A surgical activity model of laparoscopic cholecystectomy for co-operation with collaborative robots.

BACKGROUND: Laparoscopic cholecystectomy is a very frequent surgical procedure. However, in an ageing society, less surgical staff will need to perform surgery on patients. Collaborative surgical robots (cobots) could address surgical staff shortages and workload. To achieve context-awareness for surgeon-robot collaboration, the intraoperative action workflow recognition is a key challenge. METHODS: A surgical process model was developed for intraoperative surgical activities including actor, instrument, action and target in laparoscopic cholecystectomy (excluding camera guidance). These activities, as well as instrument presence and surgical phases were annotated in videos of laparoscopic cholecystectomy performed on human patients (n = 10) and on explanted porcine livers (n = 10). The machine learning algorithm Distilled-Swin was trained on our own annotated dataset and the CholecT45 dataset. The validation of the model was conducted using a fivefold cross-validation approach. RESULTS: In total, 22,351 activities were annotated with a cumulative duration of 24.9 h of video segments. The machine learning algorithm trained and validated on our own dataset scored a mean average precision (mAP) of 25.7% and a top K = 5 accuracy of 85.3%. With training and validation on our dataset and CholecT45, the algorithm scored a mAP of 37.9%. CONCLUSIONS: An activity model was developed and applied for the fine-granular annotation of laparoscopic cholecystectomies in two surgical settings. A machine recognition algorithm trained on our own annotated dataset and CholecT45 achieved a higher performance than training only on CholecT45 and can recognize frequently occurring activities well, but not infrequent activities. The analysis of an annotated dataset allowed for the quantification of the potential of collaborative surgical robots to address the workload of surgical staff. If collaborative surgical robots could grasp and hold tissue, up to 83.5% of the assistant's tissue interacting tasks (i.e. excluding camera guidance) could be performed by robots.

Ensuring privacy protection in the era of big laparoscopic video data: development and validation of an inside outside discrimination algorithm (IODA).

BACKGROUND: Laparoscopic videos are increasingly being used for surgical artificial intelligence (AI) and big data analysis. The purpose of this study was to ensure data privacy in video recordings of laparoscopic surgery by censoring extraabdominal parts. An inside-outside-discrimination algorithm (IODA) was developed to ensure privacy protection while maximizing the remaining video data. METHODS: IODAs neural network architecture was based on a pretrained AlexNet augmented with a long-short-term-memory. The data set for algorithm training and testing contained a total of 100 laparoscopic surgery videos of 23 different operations with a total video length of 207 h (124 min ± 100 min per video) resulting in 18,507,217 frames (185,965 ± 149,718 frames per video). Each video frame was tagged either as abdominal cavity, trocar, operation site, outside for cleaning, or translucent trocar. For algorithm testing, a stratified fivefold cross-validation was used. RESULTS: The distribution of annotated classes were abdominal cavity 81.39%, trocar 1.39%, outside operation site 16.07%, outside for cleaning 1.08%, and translucent trocar 0.07%. Algorithm training on binary or all five classes showed similar excellent results for classifying outside frames with a mean F1-score of 0.96 ± 0.01 and 0.97 ± 0.01, sensitivity of 0.97 ± 0.02 and 0.0.97 ± 0.01, and a false positive rate of 0.99 ± 0.01 and 0.99 ± 0.01, respectively. CONCLUSION: IODA is able to discriminate between inside and outside with a high certainty. In particular, only a few outside frames are misclassified as inside and therefore at risk for privacy breach. The anonymized videos can be used for multi-centric development of surgical AI, quality management or educational purposes. In contrast to expensive commercial solutions, IODA is made open source and can be improved by the scientific community.

Analysis of predictors for postoperative complications after pancreatectomy--what is new after establishing the definition of postpancreatectomy acute pancreatitis (PPAP)?

PURPOSE: We aimed to analyze the predictive value of hyperamylasemia after pancreatectomy for morbidity and for the decision to perform rescue completion pancreatectomy (CP) in a retrospective cohort study. METHODS: Data were extracted from a retrospective clinical database. Postoperative hyperamylasemia (POH) and postoperative hyperlipasemia (POHL) were defined by values greater than those accepted as the upper limit at our institution on postoperative day 1 (POD1). The endpoints of the study were the association of POH with postoperative morbidity and the possible predictors for postpancreatectomy acute pancreatitis (PPAP) and severe complications such as the necessity for rescue CP. RESULTS: We analyzed 437 patients who underwent pancreaticoduodenectomy over a period of 7 years. Among them, 219 (52.3%) patients had POH and 200 (47.7%) had normal postoperative amylase (non-POH) levels. A soft pancreatic texture (odds ratio [OR] 3.86) and POH on POD1 (OR 8.2) were independent predictors of postoperative pancreatic fistula (POPF), and POH on POD1 (OR 6.38) was an independent predictor of rescue CP. The clinically relevant POPF (49.5% vs. 11.4%, p < 0.001), intraabdominal abscess (38.3% vs. 15.3%, p < 0.001), postoperative hemorrhage (22.8% vs. 5.1%, p < 0.001), major complications (Clavien-Dindo classification > 2) (52.5% vs. 25.6%, p < 0.001), and CP (13% vs. 1.8%, p < 0.001) occurred significantly more often in the POH group than in the non-POH group. CONCLUSION: Although POH on POD1 occurs frequently, in addition to other risk factors, it has a predictive value for the development of postoperative morbidity associated with PPAP and CP.

How we do it-the use of peritoneal patches for reconstruction of vena cava inferior and portal vein in hepatopancreatobiliary surgery.

PURPOSE: Extended resections in hepatopancreatobiliary (HPB) surgery frequently require vascular resection to obtain tumor clearance. The use of alloplastic grafts may increase postoperative morbidity due to septic or thrombotic complications. The use of suitable autologous venous interponates (internal jugular vein, great saphenous vein) is frequently associated with additional incisions. The aim of this study was to report on our experience with venous reconstruction using the introperative easily available parietal peritoneum, focusing on key technical aspects. METHODS: All patients who underwent HPB resections with venous reconstruction using peritoneal patches at our department between January 2017 and November 2021 were included in this retrospective analysis with median follow-up of 2 months (IQR: 1-8 months). We focused on technical aspects of the procedure and evaluated vascular patency and perioperative morbidity. RESULTS: Parietal peritoneum patches (PPPs) were applied for reconstruction of the inferior vena cava (IVC) (13 patients) and portal vein (PV) (4 patients) during major hepatic (n = 14) or pancreatic (n = 2) resections. There were no cases of postoperative bleeding due to anastomotic leakage. Following PV reconstruction, two patients showed postoperative vascular stenosis after severe pancreatitis with postoperative pancreatic fistula and bile leakage, respectively. In patients with reconstruction of the IVC, no relevant perioperative vascular complications occurred. CONCLUSIONS: The use of a peritoneal patch for reconstruction of the IVC in HPB surgery is a feasible, effective, and low-cost alternative to alloplastic, xenogenous, or venous grafts. The graft can be easily harvested and tailored to the required size. More evidence is still needed to confirm the safety of this procedure for the portal vein regarding long-term results.

Short-term preoperative drainage is associated with improved postoperative outcomes compared to that of long-term biliary drainage in pancreatic surgery.

PURPOSE: The treatment of choice for patients presenting with obstructive cholestasis due to periampullary carcinoma is oncologic resection without preoperative biliary drainage (PBD). However, resection without PBD becomes virtually impossible in patients with obstructive cholangitis or severely impaired liver cell function. The appropriate duration of drainage by PBD has not yet been defined for these patients. METHODS: A retrospective analysis was conducted on 170 patients scheduled for pancreatic resection following biliary drainage between January 2012 and June 2018 at the University Hospital Dresden in Germany. All patients were deemed eligible for inclusion, regardless of the underlying disease entity. The primary endpoint analysis was defined as the overall morbidity (according to the Clavien-Dindo classification). Secondary endpoints were the in-hospital mortality and malignancy adjusted overall and recurrence-free survival rates. RESULTS: A total of 170 patients were included, of which 45 (26.5%) and 125 (73.5%) were assigned to the short-term (< 4 weeks) and long-term (≥ 4 weeks) preoperative drainage groups, respectively. Surgical complications (Clavien-Dindo classification > 2) occurred in 80 (47.1%) patients, with significantly fewer complications observed in the short-term drainage group (31.1% vs. 52%; p = 0.02). We found that long-term preoperative drainage (unadjusted OR, 3.386; 95% CI, 1.507-7.606; p < 0.01) and periampullary carcinoma (unadjusted OR, 5.519; 95% CI, 1.722-17.685; p-value < 0.01) were independent risk factors for postoperative morbidity, based on the results of a multivariate regression model. The adjusted overall and recurrence-free survival did not differ between the groups (p = 0.12). CONCLUSION: PBD in patients scheduled for pancreatic surgery is associated with substantial perioperative morbidity. Our results indicate that patients who have undergone PBD should be operated on within 4 weeks after drainage.

Influence of Molecular Status on Recurrence Site in Patients Treated for a Stage III Colon Cancer: a Post Hoc Analysis of the PETACC-8 Trial.

BACKGROUND: Recurrence patterns in stage III colon cancer (CC) patients according to molecular markers remain unclear. The objective of the study was to assess recurrence patterns according to microsatellite instability (MSI), RAS and BRAFV600E status in stage III CC patients. METHODS: All stage III CC patients from the PETACC-8 randomized trial tested for MSI, RAS and BRAFV600E status were included. The site and characteristics of recurrence were analyzed according to molecular status. Survival after recurrence (SAR) was analyzed. RESULTS: A total of 1650 patients were included. Recurrence occurred in 434 patients (26.3%). Microsatellite stable (MSS) patients had a significantly higher recurrence rate (27.2% vs. 18.7%, P = 0.02) with a trend to more pulmonary recurrence (28.8% vs. 12.9%, P = 0.06) when compared to MSI patients. MSI patients experienced more regional lymph nodes compared to MSS (12.9% vs. 4%, P = 0.046). In the MSS population, the recurrence rate was significantly higher in RAS (32.2%) or BRAF (32.3%) patients when compared to double wild-type patients (19.9%) (p < 0.001); no preferential site of recurrence was observed according to RAS and BRAFV600E mutations. Finally, decreased SAR was observed in the case of peritoneal recurrence or more than two recurrence sites. CONCLUSIONS: Microsatellite, RAS and BRAFV600E status influences recurrence rates in stage III CC patients. However, only microsatellite status seems to be associated with specific recurrence patterns. More than two recurrence sites and recurrence in the peritoneum were associated with poorer SAR.

Randomized clinical trial of stapler hepatectomy versus LigaSure™ transection in elective hepatic resection.

BACKGROUND: Previous studies have demonstrated stapler hepatectomy and use of various energy devices to be safe alternatives to the clamp-crushing technique in elective hepatic resection. In this randomized trial, the effectiveness and safety of stapler hepatectomy were compared with those of parenchymal transection with the LigaSure™ vessel sealing system. METHOD: Patients scheduled for elective liver resection at two tertiary-care centres were randomized during surgery to stapler hepatectomy or transection with the LigaSure™ device. Total intraoperative blood loss was the primary efficacy endpoint. Transection time, duration of operation, perioperative complications and length of hospital stay were recorded as secondary endpoints. RESULTS: A total of 138 patients were analysed, 69 in the LigaSure™ and 69 in the stapler hepatectomy group. Baseline characteristics were well balanced between the groups. Mean intraoperative blood loss was significantly higher in the LigaSure™ group than the stapler hepatectomy group: 1101 (95 per cent c.i. 915 to 1287) versus 961 (752 to 1170) ml (P = 0·028). The parenchymal transection time was significantly shorter in the stapler group (P = 0·005), as was the total duration of operation (P = 0·027). Surgical morbidity did not differ between the groups, nor did the grade of complications. CONCLUSION: Stapler hepatectomy was associated with reduced blood loss and a shorter duration of operation than the LigaSure™ device for parenchymal transection in elective partial hepatectomy. Registration number: NCT01858987 (http://www.clinicaltrials.gov).

KidsBrainIT: A New Multi-centre, Multi-disciplinary, Multi-national Paediatric Brain Monitoring Collaboration.

OBJECTIVES: Validated optimal cerebral perfusion pressure (CPP) treatment thresholds in children do not exist. To improve the intensive care unit (ICU) management of the paediatric traumatic brain injury (TBI) population, we are forming a new paediatric multi-centre collaboration to recruit standardised ICU data for running and reporting upon models for assessing autoregulation and optimal CCP (CPPopt). MATERIALS AND METHODS: We are adapting the adult BrainIT group's approach to develop a new Paediatric Brain Monitoring and Information Technology Group (KidsBrainIT), which will include a repository to store prospectively collected high-resolution physiological, clinical, and outcome data. In the first phase of this project there are 7 UK Paediatric Intensive Care Units, 1 Spanish, 1 Belgium, and 1 Romanian Centre interested in participating. In subsequent phases, we plan to open recruitment to other centres both within Europe, US and abroad. We are collaborating with the Leuven Group and plan to use their LAx (low-frequency autoregulation index), DATACAR (dynamic adaptive target of active cerebral autoregulation), CPPopt and visualisation methodologies. We also plan to use the continuous diffuse optical monitoring and tomography technology developed in Barcelona as an acute surrogate end-point for optimising brain perfusion. This technology allows non-invasive continuous monitoring of deep tissue perfusion and oxygenation in adults but its clinical application in infants and children with TBI has not been studied previously. RESULTS: We report on the current status of setting up this new collaboration and also on pilot analyses in two centres which are the basis of our rationale for the need for a prospective validation study of CPPopt in children. Specifically, we demonstrated that CPPopt varied with time for each patient during their paediatric intensive care unit (PICU) stay, and the median overall CPPopt levels for children aged 2-6 years, 7-11 years and 12-16 years were 68.83, 68.09, and 72.17 mmHg respectively. Among survivors and patients with favourable outcome (GOS 4 and 5), there were significantly higher proportions with CPP monitoring time within CPPopt (p = 0.04 and p = 0.01 respectively). CONCLUSIONS: There is a need and an interest in forming a multi-centre PICU collaboration for acquiring data and performing analyses for determining validated CPPopt thresholds in the paediatric TBI population. KidsBrainIT is being formed to meet that need.

Management of patients with pancreatic cystic lesions: A case-based survey.

BACKGROUND: Pancreatic cystic lesions (PCL), including intraductal papillary mucinous neoplasia (IPMN), harbor different malignant potential and the optimal management is often challenging. The present study aims to depict the compliance of experts with current consensus guidelines and the accuracy of treatment recommendations stratified by the medical specialty and hospital volume. METHODS: An international survey was conducted using a set of 10 selected cases of PCL that were presented to a cohort of international experts on pancreatology. All presented cases were surgically resected between 2004 and 2015 and histopathological examination was available. Accuracy of the treatment recommendations was based on the European and international consensus guideline algorithms, and the histopathological result. RESULTS: The response rate of the survey was 26% (46 of 177 contacted experts), consisting of 70% surgeons and 30% gastroenterologists/oncologists (GI/Onc). In the case of main-duct IPMN (MD-IPMN), surgeons preferred more often the surgical approach in comparison with the GI/Onc (55 versus 44%). The mean accuracy rate based on the European and international consensus guidelines, and the histopathological result, were 71/76/38% (surgeons), and 70/73/34% (GI/Onc), respectively. High-volume centers achieved insignificantly higher accuracy scores with regard to the histopathology. Small branch-duct IPMN with cysts <2 cm and malignant potential were not identified by the guideline algorithms. CONCLUSION: The survey underlines the complexity of treatment decisions for patients with PCL; less than 40% of the recommendations were in line with the final histopathology in this selected case panel. Experts and consensus guidelines may fail to predict malignant potential in small PCL.

[Robotic Pancreatic Surgery]. / Roboterchirurgie des Pankreas.

Pancreatic surgery is one of the most challenging fields in visceral surgery. However, laparoscopic pancreatic surgery has not become the standard of care as yet, especially because of the very demanding reconstruction of anastomoses in pancreaticoduodenectomy. Robotic surgery has been a recent advance in laparoscopy. Its benefits are a better 3D view, a greater degree of freedom corresponding to that of the human hand, and tremor elimination. These factors greatly facilitate the intracorporeal suturing and knot-tying, which offers a technical advantage in performing pancreaticojejunostomy as compared with laparoscopic resections. However, only a few centres are offering this procedure for pancreatic resections. Retrospective analyses show that robotic pancreatic resections are safe und oncologically adequate if performed by experienced surgeons. Prospective, randomised trials comparing laparoscopic and robotic pancreatic resection techniques are not available to date.

[Total Pancreatectomy and Islet Autotransplantation in a Child with Recurrent Pancreatitis]. / Totale Pankreatektomie und Inselautotransplantation bei einem Kind mit chronisch rezidivierender Pankreatitis.

INTRODUCTION: Hereditary pancreatitis in children is rare. The indications for surgery in these children are complications and severe pain that cannot be managed by conservative treatment. Surgical treatment options are duodenum preserving resections as well as drainage procedures. Recurrences are common following theses surgical procedures, because usually the whole pancreas is affected. The majority of the children with symptomatic hereditary pancreatitis are free of pain after total pancreatectomy. When total pancreatectomy is combined with islet autotransplantation, pancreoprivic diabetes can be attenuated or even prevented. The principle of spleen-preserving total pancreatectomy combined with subsequent islet autotransplantation is shown in a case of a 10-year-old child with chronic recurrent pancreatitis in this video. INDICATION: Symptomatic chronic hereditary pancreatitis in children. PROCEDURE: Spleen-preserving total pancreatectomy, reconstruction with hepatico-jejunostomy and duodeno-jejunostomy, islet autotransplantation via portal vein. CONCLUSION: If the surgeon has appropriate experience, spleen-preserving total pancreatectomy is a safe procedure. In combination with islet autotransplantation, it may attenuate or prevent diabetes mellitus associated with total pancreatectomy. In highly selected pediatric patients, this surgical procedure has a major benefit compared to a purely symptomatic therapy.

Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study.

BACKGROUND: Circulating tumour cells (CTC) in the blood have been accepted as a prognostic marker in patients with metastatic colorectal cancer (CRC). Only limited data exist on the prognostic impact of CTC in patients with early stage CRC using standardised detection assays. The aim of this study was to elucidate the role of CTC in patients with non-metastatic CRC. METHODS: A total of 287 patients with potentially curable CRC were enrolled, including 239 patients with UICC stage I-III. CTC were measured in the blood using the CellSearch system preoperatively and on postoperative days 3 and 7. The complete patient group (UICC I-IV) and the non-metastatic cohort (UICC I-III) were analysed independently. Patients were followed for 28 (0-53) months. Prognostic factors for overall and progression-free survival were analysed using univariate and multivariate analyses. RESULTS: CTC were detected more frequently in patients with metastatic disease. No clinicopathological variables were associated with CTC detection in non-metastatic patients. CTC detection (⩾1 CTC per 7.5 ml blood) in the blood was significantly associated with worse overall survival (49.8 vs 38.4 months; P<0.001) in the non-metastatic group (UICC I-III), as well as in the complete cohort (48.4 vs 33.6 months; P<0.001). On multivariate analysis CTC were the strongest prognostic factor in non-metastatic patients (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.3-13.6) as well as in the entire study group (HR 5.6; 95% CI 2.6-12.0). CONCLUSIONS: Preoperative CTC detection is a strong and independent prognostic marker in non-metastatic CRC.

Islet transplantation at the Dresden diabetes center: five years' experience.

For the majority of patients with type 1 diabetes intensive insulin therapy is effective and safe for maintaining glycemia and minimizing diabetes-associated complications. However, a rare number of patients show highly labile metabolic control and experience repeated and unpredictable hypoglycemic episodes. Such condition is often caused by defective counterregulatory mechanisms and autonomous neuropathy. Patients are at high risk for severe acute and chronic complications, and quality of life is considerably impaired. For this small subset of patients, restoration of endogenous insulin secretion can substantially improve metabolic control and quality of life. In our experience, this is irrespective of insulin independency. Here, we report on our 5 years' experience with implementing islet transplantation as a potential treatment option for type 1 diabetes. All patients were treated by long-term insulin pump therapy prior to enrolment. The main indication was severely unstable diabetes and repeated hypoglycemia. From 2008 to 2013, 10 patients have been transplanted with single islet infusion; mean follow-up time was 35 months. All patients show persistent graft function, stable glycemic control with a reduction in HbA1c in the absence of hypoglycemia. All patients are kept on minimal exogenous insulin. In conclusion, islet transplantation can be an excellent therapy for selected patients. Key prerequisite for success is a strict indication. The primary goal for islet transplantation should be stabile glycemia and prevention of hypoglycemia rather than insulin independence. In fact, maintaining minimal exogenous insulin may protect the islet graft from metabolic stress and even prolong islet graft function.

Thrombosis: a major contributor to global disease burden.

BACKGROUND: Thrombosis is the common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused 1 in 4 deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. OBJECTIVE: To review the literature on the global burden of disease caused by VTE. APPROACH AND RESULTS: We performed a systematic review of the literature on the global disease burden because of VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥70 years. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years lost in low- and middle-income countries, and second in high-income countries, responsible for more disability-adjusted life-years lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. CONCLUSIONS: VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems and to evaluate whether improved use of preventive measures will reduce the burden.

[Appleby operation for locally advanced tumour of the pancreatic body and tail--a video demonstration]. / Appleby-Operation bei ausgedehntem Pankreaskorpus- und -schwanztumor - Video eines Falles.

INTRODUCTION: Patients with locally advanced pancreatic cancer and arterial infiltration of the coeliac artery are often classified as irresectable and therefore treated palliatively. For a highly selected group of patients, a complete resection (R0) of a pancreatic carcinoma including resection of the coeliac trunk without arterial reconstruction can mean a survival advantage. The expertise of the surgeon in vascular and pancreatic surgery as well as the proficiency of the entire surgical and anaesthesiological team and the appropriate infrastructure of the hospital are prerequisites for the success of such complex operations. Concerning the local finding of infiltration of the aorta, the gastroduodenal artery and the mesenteric superior artery should be excluded, to ensure R0 resection and perfusion of the liver via the gastroduodenal artery after resection. Moreover, the patient has to be fit for a large abdominal operation and extrapancreatic metastases have to be excluded, especially in ductal adenocarcinoma of the pancreas. In this video, the principles of the Appleby operation are shown in a case of locally advanced neuroendocrine carcinoma of the pancreas with infiltration of the coeliac artery. INDICATION: Locally advanced pancreatic neuroendocrine carcinoma with infiltration of the coeliac artery without distant metastasis after neoadjuvant therapy. PROCEDURE: Extended multiorgan pancreatic corpus and tail resection including resection of coeliac artery, portal vein resection, splenectomy, resection of left adrenal gland, subtotal gastrectomy and oversewing of the pancreatic head, end-to-end reconstruction of the portal vein and gastro-jejunostomy (Roux-Y) and duodeno-jejunostomy. CONCLUSION: Given the appropriate experience, the Appleby procedure is a technically demanding resection in pancreatic carcinomas involving the coeliac artery without arterial anastomosis. In selected cases this operation might have advantages compared to palliative treatment.

Tumour-site-dependent expression profile of angiogenic factors in tumour-associated stroma of primary colorectal cancer and metastases.

BACKGROUND: Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets. METHODS: Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay. RESULTS: We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases. CONCLUSION: Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer.

Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study).

BACKGROUND: Initially, unresectable colorectal liver metastases can be resected after response to chemotherapy. While cetuximab has been shown to increase response and resection rates, the survival outcome for this conversion strategy needs further evaluation. PATIENTS AND METHODS: Patients with technically unresectable and/or ≥5 liver metastases were treated with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated with regard to resectability every 2 months. Tumour response and secondary resection data have been reported previously. A final analysis of overall survival (OS) and progression-free survival (PFS) was carried out in December 2012. RESULTS: Between December 2004 and March 2008, 56 patients were randomised to arm A, 55 to arm B. The median OS was 35.7 [95% confidence interval (CI) 27.2-44.2] months [arm A: 35.8 (95% CI 28.1-43.6), arm B: 29.0 (95% CI 16.0-41.9) months, HR 1.03 (95% CI 0.66-1.61), P = 0.9]. The median PFS was 10.8 (95% CI 9.3-12.2) months [arm A: 11.2 (95% CI 7.2-15.3), arm B: 10.5 (95% CI 8.9-12.2) months, HR 1.18 (95% CI 0.79-1.74), P = 0.4]. Patients who underwent R0 resection (n = 36) achieved a better median OS [53.9 (95% CI 35.9-71.9) months] than those who did not [21.9 (95% CI 17.1-26.7) months, P < 0.001]. The median disease-free survival for R0 resected patients was 9.9 (95% CI 5.8-14.0) months, and the 5-year OS rate was 46.2% (95% CI 29.5% to 62.9%). CONCLUSIONS: This study confirms a favourable long-term survival for patients with initially sub-optimal or unresectable colorectal liver metastases who respond to conversion therapy and undergo secondary resection. Both FOLFOX/FOLFIRI plus cetuximab, appear to be appropriate regimens for 'conversion' treatment in patients with K-RAS codon 12/13/61 wild-type tumours. Thus, liver surgery can be considered curative or alternatively as an additional 'line of therapy' in those patients who are not cured. CLINICAL TRIAL NUMBER: NCT00153998, www.clinicaltrials.gov.

Randomized clinical trial of stapler versus clamp-crushing transection in elective liver resection.

BACKGROUND: Various devices have been developed to facilitate liver transection and reduce blood loss in liver resections. None of these has proven superiority compared with the classical clamp-crushing technique. This randomized clinical trial compared the effectiveness and safety of stapler transection with that of clamp-crushing during open liver resection. METHODS: Patients admitted for elective open liver resection between January 2010 and October 2011 were assigned randomly to stapler transection or the clamp-crushing technique. The primary endpoint was the total amount of intraoperative blood loss. Secondary endpoints included transection time, duration of operation, complication rates and resection margins. RESULTS: A total of 130 patients were enrolled, 65 to clamp-crushing and 65 to stapler transection. There was no difference between groups in total intraoperative blood loss: median (i.q.r.) 1050 (525-1650) versus 925 (450-1425) ml respectively (P = 0·279). The difference in total intraoperative blood loss normalized to the transection surface area was not statistically significant (P = 0·092). Blood loss during parenchymal transection was significantly lower in the stapler transection group (P = 0·002), as were the parenchymal transection time (mean(s.d.) 30(21) versus 9(7) min for clamp-crushing and stapler transection groups respectively; P < 0·001) and total duration of operation (mean(s.d.) 221(86) versus 190(85) min; P = 0·047). There were no significant differences in postoperative morbidity (P = 0·863) or mortality (P = 0·684) between groups. CONCLUSION: Stapler transection is a safe technique but does not reduce intraoperative blood loss in elective liver resection compared with the clamp-crushing technique. REGISTRATION NUMBER: NCT01049607 (http://www.clinicaltrials.gov).

Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities.

PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity METHODS: A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. RESULTS: Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION: Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.

[Nerve-preserving low anterior rectum resection]. / Nervenschonende offene tiefe anteriore Rektumresektion beim Rektumkarzinom.

AIM: The Performance of an oncological low anterior rectum resection with preservation of the sympathic and parasympathic nerves is illustrated. INDICATION: The total mesorectal excision (TME) by Robert Heald et al. is the gold standard for rectal cancer operations which has lowered drastically the local recurrence rate. As the survival data improve, the new focus is the postoperative quality of life with preserving of the bladder and sexual function. METHOD: We demonstrate an anterior rectal cancer operation with preserving of the sympathetic and parasympathetic nerves step by step. CONCLUSION: The critical parts of preserving the nerves with the N. hypogastricus superior and inferior as well as the neurovascular bundle "erigent pillar" are demonstrated.