Survival outcome of non-small cell lung cancer patients: Comparing results between the database of the Comprehensive Cancer Center Zürich and the Epidemiological Cancer Registry Zurich and Zug.

BACKGROUND: Cancer cases among the population of the canton Zurich, are registered in the Cancer Registry of the cantons of Zurich and Zug (KKR). The Thoracic Oncology Center, founded in 2011 is one of 17 multidisciplinary centers within the Comprehensive Cancer Center Zurich (CCCZ). METHODS: The aim of the current study is to quantify the mortality risk of patients with NSCLC and identify differences on survival and other factors between patients receiving their primary treatment at the CCCZ and those treated elsewhere and registered by KKR. The differential effect between CCCZ and KKR cohorts on survival: overall, by stage, sex and age, is explored. Stratified log-rank and Wilcoxon tests, Cox models and restricted mean survival times (RMST) are estimated. Propensity score matching (PSM) is also used to adjust for confounding factors. RESULTS: Analysis included 848 NSCLC cases from the CCCZ and 1759 from the KKR, diagnosed between January 2011 and December 2015. At a median follow-up of 57 months, overall survival (OS) was significantly superior for patients treated at the CCCZ compared to KKR [Median OS: 36.0 months (95%CI: 31.0-45.0) and 12.0 months (95%CI: 11.0-13.0), respectively, stratified log-rank p < 0.001; adjusted HR = 1.31, (95% CI: 1.18-1.46), difference in RMST up to 72 months: 13.8 months (95%CI: 11.5-16.2), p < 0.001]. The effect of cohort was significant for stages III and IV (overall and also by sex and age). After PSM OS remained significantly superior for patients treated at the CCCZ compared to KKR. CONCLUSIONS: The survival probability for patients in the CCCZ cohort was superior to that of patients in the canton Zürich treated outside the center. This analysis provides further evidence of the importance of the volume of experience and the availability of a multidisciplinary organization and research environment, as delivered by a comprehensive cancer center, on the outcome of patients with NSCLC.

Learning curve for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions in a novel ex-vivo simulation model.

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is essential in the management of digestive cancers. However, teaching and learning this technique remain challenging due to the lack of cost-effective models. Material and methods: This was a prospective experimental study using a complete porcine upper gastrointestinal ex-vivo organ package, placed in an Erlangen Active Simulator for Interventional Endoscopy (EASIE-R), and prepared with one cyst and two solid masses (2 cm). Five fellows inexperienced in EUS-FNA were enrolled, performing 10 procedures on each lesion, alternatively. The total time, number of attempts for success, of needle view losses, and of scope handling were recorded, associated with an independent skills rating by procedure. We compared the first 15 procedures with the last 15 for each fellow. Results: The fellows successfully performed all procedures in 2 to 40 minutes, requiring 1 to 6 attempts. All (5/5) improved their total time taken (P < 0.001), number of times when the EUS view of the needle was lost (P < 0.05), scope handling (P < 0.005), and skills rating (P < 0.001), whereas 4/5 (80 %) improved their number of attempts. The overall evaluation showed a significant decrease (P < 0.001) in the total time taken (11.2 ±â€Š7.8 vs 4.3 ±â€Š2.2 minutes), number of attempts (2.6 ±â€Š1.2 vs 1.2 ±â€Š0.7), number of times when the EUS view of the needle was lost (2.3 ±â€Š2 vs 0.5 ±â€Š0.7), and need for scope handling (1.1 ±â€Š1.7 vs 0.1 ±â€Š0.2). We also observed an improvement in skills rating (5 ±â€Š1.9 vs. 7.7 ±â€Š1.1). Conclusion: This newly designed ex-vivo model seems to be an effective way to improve the initial learning of EUS-FNA, by performing 30 procedures.

Evaluation of feasibility, efficiency and safety of a pure NOTES gastrojejunal bypass with gastric outlet obstruction, in an in vivo porcine model.

INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) gastrojejunal anastomosis (GJA) is a less invasive surgery for bariatric procedures and gastric outlet obstruction. The aim of this study was to evaluate the feasibility, efficacy, and safety of a pure NOTES gastrojejunal bypass using an in vivo porcine model. MATERIAL AND METHODS: A prospective study was performed on nine swine. A double-channel scope was used. The intervention steps were: (i) gastric incision; (ii) peritoneal access; (iii) jejunal loop selection and mobilization into the stomach; (iv) stoma creation within the gastric wall and incision; (v) anastomosis suture and pylorus closure using a T-tag prototype. The animals were assessed clinically for 3 weeks including the weight gain. The patency of the GJA was assessed at necropsy and a histological analysis was performed. RESULTS: We successfully performed all the procedures with a mean (standard deviation [SD]) operative time of 108 (26) minutes. We used a mean of 5.55 (1.30) stitches. There were no intraprocedural adverse events. Five animals survived up till euthanasia at 3 weeks (65 %). These showed a significant difference in weight curves of a loss of 3.2 kg compared with gain of 5.2 kg in a control group. Four pigs died from anastomotic dehiscence complicated by peritonitis. CONCLUSION: Gastrojejunal bypass with a pure NOTES approach is feasible. This procedure is effective, resulting in a patent anastomosis and a significant weight loss. However, the anastomotic dehiscence is a major concern because of its mortality rate, and further studies including improvement of the suturing device and the technique are needed.

64-Slice multidetector row CT angiography of the abdomen: comparison of low versus high concentration iodinated contrast media in a porcine model.

OBJECTIVE: In this study we aimed to assess the image quality and degree of vascular enhancement using low-concentration contrast media (LCCM) (300 mg I ml(-1)) and high-concentration contrast media (HCCM) (370 mg I ml(-1)) on 64-slice multidetector row CT (MDCT) abdominal CT angiography (CTA). In addition, we aimed to study the feasibility of using HCCM with a reduced total iodine dose. METHODS: CTA of the abdomen on a 64-slice MDCT was performed on 15 anaesthetised pigs. Study pigs were divided into three groups of five each based on the iodine concentration and dose received: Group A (LCCM; 300 mg I ml(-1)), Group B (HCCM; 370 mg I ml(-1)) and Group C HCCM with 20% less iodine dose. The total iodine injected was kept constant (600 mg kg(-1)) in Groups A and B. Qualitative and quantitative analyses were performed to study and compare each group for image quality, visibility of the branch order of the superior mesenteric artery (SMA), artefacts, degree of enhancement in the aorta and main stem arteries and uniformity of enhancement in the aorta. Groups were compared using the analysis of variance test. RESULTS: The image quality of 64-slice MDCT angiography was excellent with a mean score of 4.63 and confident visualisation of the third to fifth order branches of the SMA in all groups. Group B demonstrated superior vascular enhancement, as compared with Groups A and C (p≤0.05). Uniform aortic enhancement was achieved with the use of LCCM and HCCM with 20% less iodine dose. CONCLUSION: 64-slice MDCT angiography of the abdomen was of excellent quality. HCCM improves contrast enhancement and overall CTA image quality and allows the iodine dose to be reduced.

The compactEASIE is a feasible training model for endoscopic novices: a prospective randomised trial.

BACKGROUND: The objective benefit of a training using the compact Erlangen Active Simulator for Interventional Endoscopy-simulator was demonstrated in two prospective educational trials (New York, France). The present study analysed whether endoscopic novices are able to reach a comparable level of endoscopic skills as in the above-described projects. METHODS: Twenty-seven endoscopic novices (medical students, first year residents) were enrolled in this prospective, randomised trial. The compact Erlangen Active Simulator for Interventional Endoscopy-simulator with an upper GI-organ package and blood perfusion system was used as a training tool. Basic evaluation of endoscopic skills was performed after a practical and theoretical course in diagnostic upper GI endoscopy followed by a stratified randomisation according to the rating in endoscopic skills into intensive (n=14) and control group (n=13). The intensive group was trained 12 times every second week over 7 months in 4 endoscopic disciplines (manual skills, injection therapy, haemoclip, band ligation) by skilled endoscopist (three trainees/simulator). Assessment was performed (single steps/overall) using an analogue scale from 1 to 10 (1=worst, 10=optimal performance) by expert tutors. The control group was not trained. Blinded final evaluation of all participants was performed in January 2003. RESULTS: We observed in all techniques applied a significant improvement of endoscopic skills and of the performance time in the intensive group compared to the control group (p<0.001). The comparison with the previous projects showed that the intensively trained novices achieved comparable levels of performance to the GI fellows in the New York and France Project (at least 80% of the median score in three out of four techniques). CONCLUSION: Endoscopic novices acquired notable skills in interventional endoscopy in the simulator by an intensive, periodical training using the compactEASIE.

"Hemodynamic efficacy" of two endoscopic clip devices used in the treatment of bleeding vessels, tested in an experimental setting using the compact Erlangen Active Simulator for Interventional Endoscopy (compactEASIE) training model.

BACKGROUND AND STUDY AIMS: Hemoclip therapy is a well-established procedure in the treatment of gastrointestinal bleeding. Although new products are provided periodically by the industry, comparative investigations are lacking. We compared two different hemoclip devices in an experimental setting, assessing them using objective hemostatic parameters. MATERIALS AND METHODS: We compared two disposable clip devices (Olympus HX-200L-135 (n = 40) vs. Wilson-Cook Tri-Clip (n = 40)) in an experimental setting using the compact Erlangen Active Simulator for Interventional Endoscopy (compactEASIE) training model equipped with an upper gastrointestinal-organ package for bleeding simulation. This was a randomized, prospective, controlled trial. Four investigators with different levels of endoscopic experience applied ten hemoclip devices of each type to the spurting vessels, the clips allocated using a randomized list for each investigator. The efficacy of hemostasis was determined by continuous measurement of the pressure within the afferent vessel before and after clip application and calculation of the relative reduction of vessel diameter by the clip device. The system pressure was recorded over the period from 1 minute before to 1 minute after clip application. A secondary end point was a subjective assessment of the whole clip application procedure by the endoscopist and the assisting nurse, using a visual analog scale (0 - 100, with 100 representing the best experience). RESULTS: A total of 39/40 clips of each type were applied successfully. Both clip devices led to a significant increase in system pressure, representing significant relative reduction of vessel diameter (Olympus 5.4 +/- 7.5 %, p < 0.001; Cook 4.9 +/- 8.0 %, p < 0.001). Overall, there was no significant difference between the two devices ( P = 0.756). However, the investigator with the least experience in endoscopy (< 100 procedures) produced significantly inferior results compared with the other three investigators, who had performed between 2000 and 6000 procedures each ( P < 0.05). We found no evidence of a learning curve from the intra-observer results. The devices received good, but not significantly different, overall ratings by the endoscopists (Olympus 69 +/- 24 vs. Wilson-Cook 65 +/- 16) and by the assisting nurses (Olympus 77 +/- 9 vs. Wilson-Cook 70 +/- 22). CONCLUSIONS: Using an established cadaveric training model, no significant difference was found between the two types of hemoclip devices with respect to their "hemostatic efficacy". However, the experience of the endoscopist appears to play a major role in successful clip application. The use of a feedback mechanism in emergency endoscopy training, using continuous intravessel pressure monitoring, may substantially enhance the efficacy of training, resulting in a similar improvement in clinical results.

Objective benefit of a 1-day training course in endoscopic hemostasis using the "compactEASIE" endoscopy simulator.

BACKGROUND AND STUDY AIMS: The Erlangen Active Simulator for Interventional Endoscopy (EASIE) was introduced in 1997 as a training model for interventional endoscopy. Objective evidence of the benefits of training with this model has not previously been published. As part of two long-term projects, the benefits of a 1-day training course with the "compactEASIE" simulator were evaluated. MATERIALS AND METHODS: Fourteen American and 18 French gastroenterology fellows were enrolled. These fellows were participants in the intensive groups performing training in endoscopic hemostasis, with a total number of 28 fellows in New York and 36 in France. Gastrointestinal endoscopy faculty members in New York and France evaluated and timed the fellows in four disciplines to establish baseline skills (manual skills; injection and coagulation; Hemoclip application; and variceal ligation) with the compactEASIE simulator. The trainees were reevaluated after an intensive 1-day course (with two or three fellows and one instructor per station), also including preparation and assistance for each procedure. The assessment (overall and parts) was done by expert tutors using an ordinal scale ranging from 1 to 10 (1 = poorest, 10 = best), recording also mistakes and performance time. The compactEASIE simulator, equipped with an upper gastrointestinal organ package and an artificial blood perfusion system, was used as the training tool. RESULTS: A highly significant improvement ( P < or = 0.001) was observed in the performance of all endoscopic techniques. A significant reduction in performance time was also observed with three of the four endoscopic techniques. Successful hemostasis was significantly improved in two out of three techniques. CONCLUSIONS: A 1-day training course on endoscopic hemostasis using the compactEASIE simulator is capable of improving the performance of hemostasis procedures. Long-term effects of repeated training sessions are currently subject of collaborative studies in New York and France.

Feasibility of endoscopic ultrasound-guided portal vein embolization with Enteryx.

BACKGROUND: Portal vein embolization (PVE) has been used as a preoperative strategy to induce hepatic lobar atrophy and contralateral lobe hypertrophy. We determined the feasibility of endoscopic ultrasound (EUS)-guided Enteryx (EVAL/ethylene-vinyl alcohol copolymer) embolization of the portal vein (EUS-PVE) in an animal model as a potential, minimally invasive, endoscopic technique. METHODS: EUS-guided embolization of the portal vein (EUS-PVE) using Enteryx was performed in a Yorkshire breed swine. Portal pressure measurements were obtained before and after vascular embolization. The animal was carefully monitored for seven days for evidence of abdominal pain, shock, or bleeding. An upper abdominal contrast-CT scan was performed to verify the location of the embolus. RESULTS: The PV pressure increased from 3 mmHg at baseline to a mean of 15 mmHg after EUS-PVE. The CT-scan on day 4 demonstrated Enteryx in the main portal vein with extension into the left branch. At sacrifice on day 7, a solid thrombus was visible grossly and histologically inside the main portal vein and the left branch of the portal vein. CONCLUSIONS: Selective embolization of the portal vein by EUS guidance appears to be feasible and a potential, minimally invasive, preoperative treatment option for patients undergoing extensive hepatectomy.

Protein Z.

Protein Z is a vitamin K-dependent protein. The first cases of protein Z deficiency were described in patients suffering from a bleeding tendency from otherwise unknown origin. Today, diminutions of protein Z seem to play a role not only in bleeding patients but also in patients with factor V Leiden mutation: Patients presenting with factor V Leiden mutation and low protein Z levels show earlier onset and higher frequency of thromboembolic events than do patients presenting with factor V Leiden mutation and normal protein Z levels. Thus, protein Z is a good example for the--at first sight--paradox action of coagulation proteins.

[Visceral leishmaniasis with an unusually long incubation time]. / Viszerale Leishmaniose mit ungewöhnlich langer Inkubationszeit.

HISTORY: A 25-year-old woman of Yugoslavian origin came to Germany two years before and did not leave Germany since this time. She developed a phlebothrombosis during pregnancy which was treated surgically and with subsequent heparinisation. The pregnancy had to be terminated by section because of abnormal liver functions and increased blood pressure. These values returned to normal within two months. Further tests again showed raised liver function tests (GOT 57 U/l, GPT 71 U/l) and antibodies against smooth muscle and actin. Autoimmune hepatitis was diagnosed and prednisolone given (100 mg daily). In the subsequent 4 months the patient progressively lost more weight and a pancytopenia developed. Suspected of having a systemic haematological syndrome she was admitted to hospital. FINDINGS: Physical examination was unremarkable except for hepato- and splenomegaly (spleen 15.6 cm in diameter by sonography). Laboratory tests showed hypergammaglobulinaemia (50 g/l, 53%), increased WBC count, as well as decreased haemoglobin concentration and platelet count (900 WBC/microliter, Hb 10.9 g/l, 146,000 platelets/microliter). Bone marrow puncture unexpectedly revealed a large number of Leishmania donovani. TREATMENT AND COURSE: Five-valent antimony was administered (sodium stibogluconate 20 mg/kg daily intravenously as bolus for 14 days). She has been free of symptoms since then (follow-up period of one year). CONCLUSION: Visceral leishmaniasis is a rare disease in Europe. Incubation periods of several years have been reported and the infection can be easily mistaken for other chronic liver disease, in this case for an autoimmune hepatitis. Leishmaniasis should be included in the differential diagnosis of unclear liver disease if there is a suggestive history (country of origin or journey into an endemic area).

What the neurosurgeon needs to know about the coagulation system.

Intracranial surgery is often complicated by thromboembolic events including the life-threatening pulmonary embolism. After head trauma and in patients with brain tumors disseminated intravascular coagulation (DIC) can occur, characterized by the triggering of the coagulation cascade and the depletion of coagulation factors which ultimately leads to bleeding. The identification of patients at high risk as well as the early diagnosis of hemostatic problems uses routine laboratory parameters such as partial thromboplastin time and prothrombin time reflecting the intrinsic and the extrinsic pathway of the coagulation respectively. Thrombin antithrombin III complexes (TAT) and prothrombin fragment 1 + 2 (F1 + 2) are further indicators of an activation of the coagulation whereas fibrinogen degradation products (FDP) refer to the fibrinolytic system. The basic principles of coagulation and fibrinolysis are summarized as well as the changes of laboratory parameters accompanying DIC, hypercoagulability and hyperfibrinolysis.

Coagulation alterations in patients undergoing elective craniotomy.

BACKGROUND: Thromboembolism remains a major problem in patients scheduled for craniotomy. The present study examined parameters of coagulation and fibrinolysis in 15 patients undergoing elective craniotomy in the perioperative period. METHODS: Plasma concentrations of thrombin antithrombin III complex (TAT), prothrombin fragment 1 + 2 (F1 + 2), and d-dimer were measured before and after induction of anesthesia, 60 minutes and 180 minutes after the beginning of surgery, and on the first postoperative morning. RESULTS: TAT, a marker of activation of coagulation, increased significantly (p < 0.05) from the preoperative measurements to the data obtained 60 minutes after beginning the surgery, reaching a maximum of 180 minutes after the start of surgery. F1 + 2, also indicating activation, showed a similar concentration time course with an intraoperative maximum. D-dimer, a marker of fibrinolysis, tended to increase slightly beginning 180 minutes after surgery with a maximum on the morning after surgery. Statistical significance for F1 + 2 and d-dimer was not found. CONCLUSIONS: This study showed a transient activation of coagulation with an intraoperative maximum in patients undergoing craniotomy. This result could be due to a liberation of thromboplastin from brain tissue.

[The behavior of the activation parameters of plasma coagulation under HDR-afterloading therapy in patients with endometrial carcinoma]. / Verhalten der Aktivierungsparameter der plasmatischen Gerinnung unter HDR-Afterloading-Therapie bei Patientinnen mit Endometriumkarzinom.

BACKGROUND: In the radium era heparin prophylaxis was necessary to avoid thromboembolic events. Today with high-dose-rate (HDR) afterloading thromboembolic events are rare. Coagulation activation parameters were monitored during HDR afterloading to evaluate the necessity of heparin prophylaxis. PATIENTS AND METHODS: Twenty patients with uterine carcinoma and no postoperative tumor residuals were randomized before their first 10 Gy OD HDR-afterloading application. Ten patients received heparin prophylaxis, the other ten patients received no prophylaxis. Blood samples were taken before, immediately after, 6 and 24 hours after HDR afterloading. D-Dimer, TAT, and F 1 + 2 were measured. RESULTS: No significant activation of the coagulation system was observed over the investigated time period and no differences have been detected between both groups. None of the patients of either group developed thromboembolic complications. CONCLUSIONS: HDR afterloading has no direct influence on the plasmatic coagulation system. From this point of view heparin prophylaxis does not seem necessary.

[Endemic sprue: its first diagnosis based on bleeding complications]. / Einheimische Sprue: Erstdiagnose aufgrund von Blutungskomplikationen.

HISTORY AND CLINICAL FINDINGS: A 47-year-old man without previously known illness was admitted to hospital because of acute haematomas in the legs: the history revealed no cause. The pale-looking patient reported having large and foul-smelling stools once or twice daily. There were large haematomas and swellings on both legs. His general and nutritional state was reduced. "Bleeding of unknown origin" was suspected at this time. INVESTIGATIONS: Haemoglobin concentration was 5.6 g/dl, while iron was normal and ferritin reduced. Quick value was below 5%, activated partial thromboplastin time prolonged to 180 s. Vitamin A and E concentrations were reduced; coumarin derivatives were not demonstrated in blood. Abdominal ultrasonography showed clearly thickened intestinal walls. TREATMENT AND COURSE: Four units of erythrocyte concentrate were immediately administered, together with 2000 IU factors II, VII, X and anti-haemophilic factor B (PPSB), and 10 mg vitamin K intravenously. As intestinal malabsorption was suspected, a vitamin A absorption test was performed: it indicated malabsorption. Upper intestinal endoscopy showed coeliac disease, as did a biopsy. The patient's state quickly improved after he had been given vitamins A, D, E and K and put on a gluten-free diet. CONCLUSION: Coeliac disease can take a clinically unremarkable course for a long time and may finally become manifest through an isolated abnormality, such as bleeding.

Protein Z, a new haemostatic factor, in liver diseases.

Protein Z is a vitamin K-dependent plasma protein, which promotes the association of thrombin with phospholipid surfaces. Deficiency states of protein Z have recently been shown in patients with a bleeding tendency of an otherwise unknown origin. In the present study severe diminutions of blood plasma protein Z were found in patients with chronic liver diseases. Protein Z levels decreased with increasing severity of liver disease. Strong correlations between protein Z and other plasma proteins of liver origin indicate that protein Z primarily originates from the liver. The cutaneous bleeding tendency in cirrhosis may in part be due to protein Z deficiency.

Protein Z deficiency: a new cause of bleeding tendency.

Protein Z is a vitamin K-dependent plasma protein synthesized by the liver. Protein Z promotes the association of thrombin with phospholipid surfaces. So far, nothing is known about the clinical relevance of protein Z except alterations measured in patients under oral anticoagulant treatment. We propose that in protein Z deficiency a bleeding tendency might result because of the interaction of protein Z with thrombin on phospholipid endothelial surfaces. Therefore, we examined 36 patients with bleeding tendency of unknown origin, who were not under oral anticoagulant treatment and had normal liver synthesis function. Mean protein Z value of the patients with bleeding tendency was significantly diminished in comparison to the healthy control group. Twenty-one of the bleeding patients had lower protein Z levels than the lowest protein Z level of the control group. In conclusion, protein Z deficiency is described as a new type of bleeding tendency.

Coagulation activation in liver diseases.

In liver disorders alterations of the coagulation system are mainly due to a reduced synthesis of coagulation proteins. In addition, an enhanced intravascular consumption of coagulation factors is discussed controversely in liver diseases. By measuring factor IXiAT- and TAT-complexes we tried to find out, whether coagulation activation in liver patients leads to activation of the complete coagulation cascade followed by DIC or whether in some diseases a futile partial coagulation activation develops. In all liver diseases examined, elevated factor IXiAT-complexes were demonstrated, while TAT-complexes were only elevated in chronic active hepatitis, metabolic decompensated liver cirrhosis and in patients suffering from end stage liver disease. We conclude that all liver diseases examined lead to an activation of the coagulation cascade. A complete activation followed by DIC only occurs in patients with very severe liver disorders.