Radiological Changes After Resection Rectopexy in Patients with Rectal Prolapse-Influence on Clinical Symptoms and Quality of Life.

BACKGROUND: Resection rectopexy is performed to correct the anatomic defect associated with rectal prolapse. The aim of the study was to determine whether the change in the radiological prolapse grade has an influence on patients' symptoms and quality of life. METHODS: The study investigated 40 patients who underwent resection rectopexy for rectal prolapse. The following were determined before and after surgery: radiological prolapse grade, anorectal angle and pelvic floor position in defecography, clinical symptoms (Cleveland Clinic Incontinence and Constipation Scores, Kelly-Hohlschneider Score), quality of life. RESULTS: Defecography revealed postoperative improvement in the prolapse grade and pelvic floor position (p < 0.05). The clinical symptoms and quality of life improved in both, the total population (n = 40) and in patients with improved radiological prolapse grade (n = 30): all clinical scores (p < 0.05), SF-36 (vitality, social role, mental health p < 0.05), and Fecal Incontinence Quality of Life Scale (lifestyle, coping, embarrassment p < 0.05). Patients without improved radiological findings showed no change in their symptoms or quality of life. CONCLUSION: Our study demonstrates that the radiological prolapse grade is improved by resection rectopexy. Correction of the anatomic defect was associated with improvement in symptoms and quality of life. Defecography may therefore be useful in the postoperative assessment of persistent symptoms or reduced quality of life.

Influence of pelvic volume on surgical outcome after low anterior resection for rectal cancer.

BACKGROUND: Low anterior resection (LAR) for rectal cancer is a potentially challenging operation due to limited space in the pelvis. CT pelvimetry allows to quantify pelvic space, so that its relationship with outcome after LAR may be assessed. Studies investigating this, however, yielded conflicting results. We hypothesized that a small pelvis is associated with a higher rate of incomplete mesorectal excision, anastomotic leakages, and increased rate of urinary dysfunction in patients operated for rectal cancer. METHODS: In a single-center retrospective analysis, we studied 74 patients that underwent LAR for rectal cancer with primary anastomosis. Thin-layered multi-slice CT datasets were used for slice by slice depiction of the inner pelvic surface, and the inner pelvic volume was automatically compounded. The primary outcome was quality of total mesorectal excision (TME; Mercury grading); secondary outcomes were anastomotic leakage and urinary dysfunction with regard to pelvic dimensions. Univariate analyses and multiple logistic regression analyses were performed for the primary and the secondary outcomes. RESULTS: Shorter obstetric conjugate diameters were associated with a higher probability of a worse TME quality (110.8 ± 10.2 vs. 105.0 ± 8.6 mm; OR 0.85; 95% CI 0.73-0.99; p = 0.038). Short interspinous distance showed a trend towards an increased risk for deteriorated TME quality (OR 0.88; 95% CI 0.76-1.0; p = 0.06). Anastomotic leakage was associated with anemia (OR 2.77; 95% CI 1.0-7.7; p = 0.047). Association between pelvic diameters or pelvic volume and anastomotic leakage or urinary dysfunction was not observed. Perioperative blood transfusions were administered more often in patients with postoperative urinary dysfunction (OR 17.67; 95% CI 2.44-127.7; p = 0.004). CONCLUSION: Shorter obstetric conjugate diameter might be a risk factor for incompleteness of total mesorectal excision. Anastomotic leakage seems to be influenced more by clinical factors such as anemia rather than pelvic dimensions. Further studies have to prove the influence of pelvic diameter on local recurrence of rectal cancer after LAR.

Impact of intraoperative microperfusion assessment with Pinpoint Perfusion Imaging on surgical management of laparoscopic low rectal and anorectal anastomoses.

AIM: Inadequate intestinal blood flow may contribute to anastomotic leakage accounting for substantial morbidity and mortality in colorectal surgery. Precise intraoperative assessment of microperfusion may have an impact on the surgeons intraoperative management and leakage rate. METHOD: In this single center observational study we implemented and integrated intraoperative indocyanin green (ICG) based microperfusion assessment of anastomosis with Pinpoint Perfusion Imaging in a series of consecutive rectal cancer patients who underwent laparoscopic anterior and lower anterior resection with primary anastomosis during a 5-months period. RESULTS: We could demonstrate the feasibility and safety of intraoperative fluorescence angiography for colorectal microperfusion assessment. Technology implementation was immediately successful. No adverse effects have been documented related to fluorescent dye. Microperfusion angiography of the colon succeeded in all cases and assessment of perfusion imaging influenced surgical decision making in 28% of the patients, of which all patients showed primary healing of the anastomosis. We found a leakage rate of 6% with one leakage of a coloanal anastomosis in all patients. CONCLUSION: Fluorescence angiography is an accurate tool for assessing microperfusion and is most likely associated with improved outcomes with regard to anastomotic healing.

Local facial cutaneous vasoconstriction: an unusual complication of inhaled racemic epinephrine in a neonate.

A term infant treated for post-extubation stridor with nebulized racemic epinephrine developed localized facial blanching due to cutaneous absorption of the aerosolized vasoconstrictor. Local application of heat restored circulation to the afflicted area. This complication of a commonly used medication is not previously reported in the medical literature and has the potential for severe sequelae.

[Proctocolectomy in ulcerative colitis : is a multistep procedure in cases of immunosuppression advisable?]. / Die Proktokolektomie bei Colitis ulcerosa : Ist ein mehrzeitiges Vorgehen bei Immunsuppression sinnvoll?

BACKGROUND: The coloproctomucosectomy (CPM) is the procedure of the choice for the surgical treatment of ulcerative colitis (UC). In cases with pronounced immunosuppression (IS), a 3-step (3S) procedure [i.e., subtotal colectomy and ileal pouch-anal anastomosis (IPAA) and finally ileostomy reconstruction] is often selected. Fewer perioperative complications can be expected compared to the 2-step (2S) procedure; however, an additional in-hospital stay and surgical intervention are necessary. The aim of the present study was to compare both approaches using the clinical outcome of our patients undergoing IPAA to determine efficacy of these two concepts. PATIENTS AND METHODS: From 1997-2010, a total of 225 patients were operated using a 2S or 3S IPAA procedure. Clinical outcomes were evaluated based on the number of surgical steps for the ileoanal pouch procedure and IPAA. The survey was performed within the scope of prospective study. RESULTS: Of the 225 patients with CPM, 66 were excluded due to a diagnosis other than UC (familial adenomatous polyposis, indeterminate colitis, Crohn's disease) and patients with permanent ILS procedures without the possibility or wish for an IPAA (n = 54). Included were 71 patients with 2S (w = 30, m = 41) and 34 patients with 3S procedures (w = 21, m = 13). Compared to the 2S procedure, the 3S procedure was shown to have shorter operation times (246 versus 296 min; p = 0.05), shorter hospital stays (15.5 versus 24.6 days; p = 0.05), shorter intensive care unit stays (3.3 versus 7.2 days; p = 0.05), and fewer major complications (5.9 % versus 22.5 %; p = 0.035). Patients with 3S procedures had a higher BMI (26.2 versus 23.1 kg/m²; p = 0.05) and fewer required IS (10 % vs. 62 %; p < 0.05). CONCLUSION: The decision for a 3S procedure in UC and pronounced IS is advisable and justified. Using a 3S procedure, immunosuppression and its influence on perioperative morbidity are thus reduced. The IPAA can be performed with shorter operation times, shorter hospital stays and fewer major complications.

[What is the actual benefit of sigmoid resection for acute diverticulitis? : Functional outcome after surgical and conservative treatment]. / Welchen Erfolg bringt die Sigmaresektion bei der akuten Sigmadivertikulitis tatsächlich? : Funktionelle Ergebnisse nach operativer und konservativer Therapie.

INTRODUCTION: The correct therapeutic management of acute sigmoid diverticulitis (SD) is still controversially discussed. Essential to the success of therapy is primarily the long-term resolution of Patient symptoms after surgical or conservative therapy. The aim of this study was to compare the long-term outcome after conservative and surgical treatment of Patients with acute SD. PATIENTS AND METHODS: Consecutive admissions of all Patients with acute SD were prospectively recruited from January 2005 to June 2008 with the exception of a free perforation. The following data were recorded: age, sex, first or recurrent episode of SD, computed tomography (CT) stage, white blood cell count, C-reactive protein, persistent symptoms and recurrence after conservative and surgical therapy. Furthermore, information on the rates of postoperative sexual and bladder dysfunction was collected. The long-term outcome was evaluated by a standardized questionnaire. In June 2008 all Patients were contacted using a standardized questionnaire. RESULTS: A total of 153 Patients were included in the study of whom 70 (45.8  %) presented with the first episode, 83 (54.2  %) had a prior history of SD and 40 Patients were treated conservatively whereas 113 Patients were surgically treated by sigmoid resection. Uncomplicated SD was seen in 16 Patients (conservative 4, surgical 12, p = 0.961), phlegmonous SD was seen in 88 cases (conservative 29, surgical 59, p = 0.026) and covered perforated SD in 49 cases (conservative 7, surgical 42, p = 0.022). The median follow-up was 32 months (range 12-52 months). At follow-up 25  % of conservative and 8.8  % of Patients treated surgically complained about persistent symptoms (p = 0.009). The following symptoms occurred (conservative vs. surgery): painful defecation (22.5  % versus 8.8  %, p = 0.024.), constipation (25  % versus 8.8  %, p = 0.009), abdominal cramp (22.5 % versus 4.4  %, p = 0.001) and painful flatulence (25  % versus 8.8  %, p = 0.009). Sexual or bladder dysfunction occurred postoperatively in 7  % and 9  %, respectively. Of the conservatively treated Patients 32.5  % had a recurrence of SD during follow-up compared to 3.5 % of surgically treated Patients (p < 0.001). CONCLUSIONS: Surgical treatment of acute SD is more effective than conservative therapy for the prophylaxis of recurrent SD and avoidance of persistent symptoms.

[Personalized treatment of colorectal cancer in old age]. / Individualisierte Therapie des kolorektalen Karzinoms im hohen Alter.

The incidence of colorectal cancer in elderly patients is rising. Due to changing demographics the topic of personalized treatment of colorectal cancer in old age is of growing importance for interdisciplinary tumor therapy. Besides the oncological results for this group of patients, aspects of risk consideration for treatment, quality of life and the personal conception of life become more relevant. This report covers the changes in comorbidities associated with old age and illustrates the impact on therapeutic strategies and results. Furthermore, it exemplifies potential individual adaption of standardized therapy regimens in multimorbid patients and provides information on possible strategies to improve treatment outcome.

Suitability of a virtual reality simulator for laparoscopic skills assessment in a surgical training course.

BACKGROUND: Virtual reality simulators (VRS) can acquire specific performance parameters for laparoscopic surgery. The aim of this study was to evaluate the suitability of a VRS for the assessment in a surgical skills course. MATERIALS AND METHODS: One hundred five attendees of a 7-day surgical skills course were tested with a VRS at the beginning (T1) and at the end (T2) of the course. Two standard VRS tasks (lifting and grasping (LG) and fine dissection (FD)) with two scores and 21 individual parameters were used. VRS performance was correlated to laparoscopic experience and experience in playing video games in order to assess the influence of preexisting skills. RESULTS: The participants improved significantly in both scores and in 19/21 VRS parameters between T1 and T2. Laparoscopic experts were significantly better than novices only for the parameter tissue damage on T1 in LG (41.4 %, P < 0.001). Gamers were significantly better than non-gamers in all manual parameters on T1 in LG. Both groups of laparoscopic experience as well as non-gamers improved between T1 and T2 in LG for most parameters, while gamers only improved for tissue damage. CONCLUSIONS: The VRS was able to assess the gain in surgical performance during the course in general. However, laparoscopic experience and video game experience strongly influenced the results. Laparoscopic experience was correlated to the parameter tissue damage, whereas video game experience was correlated to manual parameters. This knowledge can be used to build adequate scoring systems for VRS and to design tasks that target specific course skills.

Locally recurrent colorectal cancer: results of surgical therapy.

PURPOSE: Up to 20 % of colorectal cancer patients develop recurrent disease despite standardized surgical techniques and multimodal treatment strategies. Radical resection is the central component of curative therapy in these cases. The aim of this study was to evaluate treatment results in patients with locoregionally recurrent colorectal cancer. METHODS: From January 1995 to December 2007, surgery was performed for recurrent colorectal cancer in 82 patients who had undergone curative (R0) resection of their primary tumor. Assessment included patient, tumor and treatment characteristics, postoperative complications, and time without re-recurrence; recurrence-free and overall survival rates were calculated according to the Kaplan-Meier method. RESULTS: Resection was performed in 60 of the 82 patients (73 %), repeat R0 resection in 52 % (31/60). Patients had a postoperative morbidity of 39 % (31/82), a relaparotomy rate of 13 % (11/82), and a lethality of 7 % (6/82). Forty-eight percent of all surgically-treated patients received a permanent stoma. Re-recurrence was seen in 52 % (16/31). R0 resection was associated with a 5-year survival rate of 35 % (11/31). CONCLUSIONS: Extensive reinterventions often enable repeat R0 resection. Despite relevant morbidity, the lethality appears to be acceptable. Decisive for the prognosis is re-recurrence.

[Simulation training in surgical education - application of virtual reality laparoscopic simulators in a surgical skills course]. / Simulationstraining in der Weiterbildung - Einsatz von virtuellen laparoskopischen Operationssimulatoren in einem chirurgischen Trainingskurs.

BACKGROUND: Training and simulation are gaining importance in surgical education. Today, virtual reality surgery simulators provide sophisticated laparoscopic training scenarios and offer detailed assessment methods. This also makes simulators interesting for the application in surgical skills courses. The aim of the current study was to assess the suitability of a virtual surgery simulator for training and assessment in an established surgical training course. MATERIALS AND METHODS: The study was conducted during the annual "Practical Course for Visceral Surgery" (Warnemuende, Germany). 36 of 108 course participants were assigned at random for the study. Training was conducted in 15 sessions over 5 days with 4 identical virtual surgery simulators (LapSim) and 2 standardised training tasks. The simulator measured 16 individual parameters and calculated 2 scores. Questionnaires were used to assess the test persons' laparoscopic experience, their training situation and the acceptance of the simulator training. Data were analysed with non-parametric tests. A subgroup analysis for laparoscopic experience was conducted in order to assess the simulator's construct validity and assessment capabilities. RESULTS: Median age was 32 (27 - 41) years; median professional experience was 3 (1 - 11) years. Typical laparoscopic learning curves with initial significant improvements and a subsequent plateau phase were measured over 5 days. The individual training sessions exhibited a rhythmic variability in the training results. A shorter night's sleep led to a marked drop in performance. The participants' different experience levels could clearly be discriminated ( ≤ 20 vs. > 20 laparoscopic operations; p ≤ 0.001). The questionnaire showed that the majority of the participants had limited training opportunities in their hospitals. The simulator training was very well accepted. However, the participants severely misjudged the real costs of the simulators that were used. CONCLUSIONS: The learning curve on the simulator was successfully mastered during the course. Construct validity could be demonstrated within the course setting. The simulator's assessment system can be of value for the assessment of laparoscopic training performance within surgical skills courses. Acceptance of the simulator training is high. However, simulators are currently too expensive to be used within a large training course.

[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.

[Experiences from more than 2,100 hernia repair operations. How has the therapy changed in the last 15 years?]. / Erfahrungen aus über 2100 Hernienreparationen. Wie hat sich die Therapie in den letzten 15 Jahren verändert?

INTRODUCTION: Inguinal hernia (IH) surgery has changed fundamentally during the last 25 years due to tension-free repair, minimally-invasive approaches and growing influence of economy in medical decision making. Aim of the study was the documentation and analysis of changes in IH surgery during the last 15 years in our patient cohort. MATERIAL AND METHODS: Patients undergoing elective or emergency inguinal/femoral hernia repair from January 1995 to December 2009 were included in the study. Analysis of patient data was carried out by prospective online recording. RESULTS: A total of 1,908 patients with 2,124 IHs were treated in the study period and the number of IH repairs decreased continuously. The number of recurrent hernias peaked in 2005-2009 with 16.4%. The average preoperative hospital stay decreased from 2.4 to 0.4 days and the postoperative hospital stay from 7.0 to 3.3 days. The percentage of suture repairs declined from 54.9% in 1995 to 4.1% in 2009 and the percentage of open tension-free repairs rose to 52.9% in 1998. In the following years the majority of repairs were performed by minimally invasive procedures but in 2009 the percentage of conventional hernia repairs exceeded the rate of minimally invasive repairs. CONCLUSION: The main reason for these changes is the implementation of diagnosis-related groups which hampers inpatient repair of "simple" inguinal hernias, favors short hospital stay and does not adequately reimburse minimally invasive repairs.

Management and results of complications after anterior resection with colonic pouch reconstruction for rectal cancer.

AIM: Colonic J-pouch reconstruction is widely carried out during low anterior resection. The aim of this observational study was to describe the complications and evaluate the results of adverse event management. METHOD: A total of 128 patients underwent an elective anterior resection with colorectal or coloanal J-pouch reconstruction for primary rectal cancer between January 1997 and December 2008. RESULTS: The overall mortality was 1.6%. Three (2.3%) patients developed pouch necrosis, one of whom died. The rate of anastomotic leakage was 11.7%. Other major complications included intra-abdominal abscess (3.1%), haemorrhage (0.8%) and abdominal dihiscence (0.8%). In all cases of anastomotic leakage, the pouch was salvaged, with 80% of patients undergoing surgical revision with relaparotomy and transanal suture. Patients with pouch necrosis underwent relaparotomy with removal of the pouch and a terminal colostomy. In all cases of intra-abdominal abscess without anastomotic leakage, radiologically controlled percutaneous drainage was carried out. CONCLUSION: Anal function can usually be saved after anastomotic leakage by salvage surgery without increase in mortality.

[Perforation risk and patient age. Risk analysis in acute sigmoid diverticulitis]. / Perforationsrisiko und Patientenalter. Eine Risikoanalyse bei der akuten Sigmadivertikulitis.

INTRODUCTION: It is often postulated that younger patients with acute sigmoid diverticulitis (SD) have an increased risk of perforation which constitutes an indication for early surgery. The aim of this study was to correlate the severity of sigmoid diverticulitis with patient age in order to check the surgical indication in younger patients. PATIENTS AND METHODS: Patients with acute SD from January 1998 to June 2009 were included. Two age groups were distinguished: group I (GI) ≤40 years in age and group II (GII) >40 years. The perforation risk associated with first episode SD was determined by multivariate analysis. SD was classified according to Hansen and Stock (H/S). RESULTS: In the total cohort of 959 patients, including 86 in GI (8.9%) and 873 in GII (91.1%) 468 had a first episode, with 64 in GI (13.7%) and 404 in GII (86.3%). The proportion of first episodes was 74.4% in GI and 46.3% in GII (p<0.001). The perforation risk did not differ (H/S IIb: 29.7% in GI vs. 29.2% in GII, p=0.938; H/S IIc: 25% in GI vs. 25% in GII, p=1). Treatment regimes were (GI vs. GII) emergency operations 25% vs. 25% (p=1), elective operations 17.2% vs. 10% (p=0.096) and conservative treatment 57.8% vs. 64.9% (p=0.276). CONCLUSION: First episodes of SD were more frequent in younger patients (≤40) and did not involve a higher risk of perforation. The indication for treatment of acute SD should not be based on age but on the severity of inflammation and the individual situation of patients.

Abdominal resection rectopexy with an absorbable polyglactin mesh: prospective evaluation of morphological and functional changes with consecutive improvement of patient's symptoms.

BACKGROUND: The pathophysiology of rectal prolapse and intussusception has not yet been clarified. This is reflected in the multiplicity of surgical procedures. The aim of this prospective study was to measure morphological and functional changes of the pelvic floor and the rectum before and after resection rectopexy. METHODS: A total of 21 patients (mean age 60 years; 2 men, 19 women) with manifest rectal prolapse and rectoanal intussusception underwent sigmoidectomy and rectopexy with an absorbable polyglactin mesh graft. The following analyses were performed preoperatively and, on average, 15 months (range 6-21 month) postoperatively: radiologic defecography, rectal volumetry, sphincter manometry, and evaluation of clinical symptoms. RESULTS: Postoperatively there was no patient with rectal prolapse, and only one with an intussusception. Rectal compliance increased from 6.4 to 10.2 ml/mmHg. Rectal volumetry showed a decrease of the thresholds for the sensation of "desire to defecate" and "maximal tolerated volume" (100-75 ml, 175-150 ml). Postoperatively, there was a higher level of the pelvic floor during contraction. The anorectal angle, vector volume, radial asymmetry, sphincter length, and resting and squeezing pressures were unchanged. Surgery improved rectal evacuation (p = 0.03), continence (p = 0.01), stool consistency (p = 0.03), and warning period (p = 0.01). Patients' personal assessment showed an improved overall satisfaction. CONCLUSIONS: Resection rectopexy is a reliable method for treating rectal prolapse and rectoanal intussusception with clear improvement of the patient's clinical symptoms. The restored anorectal function can be attributed to improved rectal compliance, a lower sensory threshold, an elevation of the pelvic floor during squeezing, and an improved rectal evacuation.

Predictors of permanent ileostomy after restorative proctocolectomy.

BACKGROUND: Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is a surgical approach for ulcerative colitis and familial adenomatous polyposis. This study evaluated predictors of the need for a permanent ileostomy to identify patients at high risk of IPAA failure. METHODS: This was a retrospective analysis of patients who underwent proctocolectomy and IPAA between 1997 and 2008. A logistic regression model was used for multivariable analysis of potential risk factors. RESULTS: Proctocolectomy was combined with IPAA in 185 patients, of whom 169 had a loop ileostomy formed. IPAA and ileostomy closure were successful in 162 patients (87.6 per cent). Reasons for not closing the ileostomy included pouch failure (16 patients), patient choice (5) and death (2). Thus one in eight patients had a permanent ileostomy after planned IPAA. Age was the major predictor of the need for a permanent ileostomy in multivariable analysis (P = 0.002) with a probability of more than 25 per cent in patients aged over 60 years. However, advancing age was associated with colitis, co-morbidity, obesity and corticosteroid use. CONCLUSION: The probability of the need for a permanent ileostomy after IPAA increases with age.

Cellular senescence predicts treatment outcome in metastasised colorectal cancer.

BACKGROUND: Cellular senescence is a terminal cell-cycle arrest that occurs in response to activated oncogenes and DNA-damaging chemotherapy. Whether cancer cell senescence at diagnosis might be predictive for treatment outcome is unknown. METHODS: A senescence index (SI) was developed and used to retrospectively correlate the treatment outcome of 30 UICC stage IV colorectal cancer (CRC) patients with their SI at diagnosis. RESULTS: 5-Fluorouracil/leucovorin-treated CRC patients achieved a significantly longer progression-free survival when presenting with SI-positive tumours before therapy (median 12.0 vs 6.0 months; P=0.044). CONCLUSION: Cancer cell senescence predicts treatment outcome in metastasised CRC. Prospective analyses of larger patient cohorts are needed.

Predicting the site of origin of tumors by a gene expression signature derived from normal tissues.

Multiple expression signatures for the prediction of the site of origin of metastatic cancer of unknown primary origin (CUP) have been developed. Owing to their limited coverage of tumor types and suboptimal prediction accuracy on distinct tumors, there is still room for alternative CUP gene expression signatures. Whereas in past studies, CUP classifiers were trained solely on data from tumor samples, we now use expression patterns from normal tissues for classifier training. This approach potentially avoids pitfalls related to the representation of genetically heterogeneous tumor subtypes during classifier training. Two expression data sets of normal human tissues have been reanalyzed to derive an expression signature for liver, prostate, kidney, ovarian and lung tissues. In reciprocal validation, classifiers trained on either data set achieved overall accuracies greater than 97%. Classifiers trained on combined expression data from both normal tissue data sets were able to predict the site of origin in a cohort of 652 primary tumors with approximately 90% accuracy. Prediction accuracies of primary cancer-based classifiers were in the same range, as determined by cross-validation on this cohort. For individual tumor types, normal tissue-based classifiers achieved sensitivities in the range of 64-99% and specificities in the range of 92-100%. Primary origins for 12 of 20 metastases were predicted correctly, with false predictions highlighting the need for accurate sample preparation to avoid contaminations by metastases-surrounding tissue. We conclude that gene expression patterns of normal tissues harbor phenotypic information that is retained in tumors and can be sufficient to recover the type of primary tumor from expression patterns alone.

WITHDRAWN: Predicting the site of origin of tumors by a gene expression signature derived from normal tissues.

Multiple expression signatures for the prediction of the site of origin of metastatic cancers of unknown primary origin (CUP) have been developed. Owing to their limited coverage of tumor types and suboptimal prediction accuracy on distinct tumors there is still room for alternative CUP gene expression signatures. Whereas in past studies CUP classifiers were solely trained on data from tumor samples, we now use expression patterns from normal tissues for classifier training. This approach potentially avoids pitfalls related to the representation of genetically heterogeneous tumor subtypes during classifier training. Two expression data sets of normal human tissues have been reanalysed to derive an expression signature for liver, prostate, kidney, ovarian and lung tissues. In reciprocal validation classifiers trained on either data set achieved overall accuracies greater than 97%. Classifiers trained on combined expression data from both normal tissue data sets were able to predict the site of origin in a cohort of 652 primary tumors with approximately 90% accuracy. Prediction accuracies of primary cancer-based classifiers were in the same range as determined by cross-validation on this cohort. For individual tumor types, normal tissue-based best-centroid classifiers achieved sensitivities ranging from 71 to 99% and specificities ranging from 91 to 99%. Primary origins for 12 of 20 metastases were predicted correctly with false predictions highlighting the need for accurate sample preparation to avoid contaminations by metastases-surrounding tissue. We conclude that gene expression patterns of normal tissues harbor phenotypic information that is retained in tumors and can be sufficient to recover the type of a primary tumor from expression patterns alone.Oncogene advance online publication, 16 November 2009; doi:10.1038/onc.2009.398.

["Practical course for visceral surgery in Warnemünde" 10 years on. Significance and benefits of a surgical training course]. / Zehn Jahre "Praktischer Kurs für Viszeralchirurgie Warnemünde". Bedeutung und Nutzen eines chirurgischen Trainingskurses.

BACKGROUND: Skill courses for surgery offer a good but cost and personnel-intensive possibility to obtain practical and theoretical knowledge by the employment of a close teacher-pupil contact of a large group of surgeons. The goal of the study presented here was to evaluate the satisfaction and benefits of the practical course for visceral surgery in Warnemünde after 10 years of course experience. MATERIAL AND METHODS: All participants in the annual course for visceral surgery were included since 1999. During this 1-week course conventional and laparoscopic exercises are performed under direct guidance of an experienced tutor. The participants are divided into 3 groups based on their surgical experience (e.g. <3 years, 3-5 years, >5 years). All participants received a standardised questionnaire before and after successful course completion for the collection of relevant data (e.g. demography, training, surgical experience and course evaluation). RESULTS: A total of 1,062 participants (435 female, 627 male, mean age 37 years) participated in the course. The average surgical experience of the participants was 5 years. Of the participants 489 came from a hospital of basic medical care, 499 from a hospital of maximum medical care and 74 from a university hospital. Of the participants 96% had no or only little experience with skill courses (1,020 out of 1,065) and 827 participants had no or only few possibilities for training outside of the operation room (78%). The conventional part of the course was evaluated by 77% of the participants as very good and by 50% as very good for the laparoscopic part. Only 8.3% of the participants were willing to finance the costs of the course by themselves. CONCLUSIONS: The practical course for visceral surgery leads to a subjective success in learning. Participation in the course leads to a high satisfaction and offers a cost-intensive possibility for a standardised surgical training. But there are too few experiences with skill courses and possibilities for surgical training outside the operation room so far.