Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition.

Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting of the transcription factor MYC remains challenging. Here, we show that inhibition of the histone deacetylase 6 (HDAC6) using the HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic MYC levels and prevents lymphomagenesis in a mouse model of MYC-induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching the acetylation state of HDAC6 substrates, such as tubulin. Tubulin facilitates nuclear import of MYC, and MYC-dependent B-cell lymphoma cells rely on continuous import of MYC due to its high turn-over. Acetylation of tubulin impairs this mechanism and enables proteasomal degradation of MYC. M-100 targets almost exclusively B-cell lymphoma cells with high levels of MYC whereas non-tumor cells are not affected. M-100 induces massive apoptosis in human and murine MYC-overexpressing B-cell lymphoma cells. We identified the heat-shock protein DNAJA3 as an interactor of tubulin in an acetylation-dependent manner and overexpression of DNAJA3 resulted in a pronounced degradation of MYC. We propose a mechanism by which DNAJA3 associates with hyperacetylated tubulin in the cytoplasm to control MYC turnover. Taken together, our data demonstrate a beneficial role of HDAC6 inhibition in MYC-dependent B-cell lymphoma.

Radiation-Free Thoracic Endovascular Aneurysm Repair with Fiberoptic and Electromagnetic Guidance: A Phantom Study.

PURPOSE: To evaluate the feasibility and accuracy of a radiation-free implantation of a thoracic aortic stent graft employing fiberoptic and electromagnetic tracking in an anthropomorphic phantom. MATERIALS AND METHODS: An anthropomorphic phantom was manufactured based on computed tomography (CT) angiography data from a patient. An aortic stent graft application system was equipped with a fiber Bragg gratings and 3 electromagnetic sensors. The stent graft was navigated in the phantom by 3 interventionalists using the tracking data generated by both technologies. One implantation procedure was performed. The technical success of the procedure was evaluated using digital subtraction angiography and CT angiography (before and after the intervention). Tracking accuracy was determined at various anatomical landmarks based on separately acquired fluoroscopic images. The mean/maximum errors were measured for the stent graft application system and the tip/end of the stent graft. RESULTS: The procedure resulted in technical success with a mean error below 3 mm for the entire application system and <2 mm for the position of the tip of the stent graft. Navigation/implantation and handling of the device were rated sufficiently accurate and on par with comparable, routinely used stent graft application systems. CONCLUSIONS: The study demonstrates successful stent graft implantation during a thoracic endovascular aortic repair procedure employing advanced guidance techniques and avoiding fluoroscopic imaging. This is an essential step in facilitating the implantation of stent grafts and reducing the health risks associated with ionizing radiation during endovascular procedures.

Confocal laser microscopy without fluorescent dye in minimal-invasive thoracic surgery: an ex-vivo pilot study in lung cancer.

Cancer will be the leading cause of death in a few decades. In line with minimal invasive lung cancer surgery, surgeons loose most of their tactile tissue information and need an additional tool of intraoperative tissue navigation during surgery. Confocal laser microscopy is a well-established method of tissue investigation. In this ex-vivo pilot study, we evaluated an endoscopic confocal laser microscope (eCLM) that does not need any fluorescent dye as a diagnostic tool in non-malignant and malignant pulmonary tissue and distal stapler resection margins, respectively. In seven cases, an eCLM was used for examining pulmonary tissue ex-vivo. Images of non-malignant and non-small cell lung cancer tissue and distal stapler resection margins were characterized in terms of specific signal-patterns. No fluorescent dye was used. Correlations to findings in conventional histology were systematically recorded and described. Healthy lung tissue showed hyperreflectoric alveolar walls with dark alveolar spaces. Hyperreflective nets indicated the tumor stroma; whereas the hyperreflective areas indicated the tumor cell clusters. Compared to adenocarcinoma tissue, tissue from squamous cell carcinoma showed more distinctive hyperreflective stroma nets. eCLM characteristics seen in non-malignant and malignant tissue were also visible in distal stapler resection margins and so therefore it was feasible to distinguish between healthy lung tissue and lung cancer. This pilot study shows that the assessment of pulmonary tissue with this eCLM for minimally invasive surgical approach without any fluorescent dye is feasible. It enables to differentiate between benign and malignant tissue in pulmonary specimen by easy to evaluate and reproducible parameters.

Accuracy evaluation of patient-specific 3D-printed aortic anatomy.

INTRODUCTION: 3D printing has a wide range of applications in medicine. In surgery, this technique can be used for preoperative planning of complex procedures, production of patient specific implants, as well as training. However, accuracy evaluations of 3D vascular models are rare. OBJECTIVES: Aim of this study was to investigate the accuracy of patient-specific 3D-printed aortic anatomies. METHODS: Patients suffering from aorto-iliac aneurysms and with indication for treatment were selected on the basis of different anatomy and localization of the aneurysm in the period from January 1st 2014 to May 27th 2016. Six patients with aorto-iliac aneurysms were selected out of the database for 3D-printing. Subsequently, computed tomography (CT) images of the printed 3D-models were compared with the original CT data sets. RESULTS: The mean deviation of the six 3D-vascular models ranged between -0.73 mm and 0.14 mm compared to the original CT-data. The relative deviation of the measured values showed no significant difference between the 3D-vascular and the original patient CT-data. CONCLUSION: Our results showed that 3D printing has the potential to produce patient-specific 3D vascular models with reliable accuracy. This enables the use of such models for the development of new endovascular procedures and devices.

Clinical outcome of short-term compression after sclerotherapy for telangiectatic varicose veins.

BACKGROUND: Sclerotherapy is considered to be the method of choice for the treatment of telangiectatic varicose veins (C1 veins). Whereas the use of compression stockings after sclerotherapy is recommended, little is known about the impact of compression on the outcome of sclerotherapy. The aim of this study was to assess the influence of compression on the outcome of injection sclerotherapy of C1 varicose veins. METHODS: There were 100 legs of 50 consecutive patients with chronic venous insufficiency (C1) included. After randomization per patient, both legs were treated with sclerotherapy in a predefined area of the thigh (measuring 100 cm2), followed by eccentric compression for 24 hours. Group A received no further compression, whereas group B was additionally equipped with compression stockings of 18 to 20 mm Hg above the ankle and continued wearing these for 1 week. Photodocumentation was performed before, 1 week after, and 4 weeks after sclerotherapy, and the clinical outcome was assessed at these postprocedure follow-up dates. The photographs were reviewed by an internal unblinded rater and an independent blinded external rater. RESULTS: There was no discernible difference between the groups in terms of clinical outcome or side effects after 4 weeks. Whereas inter-rater reliability was high, there was no correlation between the raters and patients in terms of outcome. In 55% of the treated legs, the patients deemed the result of the treatment to be good; in 27% of the treated legs, fair; and in 18%, poor. Postprocedure hyperpigmentation occurred in 13% of patients and was comparable in both groups. Compression therapy was found to be comfortable by the majority (58%) of patients. CONCLUSIONS: One week of postinterventional compression therapy had no clinical benefit compared with no compression.

Three-dimensional guidance including shape sensing of a stentgraft system for endovascular aneurysm repair.

PURPOSE: During endovascular aneurysm repair (EVAR) procedures, medical instruments are guided with two-dimensional (2D) fluoroscopy and conventional digital subtraction angiography. However, this requires X-ray exposure and contrast agent is used, and the depth information is missing. To overcome these drawbacks, a three-dimensional (3D) guidance approach based on tracking systems is introduced and evaluated. METHODS: A multicore fiber with fiber Bragg gratings for shape sensing and three electromagnetic (EM) sensors for locating the shape were integrated into a stentgraft system. A model for obtaining the located shape of the first 38 cm of the stentgraft system with two EM sensors is introduced and compared with a method based on three EM sensors. Both methods were evaluated with a vessel phantom containing a 3D-printed vessel made of silicone and agar-agar simulating the surrounding tissue. RESULTS: The evaluation of the guidance methods resulted in average errors from 1.35 to 2.43 mm and maximum errors from 3.04 to 6.30 mm using three EM sensors, and average errors from 1.57 to 2.64 mm and maximum errors from 2.79 to 6.27 mm using two EM sensors. Moreover, the videos made from the continuous measurements showed that a real-time guidance is possible with both approaches. CONCLUSION: The results showed that an accurate real-time guidance with two and three EM sensors is possible and that two EM sensors are already sufficient. Thus, the introduced 3D guidance method is promising to use it as navigation tool in EVAR procedures. Future work will focus on developing a method with less EM sensors and a detailed latency evaluation of the guidance method.

[Laparoscopic Treatment of Splenic Artery Aneurysm]. / Laparoskopisches Ausschalten eines Aneurysmas der A. lienalis.

OBJECTIVE: Visceral artery aneurysms are a rare but dangerous vascular pathology. The branches of the coeliac trunc are most frequently affected, especially the splenic artery. A visceral aneurysm is usually diagnosed only when a bleeding complication occurs due to rupture. It is therefore recommended to treat this pathology at an early stage after diagnosis. Endovascular elimination is the preferred procedure. However, if endovascular elimination is not suitable, the visceral aneurysm can be successfully treated by minimally invasive surgery. INDICATIONS: Splenic artery aneurysms are located at the splenic hilum, and are therefore considered to be at high risk of splenic ischemia and secondary complications following endovascular coiling. PROCEDURE: Laparoscopic treatment of splenic artery aneurysm. CONCLUSION: In the case of complex vascular pathologies unsuitable for an endovascular approach, laparoscopic treatment of splenic artery aneurysm is a safe and effective minimally invasive option and alternative.

Special Section Guest Editorial: Translational Biophotonics.

This guest editorial introduces the special section on Translational Biophotonics.

Confocal laser microscopy as novel approach for real-time and in-vivo tissue examination during minimal-invasive surgery in colon cancer.

BACKGROUND: Histological analysis of surgical specimen is the gold standard for cancer classification. In particular, frozen histological diagnosis of vague peritoneal spots or uncertain excision of tumors plays a crucial role in the decision to proceed with or abandon an operation. Confocal laser microscopy (CLM) enables in-vivo and real-time high-resolution tissue analysis. This method has already been used during endoscopic assessments analyzing transformation of esophageal or colon mucosa. We examined whether a CLM device enables to distinguish between non-malignant and malignant tissue in vivo and real time and enables to assign peritoneal carcinomatosis spots to their primary tumor. In addition, we investigated whether the newly developed CLM camera device causes any tissue damage. METHODS: CC531 colon carcinoma cells were implanted on the serosa side of the colon and intraperitoneally in Wag/Rija rats via laparotomy. After 7 days of tumor growth, confocal laser microscopy in vivo was performed by re-laparotomy. Images of non-malignant and malignant tissue were characterized in terms of specific signal pattern. No fluorescent dye was used. Correlations to findings in conventional histology were systematically recorded and described. Potential tissue damage was examined by conventional histology. RESULTS: All animals survived the operative procedure and could be evaluated 7 days following surgery. No unexpected death occurred after surgery. Non-malignant colon is defined by small cycles of the microvilli of the colon. There is repetitive deregulated structure in colon carcinoma. Peritoneal carcinomatosis showed the same structural pattern as in primary colon carcinoma. In all examined cases, it was possible to differentiate between peritoneal carcinomatosis spots and non-malignant peritoneum. The CLM device did not cause any tissue damage. CONCLUSIONS: The CLM camera device reported here is feasible to identify peritoneal carcinomatosis spots, assign these spots to the primary tumor, as well as distinguish between non-malignant and malignant tissue in without using any fluorescent dye.

Analysis of laparoscopic laser liver resection in standardized porcine model.

BACKGROUND: Hepatocellular carcinoma is a highly prevalent and lethal primary neoplasia of the liver and metastases of other malignancies affect most frequently the liver. Minimally invasive surgical approach for liver resections is advancing. Dissection of liver parenchyma by laparoscopic technique remains challenging and new technologies are in need. Therefore, we asked whether it is feasible to dissect liver tissue comparably in terms of speed and hemostasis with a non-contact 1.9-µm cw-laser device and whether there are differences in the postoperative healing process compared to a gold standard device (ultrasound aspirator) in an experimental model. METHODS: Laparoscopic laser and ultrasound aspirator standardized partial liver resections were performed in seven pigs. Resection time, hemostasis time, and blood loss were evaluated. After at least 10 days, representative specimen of the resection areas was collected via re-laparoscopy and biopsy and side effects like hematoma, abscess, or bilioma were noted. Histologically, coagulation necrosis margin, granulation tissue zone, tissue fibrosis, and giant cell count were analyzed. RESULTS: Laparoscopic laser liver resection was three times faster compared to the laparoscopic ultrasound aspirator. Blood loss was equal in both groups. No side effects like hematoma or bilioma occurred. Histologically, specimen showed the same expansion of coagulation necrosis zone and granulation tissue. Fibrotic scar could be determined in three cases in both groups, respectively. However, giant cell count was significant higher in the laser resection group. CONCLUSIONS: The 1.9-µm cw-laser device enables a safe and fast liver resection in an experimental pig model compared to a gold standard (ultrasound aspirator) laparoscopic liver resection method. Wound healing is not interfered by laser liver resection.

Initial experience with the E-ventus® stent-graft for endovascular treatment of visceral artery aneurysms.

BACKGROUND: To evaluate the safety and efficacy of a novel balloon-expandable stent-graft for endovascular treatment of visceral artery aneurysms (VAA). METHODS: Between 9/2014 and 1/2017 seven patients (69±15 years) with true (N.=4) and false (N.=3) VAAs were treated by implantation of balloon-expandable stent-grafts (E-ventus®, Jotec, Hechingen, Germany) using a transfemoral (N.=2) or transbrachial (N.=5) vascular access. The stent-graft was placed without prior passing of the landing zone with a sheath. In 3 of 7 patients (42.9%) additional coil or plug embolization was performed to prevent retrograde VAA perfusion. Endpoints were technical success (defined as delivery and implantation of the stent-graft in the intended position with complete exclusion of the VAA), peri-procedural complications and patency. RESULTS: Mean diameters of true VAAs (splenic artery: N.=2, common hepatic artery: N.=1, celiac trunk: N.=1) were 26±9 and of false (common hepatic artery: N.=2, gastroduodenal artery: N.=1) 29±14 mm. False aneurysms presented as emergencies with active bleeding. Technical success was 100%. One peri-procedural complication was noted: pseudoaneurysm of the accessed brachial artery. After a mean follow-up of 187 days 6/7 stent-grafts (85.7%) were patent. One patient (fVAA) died two days after the emergency procedure owing to multi-organ failure which was assessed to be non-procedure-related. Another patient (fVAA) died 7 months from the procedure owing to cancer. CONCLUSIONS: Endovascular treatment of true and false visceral artery aneurysms by use of the E-ventus® stent-graft is safe and effective. Flexibility of the stent-graft and shaft allows for implantation without passing the lesion with a sheath, enabling treatment of distal as well as complex visceral lesions. Long-term results regarding patency in a larger patient cohort are needed to confirm these findings.

Navigation and visualisation with HoloLens in endovascular aortic repair.

INTRODUCTION: Endovascular aortic repair (EVAR) is a minimal-invasive technique that prevents life-threatening rupture in patients with aortic pathologies by implantation of an endoluminal stent graft. During the endovascular procedure, device navigation is currently performed by fluoroscopy in combination with digital subtraction angiography. This study presents the current iterative process of biomedical engineering within the disruptive interdisciplinary project Nav EVAR, which includes advanced navigation, image techniques and augmented reality with the aim of reducing side effects (namely radiation exposure and contrast agent administration) and optimising visualisation during EVAR procedures. This article describes the current prototype developed in this project and the experiments conducted to evaluate it. METHODS: The current approach of the Nav EVAR project is guiding EVAR interventions in real-time with an electromagnetic tracking system after attaching a sensor on the catheter tip and displaying this information on Microsoft HoloLens glasses. This augmented reality technology enables the visualisation of virtual objects superimposed on the real environment. These virtual objects include three-dimensional (3D) objects (namely 3D models of the skin and vascular structures) and two-dimensional (2D) objects [namely orthogonal views of computed tomography (CT) angiograms, 2D images of 3D vascular models, and 2D images of a new virtual angioscopy whose appearance of the vessel wall follows that shown in ex vivo and in vivo angioscopies]. Specific external markers were designed to be used as landmarks in the registration process to map the tracking data and radiological data into a common space. In addition, the use of real-time 3D ultrasound (US) is also under evaluation in the Nav EVAR project for guiding endovascular tools and updating navigation with intraoperative imaging. US volumes are streamed from the US system to HoloLens and visualised at a certain distance from the probe by tracking augmented reality markers. A human model torso that includes a 3D printed patient-specific aortic model was built to provide a realistic test environment for evaluation of technical components in the Nav EVAR project. The solutions presented in this study were tested by using an US training model and the aortic-aneurysm phantom. RESULTS: During the navigation of the catheter tip in the US training model, the 3D models of the phantom surface and vessels were visualised on HoloLens. In addition, a virtual angioscopy was also built from a CT scan of the aortic-aneurysm phantom. The external markers designed for this study were visible in the CT scan and the electromagnetically tracked pointer fitted in each marker hole. US volumes of the US training model were sent from the US system to HoloLens in order to display them, showing a latency of 259±86 ms (mean±standard deviation). CONCLUSION: The Nav EVAR project tackles the problem of radiation exposure and contrast agent administration during EVAR interventions by using a multidisciplinary approach to guide the endovascular tools. Its current state presents several limitations such as the rigid alignment between preoperative data and the simulated patient. Nevertheless, the techniques shown in this study in combination with fibre Bragg gratings and optical coherence tomography are a promising approach to overcome the problems of EVAR interventions.

Laparoscopic Confocal Laser Microscopy Without Fluorescent Injection: A Pilot Ex Vivo Study in Colon Cancer.

Introduction Histological analysis of surgical specimen is the gold standard for cancer classification. In particular, frozen histological diagnosis of vague peritoneal spots or uncertain excision of tumors plays a crucial role for proceeding with or without change of the operation procedure. Confocal laser microscopy (CLM) enables in vivo and real-time high-resolution tissue analysis. To evaluate a novel technique of CLM without any fluorescent dye, this pilot ex vivo study demonstrates a CLM camera device for minimal invasive surgical approach. Methods In 5 cases, a laparoscopic CLM camera was used for examining colon and rectum specimen. Images of nonmalignant and malignant intestinal mucosa were characterized in terms of specific signal-patterns. No fluorescent dye was used. Correlations to findings in conventional histology were systematically recorded and described. Results Using this CLM camera device, it is possible to analyze colon specimen mucosa. Nonmalignant and malignant intestinal mucosa show specific signal patterns. Nonmalignant mucosa is defined by honeycomb structure. There is deregulated structure in colon and rectum carcinoma mucosa. The inside lumen is irregular. The radial border appears swollen with reduced contrast. Discussion This pilot study shows that the assessment of colon mucosa with a prototype of CLM camera for minimally invasive surgical approach without any fluorescent dye is feasible. It is possible to differentiate between benign and malignant mucosa in colon specimen by easy to evaluate and reproducible parameters. These first steps of this pioneering achievement to establish CLM in minimal invasive surgical procedures show a great potential for a more reliable intraoperative evaluation of suspect foci.

Survival of diabetes patients with major amputation is comparable to malignant disease.

INTRODUCTION: Almost all studies on diabetic foot syndrome focused on prevention of amputation and did not investigate long-term prognosis and survival of patients as a primary outcome parameter. METHODS: We did a retrospective cohort study including 314 patients who had diabetic foot syndrome and underwent amputation between December 1995 and January 2001. RESULTS: A total of 48% of patients received minor amputation (group I), 15% only major amputation (group II) and 36% initially underwent a minor amputation that was followed by a major amputation (group III). Statistically significant differences were observed in comparison of the median survival of group I to group II (51 vs. 40 months; p = 0.016) and of group II to group III (40 vs. 55 months; p = 0.003). DISCUSSION: The prognosis of patients with major amputation due to diabetic foot syndrome is comparable to patients with malignant diseases. Vascular interventions did not improve the individual prognosis of patients.

The "buddy balloon technique" facilitates retrograde ipsilateral access to postdilate an iliac side branch after endovascular aneurysm repair.

If unilateral common iliac aneurysms occur simultaneously with abdominal aortic aneurysm, endovascular treatment consists of implantation of a bifurcated stent graft with extension into the external iliac artery while the ipsilateral internal iliac artery is often occluded. The internal iliac artery may be preserved by an iliac branch device (IBD). In this technical note, we describe a technique to probe the side branch of an IBD for postdilation through an ipsilateral retrograde access using one balloon to block the way upstream while directing a second percutaneous transluminal angioplasty balloon into the side branch despite the hostile angle of side branch and IBD.

Ultrasound-based tumor movement compensation during navigated laparoscopic liver interventions.

BACKGROUND: Image-guided navigation aims to provide better orientation and accuracy in laparoscopic interventions. However, the ability of the navigation system to reflect anatomical changes and maintain high accuracy during the procedure is crucial. This is particularly challenging in soft organs such as the liver, where surgical manipulation causes significant tumor movements. We propose a fast approach to obtain an accurate estimation of the tumor position throughout the procedure. METHODS: Initially, a three-dimensional (3D) ultrasound image is reconstructed and the tumor is segmented. During surgery, the position of the tumor is updated based on newly acquired tracked ultrasound images. The initial segmentation of the tumor is used to automatically detect the tumor and update its position in the navigation system. Two experiments were conducted. First, a controlled phantom motion using a robot was performed to validate the tracking accuracy. Second, a needle navigation scenario based on pseudotumors injected into ex vivo porcine liver was studied. RESULT: In the robot-based evaluation, the approach estimated the target location with an accuracy of 0.4 ± 0.3 mm. The mean navigation error in the needle experiment was 1.2 ± 0.6 mm, and the algorithm compensated for tumor shifts up to 38 mm in an average time of 1 s. CONCLUSION: We demonstrated a navigation approach based on tracked laparoscopic ultrasound (LUS), and focused on the neighborhood of the tumor. Our experimental results indicate that this approach can be used to quickly and accurately compensate for tumor movements caused by surgical manipulation during laparoscopic interventions. The proposed approach has the advantage of being based on the routinely used LUS; however, it upgrades its functionality to estimate the tumor position in 3D. Hence, the approach is repeatable throughout surgery, and enables high navigation accuracy to be maintained.

Prospective Analysis of More than 1,000 Patients with Rectal Carcinoma: Are There Gender-Related Differences?

BACKGROUND: Since the beginning of the new millennium gender medicine has become more and more relevant. The goal has been to unveil differences in presentation, treatment response, and prognosis of men and women with regard to various diseases. METHODS: This study encompassed 1,061 patients who underwent surgery for rectal cancer at the Department of Surgery, University Medical Center Schleswig-Holstein Campus Lübeck, Germany, between January 1990 and December 2011. Prospectively documented demographic, clinical, pathological, and follow-up data were obtained. Analysis encompassed the comparison of clinical, histopathological, and oncological parameters with regard to the subcohorts of male and female patients. RESULTS: No statistically significant differences could be found for clinical and histopathological parameters, location of tumor, resection with or without anastomosis, palliative or curative treatment, conversion rates, duration of surgery, and long-term survival. For the entire cohort, gender-related statistically significant differences in complications encompassed anastomotic leakage, burst abdomen, pneumonia, and urinary tract complications all of which occurred more often in men. CONCLUSION: Data obtained in this study suggest that there are no gender-related differences in the oncologic surgical treatment of patients with rectal carcinoma. However, male sex seems to be a risk factor for increased early postoperative morbidity.

Aneuploidy and elevated CEA indicate an increased risk for metachronous metastasis in colorectal cancer.

PURPOSE: Presently, no markers exist to predict metachronous metastasis at the time a primary colorectal cancer is diagnosed. While aneuploidy indicates poor survival prognosis and elevated carcinoembryonic antigen (CEA) levels the presence of recurrent disease, the predictive value of both markers regarding imminent metachronous metastases is unclear. METHODS: Sixty patients with distant recurrence throughout a 5-year follow-up (TM+) were randomly chosen and 60 patients without metastasis matched to this cohort (TM-). In addition, an enlarged collective (n = 217; n TM+ = 85, n TM- = 132) with median follow-up of 79.2 months was assessed by logistic regression regarding metachronous metastases. Univariate and stepwise regression analyses included clinicopathological characteristics, preoperative CEA levels and aneuploidy assessed by DNA image cytometry. RESULTS: The matched-pair collective showed aneuploidy in 71.1 % (TM-) and 85.0 % (TM+; p = 0.076), and elevated CEA in 24.5 % (TM-) and 52.2 % [TM+; odds ratio (OR), 3.414; p = 0.007]. The enlarged collective presented aneuploidy in 71.2 % (TM-) and 83.5 % (TM+; OR 2.050, p = 0.038), and elevated CEA in 28.6 % (TM-) and 48.9 % (TM+; OR 2.391, p = 0.020). Elevated CEA and aneuploidy did not show any association (p = 0.919). In contrast, logistic regression analyses demonstrated that besides increased T category (OR 1.745, p = 0.019), both elevated CEA level (OR 2.633, p = 0.015) and aneuploidy (OR 1.929, p = 0.058) were independent predictive markers for metachronous metastasis. CONCLUSIONS: Our data show that aneuploidy and elevated CEA levels besides increased T category could serve for individual risk assessment to predict metachronous metastases. The fact that still aneuploidy missed the significance level by a small margin emphasizes the need for larger validation studies.

Laparoscopic navigated liver resection: technical aspects and clinical practice in benign liver tumors.

Laparoscopic liver resection has been performed mostly in centers with an extended expertise in both hepatobiliary and laparoscopic surgery and only in highly selected patients. In order to overcome the obstacles of this technique through improved intraoperative visualization we developed a laparoscopic navigation system (LapAssistent) to register pre-operatively reconstructed three-dimensional CT or MRI scans within the intra-operative field. After experimental development of the navigation system, we commenced with the clinical use of navigation-assisted laparoscopic liver surgery in January 2010. In this paper we report the technical aspects of the navigation system and the clinical use in one patient with a large benign adenoma. Preoperative planning data were calculated by Fraunhofer MeVis Bremen, Germany. After calibration of the system including camera, laparoscopic instruments, and the intraoperative ultrasound scanner we registered the surface of the liver. Applying the navigated ultrasound the preoperatively planned resection plane was then overlain with the patient's liver. The laparoscopic navigation system could be used under sterile conditions and it was possible to register and visualize the preoperatively planned resection plane. These first results now have to be validated and certified in a larger patient collective. A nationwide prospective multicenter study (ProNavic I) has been conducted and launched.

Metachronous metastasis- and survival-analysis show prognostic importance of lymphadenectomy for colon carcinomas.

BACKGROUND: Lymphadenectomy is performed to assess patient prognosis and to prevent metastasizing. Recently, it was questioned whether lymph node metastases were capable of metastasizing and therefore, if lymphadenectomy was still adequate. We evaluated whether the nodal status impacts on the occurrence of distant metastases by analyzing a highly selected cohort of colon cancer patients. METHODS: 1,395 patients underwent surgery exclusively for colon cancer at the University of Lübeck between 01/1993 and 12/2008. The following exclusion criteria were applied: synchronous metastasis, R1-resection, prior/synchronous second carcinoma, age < 50 years, positive family history, inflammatory bowel disease, FAP, HNPCC, and follow-up < 5 years. The remaining 421 patients were divided into groups with (TM+, n = 75) or without (TM-, n = 346) the occurrence of metastasis throughout a 5-year follow-up. RESULTS: Five-year survival rates for TM + and TM- were 21% and 73%, respectively (p < 0.0001). Survival rates differed significantly for N0 vs. N2, grading 2 vs. 3, UICC-I vs. -II and UICC-I vs. -III (p < 0.05). Regression analysis revealed higher age upon diagnosis, increasing N- and increasing T-category to significantly impact on recurrence free survival while increasing N-and T-category were significant parameters for the risk to develop metastases within 5-years after surgery (HR 1.97 and 1.78; p < 0.0001). CONCLUSIONS: Besides a higher T-category, a positive N-stage independently implies a higher probability to develop distant metastases and correlates with poor survival. Our data thus show a prognostic relevance of lymphadenectomy which should therefore be retained until conclusive studies suggest the unimportance of lmyphadenectomy.