Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group.

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

[Operation time for suprapubic transumbilical cholecystectomy: Results of a prospective randomized trial]. / Operationszeit bei der suprapubisch-transumbilikalen Cholezystektomie : Ergebnisse einer prospektiv-randomisierten Studie.

BACKGROUND: Over the last decade new innovative minimally invasive techniques (e.g. transvaginal cholecystectomy and single incision laparoscopic cholecystectomy) have been developed to reduce operative trauma, postoperative pain and to achieve better cosmetic results. Nevertheless, most of these techniques are more difficult and time-consuming than conventional laparoscopic cholecystectomy (CLC). A new approach, the Minden technique for combined suprapubic transumbilical cholecystectomy (MI-CHE) has been proven to provide a very good cosmetic outcome with reduced operative trauma. The aim of this study was to survey whether MI-CHE prolongs operation times to a relevant degree compared to CLC. METHODS: A total of 40 patients undergoing laparoscopic cholecystectomy were randomized between both techniques. The duration of the operation and other perioperative data were recorded. Surgery was performed by four resident surgeons who had not yet performed any technique of laparoscopic cholecystectomy, neither MI-CHE nor CLC but were assisted by the same senior staff surgeon in all cases. The two patient groups showed no differences in age, gender and body mass index. The study was registered (DRKS00003271). Non-inferiority was tested using 95% confidence intervals (95% CI). RESULTS: The mean operation time was shorter by - 4.2 min (95% CI, + 6.4 min to - 14.8 min) in the MI-CHE as compared to the CLC group (65.5 min versus 69.7 min). There were no open conversions but in one patient intestinal injury occurred during the umbilical mini-laparotomy. There were no differences in patient satisfaction and perioperative pain between both procedures. CONCLUSION: The MI-CHE, which provides very good cosmetic results, is not more time-consuming than CLC. Additionally, it seems to be safe and not more difficult to learn than CLC.

[Knife injury to the thoracic aorta and spinal cord. Report on an"almost-mistake"]. / Messerstichverletzung von thorakaler Aorta und Myelon. Bericht über einen "Beinahe-Fehler".

We report the surgical treatment of a thoracic knife injury with lesions of the aorta and the myelon. An initially incomplete revision of the wound nearly resulted in a critical situation. Complete revision of a wound is obligatory in a penetrating injury, when a relevant structure is possibly injured.

[Mesh-wrapping of a traumatised liver with active bleeding: a subsequent complication--obstruction of the inferior vena cava]. / Hepatorrhaphie mittels Vicrylnetz bei Leberruptur Grad IV - Eine mögliche Komplikation: Verschluss der V. cava inferior.

In multiply traumatised patients injuries of the -liver are frequently seen. Depending on location and extent of the trauma, different techniques can be applied. In the presented case of a central liver trauma in a 21-year-old man with active bleeding, mesh-wrapping of both liver lobes was applied to achieve control of the bleeding. Postoperatively the patient developed constant hypertension, oliguria and severe anasarka of the lower half of the body caused by a near total obstruction of the inferior vena cava. After removal of the wrappings, all symptoms slowly disappeared. This case and the findings in similar cases in the literature suggest that there is an indication for wrapping a traumatised liver rather with diffuse and peripheral bleeding than with a central liver trauma.

Objective evaluation of minimally invasive surgical skills for transplantation. Surgeons using a virtual reality simulator.

BACKGROUND: The learning curve in laparoscopic surgery may be associated with higher patient risk, which is unacceptable in the setting of kidney donation. Virtual reality simulators may increase the safety and efficiency of training in laparoscopic surgery. The aim of this study was to investigate if the results of a training session reflect the actual skill level of transplantation surgeons and whether the simulator could differentiate laparoscopic experienced transplantation surgeon from advanced trainees. SUBJECTS AND METHODS: 16 subjects were assigned to one of two groups: 5 experienced transplantation surgeon and 11 advanced residents, with only assistant role during transplantation. The level of performance was measured by a relative scoring system that combines single parameters assessed by the computer. RESULTS: The higher the level of transplantation experience of a participant, the higher the laparoscopic performance. Experienced transplantation surgeons showed statistically significant better scores than the advanced group for time and precision parameters. CONCLUSIONS: Our results show that performance of the various tasks on the simulator corresponds to the respective level of experience in transplantation surgery in our research groups. This study confirms construct validity for the LapSim. It thus measures relevant skills and can be integrated in an endoscopic training and assessment curriculum for transplantations surgeons.

[Simulation of endoscopic procedures--an innovation to improve laparoscopic technical skills]. / Simulation d'operations endoscopiques--innovation dans le développement de la dextérité manuelle en chirurgie laparoscopique.

BACKGROUND: Laparoscopic surgery is a technically more demanding procedure compared to open surgery. Safe realistic training and unbiased quantitative assessment of technical skills are required for laparoscopic surgery. Virtual reality (VR) simulators may be useful tools for training and assessing basic and advanced surgical skills and procedures. AIM: to assess the acquisition of laparoscopic skills using virtual reality simulators. METHODS: systematic review of the literature. RESULTS: (1) The simulator can be used to objectively assess the laparoscopic skills of surgeons and distinguish between novices and experienced laparoscopic surgeons. (Evidence level III-B) (2) The target group as well as the benefit of a three-day practical course for laparoscopic surgery can be determined by the simulator. (Evidence level III-C) (3) Novices in laparoscopic surgery seem to benefit mostly from simulation training. (Evidence level III-B) (4) Steepness and plateau of a learning curve may be more dependent on the level of performance required by the particular training session rather than the number of repetitions during a training session. (Evidence level III-B) (5) Clinical background and understanding of the clinical value of a training program lead to faster acquisition and improvement of laparoscopic skills as performed on the laparoscopy simulator. (Evidence level III-B) (6) Non technical skills such as visual-spatial perception and stress coping positively correlates with virtual laparoscopic skills. (Evidence level III-B). CONCLUSION: To date, the best method for teaching laparoscopic surgery has not been defined. However, the use of virtual simulators for laparoscopy training is useful when learning basic techniques allow the surgeon to improve hand dexterity and coordination in laparoscopic surgery.

Comparison of minimally invasive surgical skills of neurosurgeons versus general surgeons: is there a difference in the first exposure to a virtual reality simulator?

OBJECTIVE: The increasing use of minimally invasive surgery, which has a longer learning curve compared to open surgery lets the necessity to develop training programs to improve endoscopic skills of trainees become ever clearer. The aim of this study was to compare the endoscopic skills of neurosurgeons versus general surgeons at first exposure to a virtual reality simulator. METHODS: 72 general surgeons who visited the 122nd Conference of the German Surgeons Society (DGCH in Munich 2005) and 35 neuroendoscopic surgeons, who visited the Third World Conference of the International Study Group of Neuroendoscopy (ISGNE in Marburg 2005) participated in this study. Each participant performed the basic module "clip application" on the virtual reality simulator (LapSim). All participants were given the same pretest instructions. Time to complete the task, error score and economy of motion were recorded. RESULTS: The general surgeons performed the clip application faster, but with more errors than neuroendoscopic surgeons. However, the difference of both parameters was not significant. Both surgeon groups have a similar score for economy of motion. CONCLUSION: Although neuroendoscopic surgeons were exposed to a foreign procedure and unfamiliar equipment, they were able to perform virtual endoscopy with similar accuracy as general surgeons, who are adapted to these endoscopic instruments and procedures and do these daily.

Spatial perception predicts laparoscopic skills on virtual reality laparoscopy simulator.

OBJECTS: This study evaluates the influence of visual-spatial perception on laparoscopic performance of novices with a virtual reality simulator (LapSim(R)). MATERIALS AND METHODS: Twenty-four novices completed standardized tests of visual-spatial perception (Lameris Toegepaste Natuurwetenschappelijk Onderzoek [TNO] Test(R) and Stumpf-Fay Cube Perspectives Test(R)) and laparoscopic skills were assessed objectively, while performing 1-h practice sessions on the LapSim(R), comprising of coordination, cutting, and clip application tasks. Outcome variables included time to complete the tasks, economy of motion as well as total error scores, respectively. RESULTS: The degree of visual-spatial perception correlated significantly with laparoscopic performance on the LapSim(R) scores. Participants with a high degree of spatial perception (Group A) performed the tasks faster than those (Group B) who had a low degree of spatial perception (p = 0.001). Individuals with a high degree of spatial perception also scored better for economy of motion (p = 0.021), tissue damage (p = 0.009), and total error (p = 0.007). CONCLUSION: Among novices, visual-spatial perception is associated with manual skills performed on a virtual reality simulator. This result may be important for educators to develop adequate training programs that can be individually adapted.

Negative stress-coping strategies among novices in surgery correlate with poor virtual laparoscopic performance.

BACKGROUND: This study explored the impact of habitual stress-coping strategies on the laparoscopic performance of novices in surgery using a virtual reality simulator. METHODS: The SVF78 stress-coping questionnaire was administered to 12 medical students in their final year of medical school (camera holders) and to 12 inexperienced surgical residents (postgraduate years 1-3). The questionnaire included devaluation during stressful situations, distractions from stressful situations, control over stressful reactions and negative coping strategies such as stress avoidance and need for social support. Assessment of laparoscopic dexterity was based on the results of performance on a virtual reality simulator. The variables of time taken to complete the task, errors and economy of motion were analysed, with a higher score indicating poor performance. Pearson and non-parametric Spearman correlations were used to compare the subjects' results on the SVF78 with those on the LapSim. RESULTS: Time taken to complete the task correlated with high values in distractive stress-coping strategies (P = 0.002) and high values in negative stress-coping strategies (P = 0.042). CONCLUSION: Ineffective stress-coping strategies correlate with poor virtual laparoscopic performance. The need for effective intraoperative stress-coping strategies is evident.

[Instituting a surgical skills lab at a training hospital]. / Einrichtung eines chirurgischen Trainingslabors an einer Ausbildungsklinik.

The improvement of surgical skills of trainees in Germany often occurs solely in the operating room. In recent years, several countries have established surgical skills labs as an essential part of surgical education, with the goal of improving and refining surgical skills before clinical application. Several years ago, training units were established by the industry wherein the curricula focused on products of the respective company. Selected training courses are still offered in a few clinics. Presently, laboratories which train the surgical skills of novices in an individually adapted form are lacking. A surgical skills lab with a comprehensive curriculum of training courses was introduced at the University Hospital of Marburg in 2005. The present article describes the development and introduction of such facilities. The authors are convinced that surgical skills labs will become increasingly important in German surgical education for improving patient safety in the operating room.

Clinical background is required for optimum performance with a VR laparoscopy simulator.

OBJECTIVE: To determine the role of clinical background when assessing the learning effect using a virtual-reality (VR) laparoscopy simulator (LapSim). MATERIALS AND METHODS: Test subjects were 12 final-year medical students (Group A) and 12 inexperienced residents (Group B) with no previous experience of VR simulators. First, to establish a baseline, both groups performed the "clip application" task twice. They then completed a training program of increasing difficulty (coordination, cutting and clip application), after which both groups were re-tested using a difficult level of the "cutting" task as an endpoint measurement. Time to complete the tasks, as well as trauma and precision parameters, were scored. RESULTS: Before training, times to complete the baseline task, as well as parameters of trauma and precision, were similar for both groups. After training, Group B (residents) completed the cutting task significantly faster than Group A (students). However, the former group also showed significant improvement in trauma and precision parameter scores in the endpoint measurement. CONCLUSION: These results suggest that clinical background and understanding of the clinical value of a training program lead to faster acquisition and improvement of laparoscopic skills as performed on the laparoscopy simulator. Thus, medical students or other personnel not involved in practical surgery may be unsuitable as candidates for assessing the value of a VR training program.

Short-term preoperative radiotherapy in rectal cancer patients leads to a reduction of the detectable number of lymph nodes in resection specimens.

BACKGROUND AND AIMS: The Union Internationale Contre le Cancer and American Joint Committee on Cancer classification propose that pN(0)-classified colorectal lymphadenectomy specimens will ordinarily include 12 or more tumor-negative lymph nodes. We performed a clinical trial to investigate whether a short-term preoperative radiotherapy (5x5 Gy) leads to a reduction of the number of lymph nodes in rectal cancer specimens after total and partial mesorectal excision (TME and PME, respectively). MATERIALS AND METHODS: Within a 5-year period, 28 (15%) of 148 rectal cancer patients underwent hypofractionated preoperative radiotherapy in this monocenter study, whereas 120 patients (85%) underwent TME/PME surgery alone. The main criterion was the number of lymph nodes in TME/PME specimens. We used a stratified one-sided Wilcoxon-Mann-Whitney test to test for a significant difference in the number of lymph nodes, stratifying for tumor location and postoperative tumor stage. Patients who were suspected of having any alterations in the number of pelvic lymph nodes were excluded from the study. RESULTS: Fewer lymph nodes were detected in the TME/PME specimens of patients who received hypofractionated preoperative radiotherapy compared to patients who underwent TME/PME surgery alone (12 detectable lymph nodes vs 15; p=0.0005). Tumor location (p=0.095) and tumor stage (p=0.093) did not significantly influence the number of lymph nodes in this study. CONCLUSIONS: We conclude that a 5x5 Gy short-term preoperative radiotherapy leads to a reduction in the number of lymph nodes in TME/PME specimens. Because neoadjuvant therapy in rectal cancer for T(2) and T(3) tumors has advanced a new therapeutic standard procedure, in the future, less lymph nodes will be detected in TME/PME specimens. This might influence the required number of lymph nodes in current staging systems for rectal cancer in the future.

Successful treatment of solid-pseudopapillary tumor of the pancreas with multiple liver metastases.

The solid-pseudopapillary tumor (SPT) is a very rare pancreatic neoplasm that predominantly affects young females. About 450 cases have been described in the world literature and approximately 20% of the reported patients were children. The occurrence of SPT with distant metastases in children is extremely rare with only two previously reported cases. We now report a 16-year-old Asian girl with a large SPT and synchronous multiple liver metastases who was successfully treated in a 2-step strategy, including initial pylorus-preserving partial duodenopancreatectomy, right hemicolectomy, resection and allografting of the portal vein and secondary resection of 12 liver metastases. The patient is disease free after a follow-up of 18 months after resection of the primary tumor, suggesting that an aggressive surgical treatment might also be justified for metastasized SPT.

Beet-vinasse (condensed molasses solubles) as an ingredient in diets for cattle and pigs - nutritive value and limitations.

Sugar beet vinasse, originating as the condensed molasses residue from yeast production, was fed to bulls and pigs to determine the feed value. It contained, per kg dry matter (DM content 66.8%), 293 g crude protein, 305 g N-free extract (therefrom 34.4 g total sugar), and 395 g crude ash. The experiment was carried out with three fattening bulls (German Holstein) and four adult pigs (Gottingen Minipig). In bulls, two balance trials lasting 20 days each (10 days adaptation; 10 days collection) were conducted in which subsequently a basal ration without and with vinasse (14% in DM) was fed. In pigs, the experiment consisted of three 12-day balance trials with the final 5 days as collection period. In the first trial, pigs received a basal diet without vinasse and in the following, a mixed diet with 16 and 43% vinasse (in DM) respectively. Digestibilities of components in vinasse in bulls were: organic matter 73.5%, crude protein 72.6%, and N-free extract 52.3%. In bulls, no influence on faeces quality could be detected while feeding 14% vinasse in DM. While feeding 16% vinasse in DM to pigs, the digestibility of organic matter amounted to 72.3% (crude protein 71.8%; NfE 74.6%). Feeding higher amounts of vinasse (43% in DM) in the diet of pigs, digestibilities were reduced (organic matter: 61.6%), which might be a result of a reduced retention time of the chyme as a result of an osmotically driven diarrhoea because of unexpectedly high sulphate (136 g/kg DM) content in the vinasse. It is concluded that because of organic matter digestibility >70% for cattle and pigs, the use of vinasse in these species in small proportions is reasonable.

[A virtual reality simulator for objective assessment of surgeons' laparoscopic skill]. / Laparoskopiesimulator Abbildung der manuellen Geschicklichkeit in der laparoskopischen Chirurgie.

BACKGROUND: The aim of this study was to validate computed virtual reality simulation as a tool to assess laparoscopic skills and to establish whether the simulator allows differentiating between surgeons with different laparoscopic experience. METHODS: 27 physicians at the surgical department of the University of Marburg, Germany, with different experience in laparoscopic surgery were divided into three groups: experienced (group I), intermediate (group II), and novices (group III). Following a brief introduction to the virtual reality simulator (LapSim), each participant performed twice a training program consisting of seven tasks (examinations I and II). RESULTS: Comparison of experienced surgeons with less experienced laparoscopic physicians showed a significant (P<0.05) superiority of group I at examinations I and II in most exercises. The groups' difference was more obvious in examination II, since the technique was new for all participants during examination I. Tasks of low complexity in virtual reality such as camera navigation, which are performed by young, not yet responsible surgeons in real surgery, did not show significantly different results between the three groups. CONCLUSION: Differences in laparoscopic experience can be visualised with a virtual reality simulator, and thus a simulator is helpful for assessing surgeons' laparoscopic skills.

[High-grade intimal sarcoma in an aneurysm of the infrarenal aorta]. / Hochmalignes Intimasarkom in einem Aneurysma der infrarenalen Bauchaorta.

Primary intimal sarcomas of the aorta are extremely rare and aggressive tumors metastasizing into bones and visceral organs including liver, kidneys, adrenal glands, and lung. The first symptoms are often nonspecific and often caused by arterial embolism. We report a case with an incidental finding of primary intimal sarcoma in an aneurysm of a patient with claudication due to tumor embolization.

[Neuroendocrine tumors of the gastrointestinal tract (NETGI) and second primary malignancies--which is dominant?]. / Neuroendokrine Tumoren des Gastrointestinaltraktes (NETGI) und Zweitkarzinome. Welche Erkrankung tritt klinisch in Erscheinung?

INTRODUCTION: 13-46% of all patients with a neuroendocrine tumor of the gastrointestinal tract (NETGI, "Carcinoid") develop a carcinoma. The goal of our study was to find out the frequency of other malignancies in our patients with an NETGI and to discover which of the tumors was decisive for the clinical course. PATIENTS AND METHODS: We documented the clinical findings in 55 patients with an NETGI who underwent surgery in our hospital, noted the occurrence of other malignancies and recorded a current follow-up. RESULTS: 13 of 55 patients (24%) had an additional carcinoma after a median follow-up of 53 months. In 11 of the 13 patients the NETGI was identified accidentally. None of them had developed the carcinoma after the NETGI. CONCLUSION: In most of our patients (11 out of 13) the carcinoma was clinically predominant and discovered before the NETGI. Thus, a special follow-up looking for a carcinoma is probably not mandatory after the diagnosis of an NETGI.

German national case collection of familial pancreatic cancer - clinical-genetic analysis of the first 21 families.

BACKGROUND: The observation of a familial accumulation of ductal pancreatic adenocarcinoma (PC) and the increased risk for PC in certain hereditary tumor syndromes point to a genetic predisposition for PC. In order to evaluate the characteristics of familial PC, a German national case collection for familial pancreas cancer (FaPaCa) was established. PATIENTS AND METHODS: In FaPaCa, families of patients with PC are being collected, who have at least 1 first-degree relative with PC or with malignant melanoma. Histopathologic verification of tumor diagnoses, acquisition of clinical data, and full genetic counselling are prerequisites for the enrollment of PC families in FaPaCa. RESULTS: So far, 21 families fulfilled the criteria for partaking in FaPaCa. In 11 families, PC represented the sole tumor entity. Additional tumors included malignant melanoma in 5, breast cancer in 3, and prostatic, colon or lung cancer in 2 families. Compared to the preceding generation, a younger age at diagnosis of PC was observed in the offspring of PC patients (offspring median 53 years vs. parents median 75.5 years). CONCLUSION: The association of PC and breast cancer, and of PC and malignant melanoma suggests predisposing mutations in the BRCA2 or CDKN2A genes in about one third of the FaPaCa families. Mutational analyses in both candidate genes may help to identify individuals who are at an increased risk for developing PC. A shift towards a younger age at diagnosis in our PC families may indicate genetic anticipation and/or changes of patterns of exogenous risk factors.