group achieved significantly higher postcourse test scores (adjusted mean difference, 21%; 95% confidence interval, 13% to 28%; P < .001). Postcourse improvements were noted in three of the four EBM skill domains (formulating questions, searching, and quantitative understanding [P < .005 for all], but not in critical appraisal skills [P = .4]). After crossing over to receive the educational intervention, the control group achieved similar improvements. Both groups sustained these improvements over 6 to 9 months of follow-up. CONCLUSIONS: A brief structured educational intervention produced substantial and durable improvements in residents' cognitive and technical EBM skills.